anno_start	anno_end	anno_text	entity_type	sentence	section
21	55	JNK/p38-specific MAPK phosphatases	protein_type	A conserved motif in JNK/p38-specific MAPK phosphatases as a determinant for JNK1 recognition and inactivation	TITLE
77	81	JNK1	protein	A conserved motif in JNK/p38-specific MAPK phosphatases as a determinant for JNK1 recognition and inactivation	TITLE
0	33	Mitogen-activated protein kinases	protein_type	Mitogen-activated protein kinases (MAPKs), important in a large array of signalling pathways, are tightly controlled by a cascade of protein kinases and by MAPK phosphatases (MKPs).	ABSTRACT
35	40	MAPKs	protein_type	Mitogen-activated protein kinases (MAPKs), important in a large array of signalling pathways, are tightly controlled by a cascade of protein kinases and by MAPK phosphatases (MKPs).	ABSTRACT
133	148	protein kinases	protein_type	Mitogen-activated protein kinases (MAPKs), important in a large array of signalling pathways, are tightly controlled by a cascade of protein kinases and by MAPK phosphatases (MKPs).	ABSTRACT
156	173	MAPK phosphatases	protein_type	Mitogen-activated protein kinases (MAPKs), important in a large array of signalling pathways, are tightly controlled by a cascade of protein kinases and by MAPK phosphatases (MKPs).	ABSTRACT
175	179	MKPs	protein_type	Mitogen-activated protein kinases (MAPKs), important in a large array of signalling pathways, are tightly controlled by a cascade of protein kinases and by MAPK phosphatases (MKPs).	ABSTRACT
0	4	MAPK	protein_type	MAPK signalling efficiency and specificity is modulated by protein–protein interactions between individual MAPKs and the docking motifs in cognate binding partners.	ABSTRACT
107	112	MAPKs	protein_type	MAPK signalling efficiency and specificity is modulated by protein–protein interactions between individual MAPKs and the docking motifs in cognate binding partners.	ABSTRACT
121	135	docking motifs	structure_element	MAPK signalling efficiency and specificity is modulated by protein–protein interactions between individual MAPKs and the docking motifs in cognate binding partners.	ABSTRACT
56	63	D-motif	structure_element	Two types of docking interactions have been identified: D-motif-mediated interaction and FXF-docking interaction.	ABSTRACT
89	112	FXF-docking interaction	site	Two types of docking interactions have been identified: D-motif-mediated interaction and FXF-docking interaction.	ABSTRACT
19	36	crystal structure	evidence	Here we report the crystal structure of JNK1 bound to the catalytic domain of MKP7 at 2.4-Å resolution, providing high-resolution structural insight into the FXF-docking interaction.	ABSTRACT
40	44	JNK1	protein	Here we report the crystal structure of JNK1 bound to the catalytic domain of MKP7 at 2.4-Å resolution, providing high-resolution structural insight into the FXF-docking interaction.	ABSTRACT
45	53	bound to	protein_state	Here we report the crystal structure of JNK1 bound to the catalytic domain of MKP7 at 2.4-Å resolution, providing high-resolution structural insight into the FXF-docking interaction.	ABSTRACT
58	74	catalytic domain	structure_element	Here we report the crystal structure of JNK1 bound to the catalytic domain of MKP7 at 2.4-Å resolution, providing high-resolution structural insight into the FXF-docking interaction.	ABSTRACT
78	82	MKP7	protein	Here we report the crystal structure of JNK1 bound to the catalytic domain of MKP7 at 2.4-Å resolution, providing high-resolution structural insight into the FXF-docking interaction.	ABSTRACT
158	181	FXF-docking interaction	site	Here we report the crystal structure of JNK1 bound to the catalytic domain of MKP7 at 2.4-Å resolution, providing high-resolution structural insight into the FXF-docking interaction.	ABSTRACT
4	22	285FNFL288 segment	structure_element	The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.	ABSTRACT
26	30	MKP7	protein	The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.	ABSTRACT
51	67	hydrophobic site	site	The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.	ABSTRACT
71	75	JNK1	protein	The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.	ABSTRACT
93	97	MAPK	protein_type	The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.	ABSTRACT
112	117	helix	structure_element	The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.	ABSTRACT
118	120	αG	structure_element	The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.	ABSTRACT
122	141	Biochemical studies	experimental_method	The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.	ABSTRACT
167	183	highly conserved	protein_state	The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.	ABSTRACT
184	200	structural motif	structure_element	The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.	ABSTRACT
234	244	MKP family	protein_type	The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.	ABSTRACT
305	308	MKP	protein_type	The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.	ABSTRACT
309	313	MAPK	protein_type	The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.	ABSTRACT
15	26	MAPK family	protein_type	 The important MAPK family of signalling proteins is controlled by MAPK phosphatases (MKPs).	ABSTRACT
67	84	MAPK phosphatases	protein_type	 The important MAPK family of signalling proteins is controlled by MAPK phosphatases (MKPs).	ABSTRACT
86	90	MKPs	protein_type	 The important MAPK family of signalling proteins is controlled by MAPK phosphatases (MKPs).	ABSTRACT
29	38	structure	evidence	Here, the authors report the structure of MKP7 bound to JNK1 and characterise the conserved MKP-MAPK interaction.	ABSTRACT
42	46	MKP7	protein	Here, the authors report the structure of MKP7 bound to JNK1 and characterise the conserved MKP-MAPK interaction.	ABSTRACT
47	55	bound to	protein_state	Here, the authors report the structure of MKP7 bound to JNK1 and characterise the conserved MKP-MAPK interaction.	ABSTRACT
56	60	JNK1	protein	Here, the authors report the structure of MKP7 bound to JNK1 and characterise the conserved MKP-MAPK interaction.	ABSTRACT
82	91	conserved	protein_state	Here, the authors report the structure of MKP7 bound to JNK1 and characterise the conserved MKP-MAPK interaction.	ABSTRACT
92	95	MKP	protein_type	Here, the authors report the structure of MKP7 bound to JNK1 and characterise the conserved MKP-MAPK interaction.	ABSTRACT
96	100	MAPK	protein_type	Here, the authors report the structure of MKP7 bound to JNK1 and characterise the conserved MKP-MAPK interaction.	ABSTRACT
4	37	mitogen-activated protein kinases	protein_type	The mitogen-activated protein kinases (MAPKs) are central components of the signal-transduction pathways, which mediate the cellular response to a variety of extracellular stimuli, ranging from growth factors to environmental stresses.	INTRO
39	44	MAPKs	protein_type	The mitogen-activated protein kinases (MAPKs) are central components of the signal-transduction pathways, which mediate the cellular response to a variety of extracellular stimuli, ranging from growth factors to environmental stresses.	INTRO
4	8	MAPK	protein_type	The MAPK signalling pathways are evolutionally highly conserved.	INTRO
22	26	MAPK	protein_type	The basic assembly of MAPK pathways is a three-tier kinase module that establishes a sequential activation cascade: a MAPK kinase kinase activates a MAPK kinase, which in turn activates a MAPK.	INTRO
52	58	kinase	protein_type	The basic assembly of MAPK pathways is a three-tier kinase module that establishes a sequential activation cascade: a MAPK kinase kinase activates a MAPK kinase, which in turn activates a MAPK.	INTRO
118	136	MAPK kinase kinase	protein_type	The basic assembly of MAPK pathways is a three-tier kinase module that establishes a sequential activation cascade: a MAPK kinase kinase activates a MAPK kinase, which in turn activates a MAPK.	INTRO
149	160	MAPK kinase	protein_type	The basic assembly of MAPK pathways is a three-tier kinase module that establishes a sequential activation cascade: a MAPK kinase kinase activates a MAPK kinase, which in turn activates a MAPK.	INTRO
188	192	MAPK	protein_type	The basic assembly of MAPK pathways is a three-tier kinase module that establishes a sequential activation cascade: a MAPK kinase kinase activates a MAPK kinase, which in turn activates a MAPK.	INTRO
29	33	MAPK	protein_type	The three best-characterized MAPK signalling pathways are mediated by the kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38.	INTRO
74	81	kinases	protein_type	The three best-characterized MAPK signalling pathways are mediated by the kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38.	INTRO
82	119	extracellular signal-regulated kinase	protein_type	The three best-characterized MAPK signalling pathways are mediated by the kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38.	INTRO
121	124	ERK	protein_type	The three best-characterized MAPK signalling pathways are mediated by the kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38.	INTRO
127	150	c-Jun N-terminal kinase	protein_type	The three best-characterized MAPK signalling pathways are mediated by the kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38.	INTRO
152	155	JNK	protein_type	The three best-characterized MAPK signalling pathways are mediated by the kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38.	INTRO
161	164	p38	protein_type	The three best-characterized MAPK signalling pathways are mediated by the kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38.	INTRO
4	7	ERK	protein_type	The ERK pathway is activated by various mitogens and phorbol esters, whereas the JNK and p38 pathways are stimulated mainly by environmental stress and inflammatory cytokines.	INTRO
81	84	JNK	protein_type	The ERK pathway is activated by various mitogens and phorbol esters, whereas the JNK and p38 pathways are stimulated mainly by environmental stress and inflammatory cytokines.	INTRO
89	92	p38	protein_type	The ERK pathway is activated by various mitogens and phorbol esters, whereas the JNK and p38 pathways are stimulated mainly by environmental stress and inflammatory cytokines.	INTRO
165	174	cytokines	protein_type	The ERK pathway is activated by various mitogens and phorbol esters, whereas the JNK and p38 pathways are stimulated mainly by environmental stress and inflammatory cytokines.	INTRO
4	9	MAPKs	protein_type	The MAPKs are activated by MAPK kinases that phosphorylate the MAPKs at conserved threonine and tyrosine residues within their activation loop.	INTRO
27	39	MAPK kinases	protein_type	The MAPKs are activated by MAPK kinases that phosphorylate the MAPKs at conserved threonine and tyrosine residues within their activation loop.	INTRO
63	68	MAPKs	protein_type	The MAPKs are activated by MAPK kinases that phosphorylate the MAPKs at conserved threonine and tyrosine residues within their activation loop.	INTRO
72	81	conserved	protein_state	The MAPKs are activated by MAPK kinases that phosphorylate the MAPKs at conserved threonine and tyrosine residues within their activation loop.	INTRO
82	91	threonine	residue_name	The MAPKs are activated by MAPK kinases that phosphorylate the MAPKs at conserved threonine and tyrosine residues within their activation loop.	INTRO
96	104	tyrosine	residue_name	The MAPKs are activated by MAPK kinases that phosphorylate the MAPKs at conserved threonine and tyrosine residues within their activation loop.	INTRO
127	142	activation loop	structure_element	The MAPKs are activated by MAPK kinases that phosphorylate the MAPKs at conserved threonine and tyrosine residues within their activation loop.	INTRO
23	27	MAPK	protein_type	After activation, each MAPK phosphorylates a distinct set of protein substrates, which act as the critical effectors that enable cells to mount the appropriate responses to varied stimuli.	INTRO
0	5	MAPKs	protein_type	MAPKs lie at the bottom of conserved three-component phosphorylation cascades and utilize docking interactions to link module components and bind substrates.	INTRO
13	27	docking motifs	structure_element	Two types of docking motifs have been identified in MAPK substrates and cognate proteins: kinase-interacting motif (D-motif) and FXF-motif (also called DEF motif, docking site for ERK FXF).	INTRO
52	56	MAPK	protein_type	Two types of docking motifs have been identified in MAPK substrates and cognate proteins: kinase-interacting motif (D-motif) and FXF-motif (also called DEF motif, docking site for ERK FXF).	INTRO
90	114	kinase-interacting motif	structure_element	Two types of docking motifs have been identified in MAPK substrates and cognate proteins: kinase-interacting motif (D-motif) and FXF-motif (also called DEF motif, docking site for ERK FXF).	INTRO
116	123	D-motif	structure_element	Two types of docking motifs have been identified in MAPK substrates and cognate proteins: kinase-interacting motif (D-motif) and FXF-motif (also called DEF motif, docking site for ERK FXF).	INTRO
129	138	FXF-motif	structure_element	Two types of docking motifs have been identified in MAPK substrates and cognate proteins: kinase-interacting motif (D-motif) and FXF-motif (also called DEF motif, docking site for ERK FXF).	INTRO
152	161	DEF motif	structure_element	Two types of docking motifs have been identified in MAPK substrates and cognate proteins: kinase-interacting motif (D-motif) and FXF-motif (also called DEF motif, docking site for ERK FXF).	INTRO
163	175	docking site	site	Two types of docking motifs have been identified in MAPK substrates and cognate proteins: kinase-interacting motif (D-motif) and FXF-motif (also called DEF motif, docking site for ERK FXF).	INTRO
180	183	ERK	protein_type	Two types of docking motifs have been identified in MAPK substrates and cognate proteins: kinase-interacting motif (D-motif) and FXF-motif (also called DEF motif, docking site for ERK FXF).	INTRO
184	187	FXF	structure_element	Two types of docking motifs have been identified in MAPK substrates and cognate proteins: kinase-interacting motif (D-motif) and FXF-motif (also called DEF motif, docking site for ERK FXF).	INTRO
56	67	MAP kinases	protein_type	The best-studied docking interactions are those between MAP kinases and ‘D-motifs', which consists of two or more basic residues followed by a short linker and a cluster of hydrophobic residues.	INTRO
73	81	D-motifs	structure_element	The best-studied docking interactions are those between MAP kinases and ‘D-motifs', which consists of two or more basic residues followed by a short linker and a cluster of hydrophobic residues.	INTRO
143	155	short linker	structure_element	The best-studied docking interactions are those between MAP kinases and ‘D-motifs', which consists of two or more basic residues followed by a short linker and a cluster of hydrophobic residues.	INTRO
4	24	D-motif-docking site	site	The D-motif-docking site (D-site) in MAPKs is situated in a noncatalytic region opposite of the kinase catalytic pocket and is comprised of a highly acidic patch and a hydrophobic groove.	INTRO
26	32	D-site	site	The D-motif-docking site (D-site) in MAPKs is situated in a noncatalytic region opposite of the kinase catalytic pocket and is comprised of a highly acidic patch and a hydrophobic groove.	INTRO
37	42	MAPKs	protein_type	The D-motif-docking site (D-site) in MAPKs is situated in a noncatalytic region opposite of the kinase catalytic pocket and is comprised of a highly acidic patch and a hydrophobic groove.	INTRO
60	79	noncatalytic region	site	The D-motif-docking site (D-site) in MAPKs is situated in a noncatalytic region opposite of the kinase catalytic pocket and is comprised of a highly acidic patch and a hydrophobic groove.	INTRO
96	102	kinase	protein_type	The D-motif-docking site (D-site) in MAPKs is situated in a noncatalytic region opposite of the kinase catalytic pocket and is comprised of a highly acidic patch and a hydrophobic groove.	INTRO
103	119	catalytic pocket	site	The D-motif-docking site (D-site) in MAPKs is situated in a noncatalytic region opposite of the kinase catalytic pocket and is comprised of a highly acidic patch and a hydrophobic groove.	INTRO
142	161	highly acidic patch	site	The D-motif-docking site (D-site) in MAPKs is situated in a noncatalytic region opposite of the kinase catalytic pocket and is comprised of a highly acidic patch and a hydrophobic groove.	INTRO
168	186	hydrophobic groove	site	The D-motif-docking site (D-site) in MAPKs is situated in a noncatalytic region opposite of the kinase catalytic pocket and is comprised of a highly acidic patch and a hydrophobic groove.	INTRO
0	8	D-motifs	structure_element	D-motifs are found in many MAPK-interacting proteins, including substrates, activating kinases and inactivating phosphatases, as well as scaffolding proteins.	INTRO
27	52	MAPK-interacting proteins	protein_type	D-motifs are found in many MAPK-interacting proteins, including substrates, activating kinases and inactivating phosphatases, as well as scaffolding proteins.	INTRO
87	94	kinases	protein_type	D-motifs are found in many MAPK-interacting proteins, including substrates, activating kinases and inactivating phosphatases, as well as scaffolding proteins.	INTRO
112	124	phosphatases	protein_type	D-motifs are found in many MAPK-interacting proteins, including substrates, activating kinases and inactivating phosphatases, as well as scaffolding proteins.	INTRO
2	22	second docking motif	structure_element	A second docking motif for MAPKs consists of two Phe residues separated by one residue (FXF-motif).	INTRO
27	32	MAPKs	protein_type	A second docking motif for MAPKs consists of two Phe residues separated by one residue (FXF-motif).	INTRO
49	52	Phe	residue_name	A second docking motif for MAPKs consists of two Phe residues separated by one residue (FXF-motif).	INTRO
88	97	FXF-motif	structure_element	A second docking motif for MAPKs consists of two Phe residues separated by one residue (FXF-motif).	INTRO
40	44	MAPK	protein_type	This motif has been observed in several MAPK substrates.	INTRO
4	26	FXF-motif-binding site	site	The FXF-motif-binding site of ERK2 has been mapped to a hydrophobic pocket formed between the P+1 site, αG helix and the MAPK insert.	INTRO
30	34	ERK2	protein	The FXF-motif-binding site of ERK2 has been mapped to a hydrophobic pocket formed between the P+1 site, αG helix and the MAPK insert.	INTRO
56	74	hydrophobic pocket	site	The FXF-motif-binding site of ERK2 has been mapped to a hydrophobic pocket formed between the P+1 site, αG helix and the MAPK insert.	INTRO
94	102	P+1 site	site	The FXF-motif-binding site of ERK2 has been mapped to a hydrophobic pocket formed between the P+1 site, αG helix and the MAPK insert.	INTRO
104	112	αG helix	structure_element	The FXF-motif-binding site of ERK2 has been mapped to a hydrophobic pocket formed between the P+1 site, αG helix and the MAPK insert.	INTRO
121	132	MAPK insert	structure_element	The FXF-motif-binding site of ERK2 has been mapped to a hydrophobic pocket formed between the P+1 site, αG helix and the MAPK insert.	INTRO
45	48	FXF	structure_element	However, the generality and mechanism of the FXF-mediated interaction is unclear.	INTRO
29	33	MAPK	protein_type	The physiological outcome of MAPK signalling depends on both the magnitude and the duration of kinase activation.	INTRO
18	22	MAPK	protein_type	Downregulation of MAPK activity can be achieved through direct dephosphorylation of the phospho-threonine and/or tyrosine residues by various serine/threonine phosphatases, tyrosine phosphatases and dual-specificity phosphatases (DUSPs) termed MKPs.	INTRO
88	121	phospho-threonine and/or tyrosine	residue_name	Downregulation of MAPK activity can be achieved through direct dephosphorylation of the phospho-threonine and/or tyrosine residues by various serine/threonine phosphatases, tyrosine phosphatases and dual-specificity phosphatases (DUSPs) termed MKPs.	INTRO
142	171	serine/threonine phosphatases	protein_type	Downregulation of MAPK activity can be achieved through direct dephosphorylation of the phospho-threonine and/or tyrosine residues by various serine/threonine phosphatases, tyrosine phosphatases and dual-specificity phosphatases (DUSPs) termed MKPs.	INTRO
173	194	tyrosine phosphatases	protein_type	Downregulation of MAPK activity can be achieved through direct dephosphorylation of the phospho-threonine and/or tyrosine residues by various serine/threonine phosphatases, tyrosine phosphatases and dual-specificity phosphatases (DUSPs) termed MKPs.	INTRO
199	228	dual-specificity phosphatases	protein_type	Downregulation of MAPK activity can be achieved through direct dephosphorylation of the phospho-threonine and/or tyrosine residues by various serine/threonine phosphatases, tyrosine phosphatases and dual-specificity phosphatases (DUSPs) termed MKPs.	INTRO
230	235	DUSPs	protein_type	Downregulation of MAPK activity can be achieved through direct dephosphorylation of the phospho-threonine and/or tyrosine residues by various serine/threonine phosphatases, tyrosine phosphatases and dual-specificity phosphatases (DUSPs) termed MKPs.	INTRO
244	248	MKPs	protein_type	Downregulation of MAPK activity can be achieved through direct dephosphorylation of the phospho-threonine and/or tyrosine residues by various serine/threonine phosphatases, tyrosine phosphatases and dual-specificity phosphatases (DUSPs) termed MKPs.	INTRO
0	4	MKPs	protein_type	MKPs constitute a group of DUSPs that are characterized by their ability to dephosphorylate both phosphotyrosine and phosphoserine/phospho-threonine residues within a substrate.	INTRO
27	32	DUSPs	protein_type	MKPs constitute a group of DUSPs that are characterized by their ability to dephosphorylate both phosphotyrosine and phosphoserine/phospho-threonine residues within a substrate.	INTRO
97	112	phosphotyrosine	residue_name	MKPs constitute a group of DUSPs that are characterized by their ability to dephosphorylate both phosphotyrosine and phosphoserine/phospho-threonine residues within a substrate.	INTRO
117	130	phosphoserine	residue_name	MKPs constitute a group of DUSPs that are characterized by their ability to dephosphorylate both phosphotyrosine and phosphoserine/phospho-threonine residues within a substrate.	INTRO
131	148	phospho-threonine	residue_name	MKPs constitute a group of DUSPs that are characterized by their ability to dephosphorylate both phosphotyrosine and phosphoserine/phospho-threonine residues within a substrate.	INTRO
27	31	MKPs	protein_type	Dysregulated expression of MKPs has been associated with pathogenesis of various diseases, and understanding their precise recognition mechanism presents an important challenge and opportunity for drug development.	INTRO
21	38	crystal structure	evidence	Here, we present the crystal structure of JNK1 in complex with the catalytic domain of MKP7.	INTRO
42	46	JNK1	protein	Here, we present the crystal structure of JNK1 in complex with the catalytic domain of MKP7.	INTRO
47	62	in complex with	protein_state	Here, we present the crystal structure of JNK1 in complex with the catalytic domain of MKP7.	INTRO
67	83	catalytic domain	structure_element	Here, we present the crystal structure of JNK1 in complex with the catalytic domain of MKP7.	INTRO
87	91	MKP7	protein	Here, we present the crystal structure of JNK1 in complex with the catalytic domain of MKP7.	INTRO
5	14	structure	evidence	This structure reveals the molecular mechanism underlying the docking interaction between MKP7 and JNK1.	INTRO
90	94	MKP7	protein	This structure reveals the molecular mechanism underlying the docking interaction between MKP7 and JNK1.	INTRO
99	103	JNK1	protein	This structure reveals the molecular mechanism underlying the docking interaction between MKP7 and JNK1.	INTRO
7	16	JNK1–MKP7	complex_assembly	In the JNK1–MKP7 complex, a hydrophobic motif (285FNFL288) that initiates the helix α5 in the MKP7 catalytic domain directly binds to the FXF-motif-binding site on JNK1, providing the structural insight into the classic FXF-type docking interaction.	INTRO
28	45	hydrophobic motif	structure_element	In the JNK1–MKP7 complex, a hydrophobic motif (285FNFL288) that initiates the helix α5 in the MKP7 catalytic domain directly binds to the FXF-motif-binding site on JNK1, providing the structural insight into the classic FXF-type docking interaction.	INTRO
47	57	285FNFL288	structure_element	In the JNK1–MKP7 complex, a hydrophobic motif (285FNFL288) that initiates the helix α5 in the MKP7 catalytic domain directly binds to the FXF-motif-binding site on JNK1, providing the structural insight into the classic FXF-type docking interaction.	INTRO
78	83	helix	structure_element	In the JNK1–MKP7 complex, a hydrophobic motif (285FNFL288) that initiates the helix α5 in the MKP7 catalytic domain directly binds to the FXF-motif-binding site on JNK1, providing the structural insight into the classic FXF-type docking interaction.	INTRO
84	86	α5	structure_element	In the JNK1–MKP7 complex, a hydrophobic motif (285FNFL288) that initiates the helix α5 in the MKP7 catalytic domain directly binds to the FXF-motif-binding site on JNK1, providing the structural insight into the classic FXF-type docking interaction.	INTRO
94	98	MKP7	protein	In the JNK1–MKP7 complex, a hydrophobic motif (285FNFL288) that initiates the helix α5 in the MKP7 catalytic domain directly binds to the FXF-motif-binding site on JNK1, providing the structural insight into the classic FXF-type docking interaction.	INTRO
99	115	catalytic domain	structure_element	In the JNK1–MKP7 complex, a hydrophobic motif (285FNFL288) that initiates the helix α5 in the MKP7 catalytic domain directly binds to the FXF-motif-binding site on JNK1, providing the structural insight into the classic FXF-type docking interaction.	INTRO
138	160	FXF-motif-binding site	site	In the JNK1–MKP7 complex, a hydrophobic motif (285FNFL288) that initiates the helix α5 in the MKP7 catalytic domain directly binds to the FXF-motif-binding site on JNK1, providing the structural insight into the classic FXF-type docking interaction.	INTRO
164	168	JNK1	protein	In the JNK1–MKP7 complex, a hydrophobic motif (285FNFL288) that initiates the helix α5 in the MKP7 catalytic domain directly binds to the FXF-motif-binding site on JNK1, providing the structural insight into the classic FXF-type docking interaction.	INTRO
220	248	FXF-type docking interaction	site	In the JNK1–MKP7 complex, a hydrophobic motif (285FNFL288) that initiates the helix α5 in the MKP7 catalytic domain directly binds to the FXF-motif-binding site on JNK1, providing the structural insight into the classic FXF-type docking interaction.	INTRO
0	33	Biochemical and modelling studies	experimental_method	Biochemical and modelling studies further demonstrate that the molecular interactions mediate this key element for substrate recognition are highly conserved among all MKP-family members.	INTRO
168	186	MKP-family members	protein_type	Biochemical and modelling studies further demonstrate that the molecular interactions mediate this key element for substrate recognition are highly conserved among all MKP-family members.	INTRO
111	124	MAPK isoforms	protein_type	Thus, our study reveals a hitherto unrecognized interaction mode for encoding complex target specificity among MAPK isoforms.	INTRO
15	19	JNK1	protein	Interaction of JNK1 with the MKP7 catalytic domain	RESULTS
29	33	MKP7	protein	Interaction of JNK1 with the MKP7 catalytic domain	RESULTS
34	50	catalytic domain	structure_element	Interaction of JNK1 with the MKP7 catalytic domain	RESULTS
0	5	DUSPs	protein_type	DUSPs belong to the protein-tyrosine phosphatases (PTPase) superfamily, which is defined by the PTPase-signature motif CXXGXXR.	RESULTS
20	49	protein-tyrosine phosphatases	protein_type	DUSPs belong to the protein-tyrosine phosphatases (PTPase) superfamily, which is defined by the PTPase-signature motif CXXGXXR.	RESULTS
51	57	PTPase	protein_type	DUSPs belong to the protein-tyrosine phosphatases (PTPase) superfamily, which is defined by the PTPase-signature motif CXXGXXR.	RESULTS
96	102	PTPase	protein_type	DUSPs belong to the protein-tyrosine phosphatases (PTPase) superfamily, which is defined by the PTPase-signature motif CXXGXXR.	RESULTS
119	126	CXXGXXR	structure_element	DUSPs belong to the protein-tyrosine phosphatases (PTPase) superfamily, which is defined by the PTPase-signature motif CXXGXXR.	RESULTS
0	4	MKPs	protein_type	MKPs represent a distinct subfamily within a larger group of DUSPs.	RESULTS
61	66	DUSPs	protein_type	MKPs represent a distinct subfamily within a larger group of DUSPs.	RESULTS
3	12	mammalian	taxonomy_domain	In mammalian cells, the MKP subfamily includes 10 distinct catalytically active MKPs.	RESULTS
24	37	MKP subfamily	protein_type	In mammalian cells, the MKP subfamily includes 10 distinct catalytically active MKPs.	RESULTS
59	79	catalytically active	protein_state	In mammalian cells, the MKP subfamily includes 10 distinct catalytically active MKPs.	RESULTS
80	84	MKPs	protein_type	In mammalian cells, the MKP subfamily includes 10 distinct catalytically active MKPs.	RESULTS
4	8	MKPs	protein_type	All MKPs contain a highly conserved C-terminal catalytic domain (CD) and an N-terminal kinase-binding domain (KBD).	RESULTS
19	35	highly conserved	protein_state	All MKPs contain a highly conserved C-terminal catalytic domain (CD) and an N-terminal kinase-binding domain (KBD).	RESULTS
47	63	catalytic domain	structure_element	All MKPs contain a highly conserved C-terminal catalytic domain (CD) and an N-terminal kinase-binding domain (KBD).	RESULTS
65	67	CD	structure_element	All MKPs contain a highly conserved C-terminal catalytic domain (CD) and an N-terminal kinase-binding domain (KBD).	RESULTS
87	108	kinase-binding domain	structure_element	All MKPs contain a highly conserved C-terminal catalytic domain (CD) and an N-terminal kinase-binding domain (KBD).	RESULTS
110	113	KBD	structure_element	All MKPs contain a highly conserved C-terminal catalytic domain (CD) and an N-terminal kinase-binding domain (KBD).	RESULTS
4	7	KBD	structure_element	The KBD is homologous to the rhodanese family and contains an intervening cluster of basic amino acids, which has been suggested to be important for interacting with the target MAPKs.	RESULTS
29	45	rhodanese family	protein_type	The KBD is homologous to the rhodanese family and contains an intervening cluster of basic amino acids, which has been suggested to be important for interacting with the target MAPKs.	RESULTS
177	182	MAPKs	protein_type	The KBD is homologous to the rhodanese family and contains an intervening cluster of basic amino acids, which has been suggested to be important for interacting with the target MAPKs.	RESULTS
105	115	MKP family	protein_type	On the basis of sequence similarity, substrate specificity and predominant subcellular localization, the MKP family can be further divided into three groups (Fig. 1).	RESULTS
0	34	Biochemical and structural studies	experimental_method	Biochemical and structural studies have revealed that the KBD of MKPs is critical for MKP3 docking to ERK2, and MKP5 binding to p38α, although their binding mechanisms are completely different.	RESULTS
58	61	KBD	structure_element	Biochemical and structural studies have revealed that the KBD of MKPs is critical for MKP3 docking to ERK2, and MKP5 binding to p38α, although their binding mechanisms are completely different.	RESULTS
65	69	MKPs	protein_type	Biochemical and structural studies have revealed that the KBD of MKPs is critical for MKP3 docking to ERK2, and MKP5 binding to p38α, although their binding mechanisms are completely different.	RESULTS
86	90	MKP3	protein	Biochemical and structural studies have revealed that the KBD of MKPs is critical for MKP3 docking to ERK2, and MKP5 binding to p38α, although their binding mechanisms are completely different.	RESULTS
102	106	ERK2	protein	Biochemical and structural studies have revealed that the KBD of MKPs is critical for MKP3 docking to ERK2, and MKP5 binding to p38α, although their binding mechanisms are completely different.	RESULTS
112	116	MKP5	protein	Biochemical and structural studies have revealed that the KBD of MKPs is critical for MKP3 docking to ERK2, and MKP5 binding to p38α, although their binding mechanisms are completely different.	RESULTS
128	132	p38α	protein	Biochemical and structural studies have revealed that the KBD of MKPs is critical for MKP3 docking to ERK2, and MKP5 binding to p38α, although their binding mechanisms are completely different.	RESULTS
32	37	MAPKs	protein_type	However, it is unknown if other MAPKs can interact with the KBD of their cognate phosphatases in the same manner as observed for recognition of ERK2 and p38α by their MKPs, or whether they recognize distinct docking motifs of MKPs.	RESULTS
60	63	KBD	structure_element	However, it is unknown if other MAPKs can interact with the KBD of their cognate phosphatases in the same manner as observed for recognition of ERK2 and p38α by their MKPs, or whether they recognize distinct docking motifs of MKPs.	RESULTS
81	93	phosphatases	protein_type	However, it is unknown if other MAPKs can interact with the KBD of their cognate phosphatases in the same manner as observed for recognition of ERK2 and p38α by their MKPs, or whether they recognize distinct docking motifs of MKPs.	RESULTS
144	148	ERK2	protein	However, it is unknown if other MAPKs can interact with the KBD of their cognate phosphatases in the same manner as observed for recognition of ERK2 and p38α by their MKPs, or whether they recognize distinct docking motifs of MKPs.	RESULTS
153	157	p38α	protein	However, it is unknown if other MAPKs can interact with the KBD of their cognate phosphatases in the same manner as observed for recognition of ERK2 and p38α by their MKPs, or whether they recognize distinct docking motifs of MKPs.	RESULTS
167	171	MKPs	protein_type	However, it is unknown if other MAPKs can interact with the KBD of their cognate phosphatases in the same manner as observed for recognition of ERK2 and p38α by their MKPs, or whether they recognize distinct docking motifs of MKPs.	RESULTS
208	222	docking motifs	structure_element	However, it is unknown if other MAPKs can interact with the KBD of their cognate phosphatases in the same manner as observed for recognition of ERK2 and p38α by their MKPs, or whether they recognize distinct docking motifs of MKPs.	RESULTS
226	230	MKPs	protein_type	However, it is unknown if other MAPKs can interact with the KBD of their cognate phosphatases in the same manner as observed for recognition of ERK2 and p38α by their MKPs, or whether they recognize distinct docking motifs of MKPs.	RESULTS
0	4	MKP7	protein	MKP7, the biggest molecule in the MKP family, selectively inactivates JNK and p38 following stress activation.	RESULTS
34	44	MKP family	protein_type	MKP7, the biggest molecule in the MKP family, selectively inactivates JNK and p38 following stress activation.	RESULTS
70	73	JNK	protein_type	MKP7, the biggest molecule in the MKP family, selectively inactivates JNK and p38 following stress activation.	RESULTS
78	81	p38	protein_type	MKP7, the biggest molecule in the MKP family, selectively inactivates JNK and p38 following stress activation.	RESULTS
19	21	CD	structure_element	In addition to the CD and KBD, MKP7 has a long C-terminal region that contains both nuclear localization and export sequences by which MKP7 shuttles between the nucleus and the cytoplasm (Fig. 2a).	RESULTS
26	29	KBD	structure_element	In addition to the CD and KBD, MKP7 has a long C-terminal region that contains both nuclear localization and export sequences by which MKP7 shuttles between the nucleus and the cytoplasm (Fig. 2a).	RESULTS
31	35	MKP7	protein	In addition to the CD and KBD, MKP7 has a long C-terminal region that contains both nuclear localization and export sequences by which MKP7 shuttles between the nucleus and the cytoplasm (Fig. 2a).	RESULTS
47	64	C-terminal region	structure_element	In addition to the CD and KBD, MKP7 has a long C-terminal region that contains both nuclear localization and export sequences by which MKP7 shuttles between the nucleus and the cytoplasm (Fig. 2a).	RESULTS
135	139	MKP7	protein	In addition to the CD and KBD, MKP7 has a long C-terminal region that contains both nuclear localization and export sequences by which MKP7 shuttles between the nucleus and the cytoplasm (Fig. 2a).	RESULTS
49	66	N-terminal domain	structure_element	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
74	78	MKP7	protein	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
89	93	JNK1	protein	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
94	111	dephosphorylation	ptm	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
135	142	kinetic	evidence	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
172	182	truncation	experimental_method	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
186	190	MKP7	protein	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
192	201	MKP7ΔC304	mutant	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
212	217	5–303	residue_range	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
223	227	MKP7	protein	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
228	230	CD	structure_element	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
241	248	156–301	residue_range	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
258	272	phosphorylated	protein_state	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
273	277	JNK1	protein	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
279	280	p	protein_state	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
280	284	JNK1	protein	To quantitatively assess the contribution of the N-terminal domain to the MKP7-catalysed JNK1 dephosphorylation, we first measured the kinetic parameters of the C-terminal truncation of MKP7 (MKP7ΔC304, residues 5–303) and MKP7-CD (residues 156–301) towards phosphorylated JNK1 (pJNK1).	RESULTS
20	46	variation of initial rates	evidence	Figure 2b shows the variation of initial rates of the MKP7ΔC304 and MKP7-CD-catalysed reaction with the concentration of phospho-JNK1. Because the concentrations of MKP7 and pJNK1 were comparable in the reaction, the assumption that the free-substrate concentration is equal to the total substrate concentration is not valid.	RESULTS
54	63	MKP7ΔC304	mutant	Figure 2b shows the variation of initial rates of the MKP7ΔC304 and MKP7-CD-catalysed reaction with the concentration of phospho-JNK1. Because the concentrations of MKP7 and pJNK1 were comparable in the reaction, the assumption that the free-substrate concentration is equal to the total substrate concentration is not valid.	RESULTS
68	72	MKP7	protein	Figure 2b shows the variation of initial rates of the MKP7ΔC304 and MKP7-CD-catalysed reaction with the concentration of phospho-JNK1. Because the concentrations of MKP7 and pJNK1 were comparable in the reaction, the assumption that the free-substrate concentration is equal to the total substrate concentration is not valid.	RESULTS
73	75	CD	structure_element	Figure 2b shows the variation of initial rates of the MKP7ΔC304 and MKP7-CD-catalysed reaction with the concentration of phospho-JNK1. Because the concentrations of MKP7 and pJNK1 were comparable in the reaction, the assumption that the free-substrate concentration is equal to the total substrate concentration is not valid.	RESULTS
121	128	phospho	protein_state	Figure 2b shows the variation of initial rates of the MKP7ΔC304 and MKP7-CD-catalysed reaction with the concentration of phospho-JNK1. Because the concentrations of MKP7 and pJNK1 were comparable in the reaction, the assumption that the free-substrate concentration is equal to the total substrate concentration is not valid.	RESULTS
129	133	JNK1	protein	Figure 2b shows the variation of initial rates of the MKP7ΔC304 and MKP7-CD-catalysed reaction with the concentration of phospho-JNK1. Because the concentrations of MKP7 and pJNK1 were comparable in the reaction, the assumption that the free-substrate concentration is equal to the total substrate concentration is not valid.	RESULTS
165	169	MKP7	protein	Figure 2b shows the variation of initial rates of the MKP7ΔC304 and MKP7-CD-catalysed reaction with the concentration of phospho-JNK1. Because the concentrations of MKP7 and pJNK1 were comparable in the reaction, the assumption that the free-substrate concentration is equal to the total substrate concentration is not valid.	RESULTS
174	175	p	protein_state	Figure 2b shows the variation of initial rates of the MKP7ΔC304 and MKP7-CD-catalysed reaction with the concentration of phospho-JNK1. Because the concentrations of MKP7 and pJNK1 were comparable in the reaction, the assumption that the free-substrate concentration is equal to the total substrate concentration is not valid.	RESULTS
175	179	JNK1	protein	Figure 2b shows the variation of initial rates of the MKP7ΔC304 and MKP7-CD-catalysed reaction with the concentration of phospho-JNK1. Because the concentrations of MKP7 and pJNK1 were comparable in the reaction, the assumption that the free-substrate concentration is equal to the total substrate concentration is not valid.	RESULTS
10	22	kinetic data	evidence	Thus, the kinetic data were analysed using the general initial velocity equation, taking substrate depletion into account:	RESULTS
55	80	initial velocity equation	evidence	Thus, the kinetic data were analysed using the general initial velocity equation, taking substrate depletion into account:	RESULTS
4	8	kcat	evidence	The kcat and Km of the MKP7-CD (0.028 s−1 and 0.26 μM) so determined were nearly identical to those of MKP7ΔC304 (0.029 s−1 and 0.27 μM), indicating that the MKP7-KBD has no effect on enzyme catalysis.	RESULTS
13	15	Km	evidence	The kcat and Km of the MKP7-CD (0.028 s−1 and 0.26 μM) so determined were nearly identical to those of MKP7ΔC304 (0.029 s−1 and 0.27 μM), indicating that the MKP7-KBD has no effect on enzyme catalysis.	RESULTS
23	27	MKP7	protein	The kcat and Km of the MKP7-CD (0.028 s−1 and 0.26 μM) so determined were nearly identical to those of MKP7ΔC304 (0.029 s−1 and 0.27 μM), indicating that the MKP7-KBD has no effect on enzyme catalysis.	RESULTS
28	30	CD	structure_element	The kcat and Km of the MKP7-CD (0.028 s−1 and 0.26 μM) so determined were nearly identical to those of MKP7ΔC304 (0.029 s−1 and 0.27 μM), indicating that the MKP7-KBD has no effect on enzyme catalysis.	RESULTS
103	112	MKP7ΔC304	mutant	The kcat and Km of the MKP7-CD (0.028 s−1 and 0.26 μM) so determined were nearly identical to those of MKP7ΔC304 (0.029 s−1 and 0.27 μM), indicating that the MKP7-KBD has no effect on enzyme catalysis.	RESULTS
158	162	MKP7	protein	The kcat and Km of the MKP7-CD (0.028 s−1 and 0.26 μM) so determined were nearly identical to those of MKP7ΔC304 (0.029 s−1 and 0.27 μM), indicating that the MKP7-KBD has no effect on enzyme catalysis.	RESULTS
163	166	KBD	structure_element	The kcat and Km of the MKP7-CD (0.028 s−1 and 0.26 μM) so determined were nearly identical to those of MKP7ΔC304 (0.029 s−1 and 0.27 μM), indicating that the MKP7-KBD has no effect on enzyme catalysis.	RESULTS
36	40	JNK1	protein	We next examined the interaction of JNK1 with the CD and KBD of MKP7 by gel filtration analysis.	RESULTS
50	52	CD	structure_element	We next examined the interaction of JNK1 with the CD and KBD of MKP7 by gel filtration analysis.	RESULTS
57	60	KBD	structure_element	We next examined the interaction of JNK1 with the CD and KBD of MKP7 by gel filtration analysis.	RESULTS
64	68	MKP7	protein	We next examined the interaction of JNK1 with the CD and KBD of MKP7 by gel filtration analysis.	RESULTS
72	95	gel filtration analysis	experimental_method	We next examined the interaction of JNK1 with the CD and KBD of MKP7 by gel filtration analysis.	RESULTS
28	30	CD	structure_element	When 3 molar equivalents of CD were mixed with 1 molar equivalent of JNK1, a significant amount of CD co-migrated with JNK1 to earlier fractions, and the excess amount of CD was eluted from the size exclusion column as a monomer, indicating stable complex formation (Fig. 2c).	RESULTS
69	73	JNK1	protein	When 3 molar equivalents of CD were mixed with 1 molar equivalent of JNK1, a significant amount of CD co-migrated with JNK1 to earlier fractions, and the excess amount of CD was eluted from the size exclusion column as a monomer, indicating stable complex formation (Fig. 2c).	RESULTS
99	101	CD	structure_element	When 3 molar equivalents of CD were mixed with 1 molar equivalent of JNK1, a significant amount of CD co-migrated with JNK1 to earlier fractions, and the excess amount of CD was eluted from the size exclusion column as a monomer, indicating stable complex formation (Fig. 2c).	RESULTS
119	123	JNK1	protein	When 3 molar equivalents of CD were mixed with 1 molar equivalent of JNK1, a significant amount of CD co-migrated with JNK1 to earlier fractions, and the excess amount of CD was eluted from the size exclusion column as a monomer, indicating stable complex formation (Fig. 2c).	RESULTS
171	173	CD	structure_element	When 3 molar equivalents of CD were mixed with 1 molar equivalent of JNK1, a significant amount of CD co-migrated with JNK1 to earlier fractions, and the excess amount of CD was eluted from the size exclusion column as a monomer, indicating stable complex formation (Fig. 2c).	RESULTS
221	228	monomer	oligomeric_state	When 3 molar equivalents of CD were mixed with 1 molar equivalent of JNK1, a significant amount of CD co-migrated with JNK1 to earlier fractions, and the excess amount of CD was eluted from the size exclusion column as a monomer, indicating stable complex formation (Fig. 2c).	RESULTS
16	24	KBD–JNK1	complex_assembly	In contrast, no KBD–JNK1 complex was detected when 3 molar equivalents of KBD were mixed with 1 molar equivalent of JNK1.	RESULTS
74	77	KBD	structure_element	In contrast, no KBD–JNK1 complex was detected when 3 molar equivalents of KBD were mixed with 1 molar equivalent of JNK1.	RESULTS
116	120	JNK1	protein	In contrast, no KBD–JNK1 complex was detected when 3 molar equivalents of KBD were mixed with 1 molar equivalent of JNK1.	RESULTS
23	35	JNK1–MKP7-CD	complex_assembly	To further confirm the JNK1–MKP7-CD interaction, we performed a pull-down assay using the purified proteins.	RESULTS
64	79	pull-down assay	experimental_method	To further confirm the JNK1–MKP7-CD interaction, we performed a pull-down assay using the purified proteins.	RESULTS
25	27	CD	structure_element	As shown in Fig. 2d, the CD of MKP7 can be pulled down by JNK1, while the KBD failed to bind to the counterpart protein.	RESULTS
31	35	MKP7	protein	As shown in Fig. 2d, the CD of MKP7 can be pulled down by JNK1, while the KBD failed to bind to the counterpart protein.	RESULTS
58	62	JNK1	protein	As shown in Fig. 2d, the CD of MKP7 can be pulled down by JNK1, while the KBD failed to bind to the counterpart protein.	RESULTS
74	77	KBD	structure_element	As shown in Fig. 2d, the CD of MKP7 can be pulled down by JNK1, while the KBD failed to bind to the counterpart protein.	RESULTS
43	45	CD	structure_element	Taken together, our data indicate that the CD of MKP7, but not the KBD domain, is responsible for JNK substrate-binding and enzymatic specificity.	RESULTS
49	53	MKP7	protein	Taken together, our data indicate that the CD of MKP7, but not the KBD domain, is responsible for JNK substrate-binding and enzymatic specificity.	RESULTS
67	70	KBD	structure_element	Taken together, our data indicate that the CD of MKP7, but not the KBD domain, is responsible for JNK substrate-binding and enzymatic specificity.	RESULTS
98	101	JNK	protein_type	Taken together, our data indicate that the CD of MKP7, but not the KBD domain, is responsible for JNK substrate-binding and enzymatic specificity.	RESULTS
0	17	Crystal structure	evidence	Crystal structure of JNK1 in complex with the MKP7-CD	RESULTS
21	25	JNK1	protein	Crystal structure of JNK1 in complex with the MKP7-CD	RESULTS
26	41	in complex with	protein_state	Crystal structure of JNK1 in complex with the MKP7-CD	RESULTS
46	50	MKP7	protein	Crystal structure of JNK1 in complex with the MKP7-CD	RESULTS
51	53	CD	structure_element	Crystal structure of JNK1 in complex with the MKP7-CD	RESULTS
37	41	JNK1	protein	To understand the molecular basis of JNK1 recognition by MKP7, we determined the crystal structure of unphosphorylated JNK1 in complex with the MKP7-CD (Fig. 3a, Supplementary Fig. 1a and Table 1).	RESULTS
57	61	MKP7	protein	To understand the molecular basis of JNK1 recognition by MKP7, we determined the crystal structure of unphosphorylated JNK1 in complex with the MKP7-CD (Fig. 3a, Supplementary Fig. 1a and Table 1).	RESULTS
81	98	crystal structure	evidence	To understand the molecular basis of JNK1 recognition by MKP7, we determined the crystal structure of unphosphorylated JNK1 in complex with the MKP7-CD (Fig. 3a, Supplementary Fig. 1a and Table 1).	RESULTS
102	118	unphosphorylated	protein_state	To understand the molecular basis of JNK1 recognition by MKP7, we determined the crystal structure of unphosphorylated JNK1 in complex with the MKP7-CD (Fig. 3a, Supplementary Fig. 1a and Table 1).	RESULTS
119	123	JNK1	protein	To understand the molecular basis of JNK1 recognition by MKP7, we determined the crystal structure of unphosphorylated JNK1 in complex with the MKP7-CD (Fig. 3a, Supplementary Fig. 1a and Table 1).	RESULTS
124	139	in complex with	protein_state	To understand the molecular basis of JNK1 recognition by MKP7, we determined the crystal structure of unphosphorylated JNK1 in complex with the MKP7-CD (Fig. 3a, Supplementary Fig. 1a and Table 1).	RESULTS
144	148	MKP7	protein	To understand the molecular basis of JNK1 recognition by MKP7, we determined the crystal structure of unphosphorylated JNK1 in complex with the MKP7-CD (Fig. 3a, Supplementary Fig. 1a and Table 1).	RESULTS
149	151	CD	structure_element	To understand the molecular basis of JNK1 recognition by MKP7, we determined the crystal structure of unphosphorylated JNK1 in complex with the MKP7-CD (Fig. 3a, Supplementary Fig. 1a and Table 1).	RESULTS
16	20	JNK1	protein	In the complex, JNK1 has its characteristic bilobal structure comprising an N-terminal lobe rich in β-sheet and a C-terminal lobe that is mostly α-helical.	RESULTS
76	91	N-terminal lobe	structure_element	In the complex, JNK1 has its characteristic bilobal structure comprising an N-terminal lobe rich in β-sheet and a C-terminal lobe that is mostly α-helical.	RESULTS
100	107	β-sheet	structure_element	In the complex, JNK1 has its characteristic bilobal structure comprising an N-terminal lobe rich in β-sheet and a C-terminal lobe that is mostly α-helical.	RESULTS
114	129	C-terminal lobe	structure_element	In the complex, JNK1 has its characteristic bilobal structure comprising an N-terminal lobe rich in β-sheet and a C-terminal lobe that is mostly α-helical.	RESULTS
145	154	α-helical	structure_element	In the complex, JNK1 has its characteristic bilobal structure comprising an N-terminal lobe rich in β-sheet and a C-terminal lobe that is mostly α-helical.	RESULTS
23	27	MKP7	protein	The overall folding of MKP7-CD is typical of DUSPs, with a central twisted five-stranded β-sheet surrounded by six α-helices.	RESULTS
28	30	CD	structure_element	The overall folding of MKP7-CD is typical of DUSPs, with a central twisted five-stranded β-sheet surrounded by six α-helices.	RESULTS
45	50	DUSPs	protein_type	The overall folding of MKP7-CD is typical of DUSPs, with a central twisted five-stranded β-sheet surrounded by six α-helices.	RESULTS
67	96	twisted five-stranded β-sheet	structure_element	The overall folding of MKP7-CD is typical of DUSPs, with a central twisted five-stranded β-sheet surrounded by six α-helices.	RESULTS
115	124	α-helices	structure_element	The overall folding of MKP7-CD is typical of DUSPs, with a central twisted five-stranded β-sheet surrounded by six α-helices.	RESULTS
16	23	β-sheet	structure_element	One side of the β-sheet is covered with two α-helices and the other is covered with four α-helices (Fig. 3b).	RESULTS
44	53	α-helices	structure_element	One side of the β-sheet is covered with two α-helices and the other is covered with four α-helices (Fig. 3b).	RESULTS
89	98	α-helices	structure_element	One side of the β-sheet is covered with two α-helices and the other is covered with four α-helices (Fig. 3b).	RESULTS
4	20	catalytic domain	structure_element	The catalytic domain of MKP7 interacts with JNK1 through a contiguous surface area that is remote from the active site.	RESULTS
24	28	MKP7	protein	The catalytic domain of MKP7 interacts with JNK1 through a contiguous surface area that is remote from the active site.	RESULTS
44	48	JNK1	protein	The catalytic domain of MKP7 interacts with JNK1 through a contiguous surface area that is remote from the active site.	RESULTS
107	118	active site	site	The catalytic domain of MKP7 interacts with JNK1 through a contiguous surface area that is remote from the active site.	RESULTS
0	4	MKP7	protein	MKP7-CD is positioned onto the JNK1 molecule so that the active site of the phosphatase faces towards the activation segment.	RESULTS
5	7	CD	structure_element	MKP7-CD is positioned onto the JNK1 molecule so that the active site of the phosphatase faces towards the activation segment.	RESULTS
31	35	JNK1	protein	MKP7-CD is positioned onto the JNK1 molecule so that the active site of the phosphatase faces towards the activation segment.	RESULTS
57	68	active site	site	MKP7-CD is positioned onto the JNK1 molecule so that the active site of the phosphatase faces towards the activation segment.	RESULTS
76	87	phosphatase	protein_type	MKP7-CD is positioned onto the JNK1 molecule so that the active site of the phosphatase faces towards the activation segment.	RESULTS
106	124	activation segment	structure_element	MKP7-CD is positioned onto the JNK1 molecule so that the active site of the phosphatase faces towards the activation segment.	RESULTS
6	15	alignment	experimental_method	In an alignment of the structure of MKP7-CD with that of VHR, an atypical ‘MKP' consisting of only a catalytic domain, 119 of 147 MKP7-CD residues could be superimposed with a r.m.s.d. (root mean squared deviation) of 1.05 Å (Fig. 3c).	RESULTS
23	32	structure	evidence	In an alignment of the structure of MKP7-CD with that of VHR, an atypical ‘MKP' consisting of only a catalytic domain, 119 of 147 MKP7-CD residues could be superimposed with a r.m.s.d. (root mean squared deviation) of 1.05 Å (Fig. 3c).	RESULTS
36	40	MKP7	protein	In an alignment of the structure of MKP7-CD with that of VHR, an atypical ‘MKP' consisting of only a catalytic domain, 119 of 147 MKP7-CD residues could be superimposed with a r.m.s.d. (root mean squared deviation) of 1.05 Å (Fig. 3c).	RESULTS
41	43	CD	structure_element	In an alignment of the structure of MKP7-CD with that of VHR, an atypical ‘MKP' consisting of only a catalytic domain, 119 of 147 MKP7-CD residues could be superimposed with a r.m.s.d. (root mean squared deviation) of 1.05 Å (Fig. 3c).	RESULTS
57	60	VHR	protein	In an alignment of the structure of MKP7-CD with that of VHR, an atypical ‘MKP' consisting of only a catalytic domain, 119 of 147 MKP7-CD residues could be superimposed with a r.m.s.d. (root mean squared deviation) of 1.05 Å (Fig. 3c).	RESULTS
75	78	MKP	protein_type	In an alignment of the structure of MKP7-CD with that of VHR, an atypical ‘MKP' consisting of only a catalytic domain, 119 of 147 MKP7-CD residues could be superimposed with a r.m.s.d. (root mean squared deviation) of 1.05 Å (Fig. 3c).	RESULTS
101	117	catalytic domain	structure_element	In an alignment of the structure of MKP7-CD with that of VHR, an atypical ‘MKP' consisting of only a catalytic domain, 119 of 147 MKP7-CD residues could be superimposed with a r.m.s.d. (root mean squared deviation) of 1.05 Å (Fig. 3c).	RESULTS
130	134	MKP7	protein	In an alignment of the structure of MKP7-CD with that of VHR, an atypical ‘MKP' consisting of only a catalytic domain, 119 of 147 MKP7-CD residues could be superimposed with a r.m.s.d. (root mean squared deviation) of 1.05 Å (Fig. 3c).	RESULTS
135	137	CD	structure_element	In an alignment of the structure of MKP7-CD with that of VHR, an atypical ‘MKP' consisting of only a catalytic domain, 119 of 147 MKP7-CD residues could be superimposed with a r.m.s.d. (root mean squared deviation) of 1.05 Å (Fig. 3c).	RESULTS
156	168	superimposed	experimental_method	In an alignment of the structure of MKP7-CD with that of VHR, an atypical ‘MKP' consisting of only a catalytic domain, 119 of 147 MKP7-CD residues could be superimposed with a r.m.s.d. (root mean squared deviation) of 1.05 Å (Fig. 3c).	RESULTS
176	184	r.m.s.d.	evidence	In an alignment of the structure of MKP7-CD with that of VHR, an atypical ‘MKP' consisting of only a catalytic domain, 119 of 147 MKP7-CD residues could be superimposed with a r.m.s.d. (root mean squared deviation) of 1.05 Å (Fig. 3c).	RESULTS
186	213	root mean squared deviation	evidence	In an alignment of the structure of MKP7-CD with that of VHR, an atypical ‘MKP' consisting of only a catalytic domain, 119 of 147 MKP7-CD residues could be superimposed with a r.m.s.d. (root mean squared deviation) of 1.05 Å (Fig. 3c).	RESULTS
37	42	helix	structure_element	The most striking difference is that helix α0 and loop α0–β1 of VHR are absent in MKP7-CD.	RESULTS
43	45	α0	structure_element	The most striking difference is that helix α0 and loop α0–β1 of VHR are absent in MKP7-CD.	RESULTS
50	54	loop	structure_element	The most striking difference is that helix α0 and loop α0–β1 of VHR are absent in MKP7-CD.	RESULTS
55	60	α0–β1	structure_element	The most striking difference is that helix α0 and loop α0–β1 of VHR are absent in MKP7-CD.	RESULTS
64	67	VHR	protein	The most striking difference is that helix α0 and loop α0–β1 of VHR are absent in MKP7-CD.	RESULTS
82	86	MKP7	protein	The most striking difference is that helix α0 and loop α0–β1 of VHR are absent in MKP7-CD.	RESULTS
87	89	CD	structure_element	The most striking difference is that helix α0 and loop α0–β1 of VHR are absent in MKP7-CD.	RESULTS
43	46	VHR	protein	Another region that cannot be aligned with VHR is found in loop β3–β4.	RESULTS
59	63	loop	structure_element	Another region that cannot be aligned with VHR is found in loop β3–β4.	RESULTS
64	69	β3–β4	structure_element	Another region that cannot be aligned with VHR is found in loop β3–β4.	RESULTS
5	9	loop	structure_element	This loop is shortened by nine residues in MKP7-CD compared with that in VHR.	RESULTS
43	47	MKP7	protein	This loop is shortened by nine residues in MKP7-CD compared with that in VHR.	RESULTS
48	50	CD	structure_element	This loop is shortened by nine residues in MKP7-CD compared with that in VHR.	RESULTS
73	76	VHR	protein	This loop is shortened by nine residues in MKP7-CD compared with that in VHR.	RESULTS
6	11	helix	structure_element	Since helix α0 and the following loop α0–β1 are known for a substrate-recognition motif of VHR and other phosphatases, the absence of these moieties implicates a different substrate-binding mode of MKP7.	RESULTS
12	14	α0	structure_element	Since helix α0 and the following loop α0–β1 are known for a substrate-recognition motif of VHR and other phosphatases, the absence of these moieties implicates a different substrate-binding mode of MKP7.	RESULTS
33	37	loop	structure_element	Since helix α0 and the following loop α0–β1 are known for a substrate-recognition motif of VHR and other phosphatases, the absence of these moieties implicates a different substrate-binding mode of MKP7.	RESULTS
38	43	α0–β1	structure_element	Since helix α0 and the following loop α0–β1 are known for a substrate-recognition motif of VHR and other phosphatases, the absence of these moieties implicates a different substrate-binding mode of MKP7.	RESULTS
60	87	substrate-recognition motif	site	Since helix α0 and the following loop α0–β1 are known for a substrate-recognition motif of VHR and other phosphatases, the absence of these moieties implicates a different substrate-binding mode of MKP7.	RESULTS
91	94	VHR	protein	Since helix α0 and the following loop α0–β1 are known for a substrate-recognition motif of VHR and other phosphatases, the absence of these moieties implicates a different substrate-binding mode of MKP7.	RESULTS
105	117	phosphatases	protein_type	Since helix α0 and the following loop α0–β1 are known for a substrate-recognition motif of VHR and other phosphatases, the absence of these moieties implicates a different substrate-binding mode of MKP7.	RESULTS
198	202	MKP7	protein	Since helix α0 and the following loop α0–β1 are known for a substrate-recognition motif of VHR and other phosphatases, the absence of these moieties implicates a different substrate-binding mode of MKP7.	RESULTS
4	15	active site	site	The active site of MKP7 consists of the phosphate-binding loop (P-loop, Cys244-Leu245-Ala246-Gly247-Ile248-Ser249-Arg250), and Asp213 in the general acid loop (Fig. 3b and Supplementary Fig. 1b).	RESULTS
19	23	MKP7	protein	The active site of MKP7 consists of the phosphate-binding loop (P-loop, Cys244-Leu245-Ala246-Gly247-Ile248-Ser249-Arg250), and Asp213 in the general acid loop (Fig. 3b and Supplementary Fig. 1b).	RESULTS
40	62	phosphate-binding loop	structure_element	The active site of MKP7 consists of the phosphate-binding loop (P-loop, Cys244-Leu245-Ala246-Gly247-Ile248-Ser249-Arg250), and Asp213 in the general acid loop (Fig. 3b and Supplementary Fig. 1b).	RESULTS
64	70	P-loop	structure_element	The active site of MKP7 consists of the phosphate-binding loop (P-loop, Cys244-Leu245-Ala246-Gly247-Ile248-Ser249-Arg250), and Asp213 in the general acid loop (Fig. 3b and Supplementary Fig. 1b).	RESULTS
72	78	Cys244	residue_name_number	The active site of MKP7 consists of the phosphate-binding loop (P-loop, Cys244-Leu245-Ala246-Gly247-Ile248-Ser249-Arg250), and Asp213 in the general acid loop (Fig. 3b and Supplementary Fig. 1b).	RESULTS
79	85	Leu245	residue_name_number	The active site of MKP7 consists of the phosphate-binding loop (P-loop, Cys244-Leu245-Ala246-Gly247-Ile248-Ser249-Arg250), and Asp213 in the general acid loop (Fig. 3b and Supplementary Fig. 1b).	RESULTS
86	92	Ala246	residue_name_number	The active site of MKP7 consists of the phosphate-binding loop (P-loop, Cys244-Leu245-Ala246-Gly247-Ile248-Ser249-Arg250), and Asp213 in the general acid loop (Fig. 3b and Supplementary Fig. 1b).	RESULTS
93	99	Gly247	residue_name_number	The active site of MKP7 consists of the phosphate-binding loop (P-loop, Cys244-Leu245-Ala246-Gly247-Ile248-Ser249-Arg250), and Asp213 in the general acid loop (Fig. 3b and Supplementary Fig. 1b).	RESULTS
100	106	Ile248	residue_name_number	The active site of MKP7 consists of the phosphate-binding loop (P-loop, Cys244-Leu245-Ala246-Gly247-Ile248-Ser249-Arg250), and Asp213 in the general acid loop (Fig. 3b and Supplementary Fig. 1b).	RESULTS
107	113	Ser249	residue_name_number	The active site of MKP7 consists of the phosphate-binding loop (P-loop, Cys244-Leu245-Ala246-Gly247-Ile248-Ser249-Arg250), and Asp213 in the general acid loop (Fig. 3b and Supplementary Fig. 1b).	RESULTS
114	120	Arg250	residue_name_number	The active site of MKP7 consists of the phosphate-binding loop (P-loop, Cys244-Leu245-Ala246-Gly247-Ile248-Ser249-Arg250), and Asp213 in the general acid loop (Fig. 3b and Supplementary Fig. 1b).	RESULTS
127	133	Asp213	residue_name_number	The active site of MKP7 consists of the phosphate-binding loop (P-loop, Cys244-Leu245-Ala246-Gly247-Ile248-Ser249-Arg250), and Asp213 in the general acid loop (Fig. 3b and Supplementary Fig. 1b).	RESULTS
141	158	general acid loop	structure_element	The active site of MKP7 consists of the phosphate-binding loop (P-loop, Cys244-Leu245-Ala246-Gly247-Ile248-Ser249-Arg250), and Asp213 in the general acid loop (Fig. 3b and Supplementary Fig. 1b).	RESULTS
4	8	MKP7	protein	The MKP7-CD structure near the active site exhibits a typical active conformation as found in VHR and other PTPs.	RESULTS
9	11	CD	structure_element	The MKP7-CD structure near the active site exhibits a typical active conformation as found in VHR and other PTPs.	RESULTS
12	21	structure	evidence	The MKP7-CD structure near the active site exhibits a typical active conformation as found in VHR and other PTPs.	RESULTS
31	42	active site	site	The MKP7-CD structure near the active site exhibits a typical active conformation as found in VHR and other PTPs.	RESULTS
62	81	active conformation	protein_state	The MKP7-CD structure near the active site exhibits a typical active conformation as found in VHR and other PTPs.	RESULTS
94	97	VHR	protein	The MKP7-CD structure near the active site exhibits a typical active conformation as found in VHR and other PTPs.	RESULTS
108	112	PTPs	protein_type	The MKP7-CD structure near the active site exhibits a typical active conformation as found in VHR and other PTPs.	RESULTS
4	21	catalytic residue	site	The catalytic residue, Cys244, is located just after strand β5 and optimally positioned for nucleophilic attack.	RESULTS
23	29	Cys244	residue_name_number	The catalytic residue, Cys244, is located just after strand β5 and optimally positioned for nucleophilic attack.	RESULTS
53	59	strand	structure_element	The catalytic residue, Cys244, is located just after strand β5 and optimally positioned for nucleophilic attack.	RESULTS
60	62	β5	structure_element	The catalytic residue, Cys244, is located just after strand β5 and optimally positioned for nucleophilic attack.	RESULTS
0	6	Asp213	residue_name_number	Asp213 in MKP7 also adopts a position similar to that of Asp92 in VHR (Supplementary Fig. 1c), indicating that Asp213 is likely to function as the general acid in MKP7.	RESULTS
10	14	MKP7	protein	Asp213 in MKP7 also adopts a position similar to that of Asp92 in VHR (Supplementary Fig. 1c), indicating that Asp213 is likely to function as the general acid in MKP7.	RESULTS
57	62	Asp92	residue_name_number	Asp213 in MKP7 also adopts a position similar to that of Asp92 in VHR (Supplementary Fig. 1c), indicating that Asp213 is likely to function as the general acid in MKP7.	RESULTS
66	69	VHR	protein	Asp213 in MKP7 also adopts a position similar to that of Asp92 in VHR (Supplementary Fig. 1c), indicating that Asp213 is likely to function as the general acid in MKP7.	RESULTS
111	117	Asp213	residue_name_number	Asp213 in MKP7 also adopts a position similar to that of Asp92 in VHR (Supplementary Fig. 1c), indicating that Asp213 is likely to function as the general acid in MKP7.	RESULTS
163	167	MKP7	protein	Asp213 in MKP7 also adopts a position similar to that of Asp92 in VHR (Supplementary Fig. 1c), indicating that Asp213 is likely to function as the general acid in MKP7.	RESULTS
34	42	chloride	chemical	We also observed the binding of a chloride ion in the active site of MKP7-CD.	RESULTS
54	65	active site	site	We also observed the binding of a chloride ion in the active site of MKP7-CD.	RESULTS
69	73	MKP7	protein	We also observed the binding of a chloride ion in the active site of MKP7-CD.	RESULTS
74	76	CD	structure_element	We also observed the binding of a chloride ion in the active site of MKP7-CD.	RESULTS
30	36	Cys244	residue_name_number	It is located 3.36 Å from the Cys244 side chain and makes electrostatic interactions with the dipole moment of helix α3 and with several main-chain amide groups.	RESULTS
58	84	electrostatic interactions	bond_interaction	It is located 3.36 Å from the Cys244 side chain and makes electrostatic interactions with the dipole moment of helix α3 and with several main-chain amide groups.	RESULTS
111	116	helix	structure_element	It is located 3.36 Å from the Cys244 side chain and makes electrostatic interactions with the dipole moment of helix α3 and with several main-chain amide groups.	RESULTS
117	119	α3	structure_element	It is located 3.36 Å from the Cys244 side chain and makes electrostatic interactions with the dipole moment of helix α3 and with several main-chain amide groups.	RESULTS
18	36	strictly conserved	protein_state	The side chain of strictly conserved Arg250 is oriented towards the negatively charged chloride, similar to the canonical phosphate-coordinating conformation.	RESULTS
37	43	Arg250	residue_name_number	The side chain of strictly conserved Arg250 is oriented towards the negatively charged chloride, similar to the canonical phosphate-coordinating conformation.	RESULTS
87	95	chloride	chemical	The side chain of strictly conserved Arg250 is oriented towards the negatively charged chloride, similar to the canonical phosphate-coordinating conformation.	RESULTS
122	157	phosphate-coordinating conformation	structure_element	The side chain of strictly conserved Arg250 is oriented towards the negatively charged chloride, similar to the canonical phosphate-coordinating conformation.	RESULTS
10	18	chloride	chemical	Thus this chloride ion is a mimic for the phosphate group of the substrate, as revealed by a comparison with the structure of PTP1B in complex with phosphotyrosine (Supplementary Fig. 1d).	RESULTS
42	51	phosphate	chemical	Thus this chloride ion is a mimic for the phosphate group of the substrate, as revealed by a comparison with the structure of PTP1B in complex with phosphotyrosine (Supplementary Fig. 1d).	RESULTS
113	122	structure	evidence	Thus this chloride ion is a mimic for the phosphate group of the substrate, as revealed by a comparison with the structure of PTP1B in complex with phosphotyrosine (Supplementary Fig. 1d).	RESULTS
126	131	PTP1B	protein	Thus this chloride ion is a mimic for the phosphate group of the substrate, as revealed by a comparison with the structure of PTP1B in complex with phosphotyrosine (Supplementary Fig. 1d).	RESULTS
132	147	in complex with	protein_state	Thus this chloride ion is a mimic for the phosphate group of the substrate, as revealed by a comparison with the structure of PTP1B in complex with phosphotyrosine (Supplementary Fig. 1d).	RESULTS
148	163	phosphotyrosine	residue_name	Thus this chloride ion is a mimic for the phosphate group of the substrate, as revealed by a comparison with the structure of PTP1B in complex with phosphotyrosine (Supplementary Fig. 1d).	RESULTS
49	53	MKP7	protein	Although the catalytically important residues in MKP7-CD are well aligned with those in VHR, the residues in the P-loop of MKP7 are smaller and have a more hydrophobic character than those of VHR (Cys124-Arg125-Glu126-Gly127-Tyr128-Gly129-Arg130; Fig. 3b,c).	RESULTS
54	56	CD	structure_element	Although the catalytically important residues in MKP7-CD are well aligned with those in VHR, the residues in the P-loop of MKP7 are smaller and have a more hydrophobic character than those of VHR (Cys124-Arg125-Glu126-Gly127-Tyr128-Gly129-Arg130; Fig. 3b,c).	RESULTS
88	91	VHR	protein	Although the catalytically important residues in MKP7-CD are well aligned with those in VHR, the residues in the P-loop of MKP7 are smaller and have a more hydrophobic character than those of VHR (Cys124-Arg125-Glu126-Gly127-Tyr128-Gly129-Arg130; Fig. 3b,c).	RESULTS
113	119	P-loop	structure_element	Although the catalytically important residues in MKP7-CD are well aligned with those in VHR, the residues in the P-loop of MKP7 are smaller and have a more hydrophobic character than those of VHR (Cys124-Arg125-Glu126-Gly127-Tyr128-Gly129-Arg130; Fig. 3b,c).	RESULTS
123	127	MKP7	protein	Although the catalytically important residues in MKP7-CD are well aligned with those in VHR, the residues in the P-loop of MKP7 are smaller and have a more hydrophobic character than those of VHR (Cys124-Arg125-Glu126-Gly127-Tyr128-Gly129-Arg130; Fig. 3b,c).	RESULTS
192	195	VHR	protein	Although the catalytically important residues in MKP7-CD are well aligned with those in VHR, the residues in the P-loop of MKP7 are smaller and have a more hydrophobic character than those of VHR (Cys124-Arg125-Glu126-Gly127-Tyr128-Gly129-Arg130; Fig. 3b,c).	RESULTS
197	203	Cys124	residue_name_number	Although the catalytically important residues in MKP7-CD are well aligned with those in VHR, the residues in the P-loop of MKP7 are smaller and have a more hydrophobic character than those of VHR (Cys124-Arg125-Glu126-Gly127-Tyr128-Gly129-Arg130; Fig. 3b,c).	RESULTS
204	210	Arg125	residue_name_number	Although the catalytically important residues in MKP7-CD are well aligned with those in VHR, the residues in the P-loop of MKP7 are smaller and have a more hydrophobic character than those of VHR (Cys124-Arg125-Glu126-Gly127-Tyr128-Gly129-Arg130; Fig. 3b,c).	RESULTS
211	217	Glu126	residue_name_number	Although the catalytically important residues in MKP7-CD are well aligned with those in VHR, the residues in the P-loop of MKP7 are smaller and have a more hydrophobic character than those of VHR (Cys124-Arg125-Glu126-Gly127-Tyr128-Gly129-Arg130; Fig. 3b,c).	RESULTS
218	224	Gly127	residue_name_number	Although the catalytically important residues in MKP7-CD are well aligned with those in VHR, the residues in the P-loop of MKP7 are smaller and have a more hydrophobic character than those of VHR (Cys124-Arg125-Glu126-Gly127-Tyr128-Gly129-Arg130; Fig. 3b,c).	RESULTS
225	231	Tyr128	residue_name_number	Although the catalytically important residues in MKP7-CD are well aligned with those in VHR, the residues in the P-loop of MKP7 are smaller and have a more hydrophobic character than those of VHR (Cys124-Arg125-Glu126-Gly127-Tyr128-Gly129-Arg130; Fig. 3b,c).	RESULTS
232	238	Gly129	residue_name_number	Although the catalytically important residues in MKP7-CD are well aligned with those in VHR, the residues in the P-loop of MKP7 are smaller and have a more hydrophobic character than those of VHR (Cys124-Arg125-Glu126-Gly127-Tyr128-Gly129-Arg130; Fig. 3b,c).	RESULTS
239	245	Arg130	residue_name_number	Although the catalytically important residues in MKP7-CD are well aligned with those in VHR, the residues in the P-loop of MKP7 are smaller and have a more hydrophobic character than those of VHR (Cys124-Arg125-Glu126-Gly127-Tyr128-Gly129-Arg130; Fig. 3b,c).	RESULTS
162	174	phosphatases	protein_type	The difference in the polarity/hydrophobicity of the surface may also point to the origin of the differences in the substrate-recognition mechanism for these two phosphatases (Supplementary Fig. 1e,f).	RESULTS
16	20	MKP7	protein	In the complex, MKP7-CD and JNK1 form extensive protein–protein interactions involving the C-terminal helices of MKP7-CD and C-lobe of JNK1 (Fig. 3d,e).	RESULTS
21	23	CD	structure_element	In the complex, MKP7-CD and JNK1 form extensive protein–protein interactions involving the C-terminal helices of MKP7-CD and C-lobe of JNK1 (Fig. 3d,e).	RESULTS
28	32	JNK1	protein	In the complex, MKP7-CD and JNK1 form extensive protein–protein interactions involving the C-terminal helices of MKP7-CD and C-lobe of JNK1 (Fig. 3d,e).	RESULTS
91	109	C-terminal helices	structure_element	In the complex, MKP7-CD and JNK1 form extensive protein–protein interactions involving the C-terminal helices of MKP7-CD and C-lobe of JNK1 (Fig. 3d,e).	RESULTS
113	117	MKP7	protein	In the complex, MKP7-CD and JNK1 form extensive protein–protein interactions involving the C-terminal helices of MKP7-CD and C-lobe of JNK1 (Fig. 3d,e).	RESULTS
118	120	CD	structure_element	In the complex, MKP7-CD and JNK1 form extensive protein–protein interactions involving the C-terminal helices of MKP7-CD and C-lobe of JNK1 (Fig. 3d,e).	RESULTS
125	131	C-lobe	structure_element	In the complex, MKP7-CD and JNK1 form extensive protein–protein interactions involving the C-terminal helices of MKP7-CD and C-lobe of JNK1 (Fig. 3d,e).	RESULTS
135	139	JNK1	protein	In the complex, MKP7-CD and JNK1 form extensive protein–protein interactions involving the C-terminal helices of MKP7-CD and C-lobe of JNK1 (Fig. 3d,e).	RESULTS
76	93	C-terminal domain	structure_element	As a result, the buried solvent-accessible surface area is ∼1,315 Å. In the C-terminal domain, JNK1 has an insertion after the helix αG. This insertion consists of two helices (α1L14 and α2L14) that are common to all members of the MAPK family.	RESULTS
95	99	JNK1	protein	As a result, the buried solvent-accessible surface area is ∼1,315 Å. In the C-terminal domain, JNK1 has an insertion after the helix αG. This insertion consists of two helices (α1L14 and α2L14) that are common to all members of the MAPK family.	RESULTS
127	132	helix	structure_element	As a result, the buried solvent-accessible surface area is ∼1,315 Å. In the C-terminal domain, JNK1 has an insertion after the helix αG. This insertion consists of two helices (α1L14 and α2L14) that are common to all members of the MAPK family.	RESULTS
133	135	αG	structure_element	As a result, the buried solvent-accessible surface area is ∼1,315 Å. In the C-terminal domain, JNK1 has an insertion after the helix αG. This insertion consists of two helices (α1L14 and α2L14) that are common to all members of the MAPK family.	RESULTS
168	175	helices	structure_element	As a result, the buried solvent-accessible surface area is ∼1,315 Å. In the C-terminal domain, JNK1 has an insertion after the helix αG. This insertion consists of two helices (α1L14 and α2L14) that are common to all members of the MAPK family.	RESULTS
177	182	α1L14	structure_element	As a result, the buried solvent-accessible surface area is ∼1,315 Å. In the C-terminal domain, JNK1 has an insertion after the helix αG. This insertion consists of two helices (α1L14 and α2L14) that are common to all members of the MAPK family.	RESULTS
187	192	α2L14	structure_element	As a result, the buried solvent-accessible surface area is ∼1,315 Å. In the C-terminal domain, JNK1 has an insertion after the helix αG. This insertion consists of two helices (α1L14 and α2L14) that are common to all members of the MAPK family.	RESULTS
232	243	MAPK family	protein_type	As a result, the buried solvent-accessible surface area is ∼1,315 Å. In the C-terminal domain, JNK1 has an insertion after the helix αG. This insertion consists of two helices (α1L14 and α2L14) that are common to all members of the MAPK family.	RESULTS
4	23	interactive surface	site	The interactive surface in JNK1, formed by the helices αG and α2L14, displays a hydrophobic region, centred at Trp234 (Fig. 3d).	RESULTS
27	31	JNK1	protein	The interactive surface in JNK1, formed by the helices αG and α2L14, displays a hydrophobic region, centred at Trp234 (Fig. 3d).	RESULTS
47	54	helices	structure_element	The interactive surface in JNK1, formed by the helices αG and α2L14, displays a hydrophobic region, centred at Trp234 (Fig. 3d).	RESULTS
55	57	αG	structure_element	The interactive surface in JNK1, formed by the helices αG and α2L14, displays a hydrophobic region, centred at Trp234 (Fig. 3d).	RESULTS
62	67	α2L14	structure_element	The interactive surface in JNK1, formed by the helices αG and α2L14, displays a hydrophobic region, centred at Trp234 (Fig. 3d).	RESULTS
80	98	hydrophobic region	site	The interactive surface in JNK1, formed by the helices αG and α2L14, displays a hydrophobic region, centred at Trp234 (Fig. 3d).	RESULTS
111	117	Trp234	residue_name_number	The interactive surface in JNK1, formed by the helices αG and α2L14, displays a hydrophobic region, centred at Trp234 (Fig. 3d).	RESULTS
4	23	MKP7-docking region	site	The MKP7-docking region includes two helices, α4 and α5, and the general acid loop.	RESULTS
37	44	helices	structure_element	The MKP7-docking region includes two helices, α4 and α5, and the general acid loop.	RESULTS
46	48	α4	structure_element	The MKP7-docking region includes two helices, α4 and α5, and the general acid loop.	RESULTS
53	55	α5	structure_element	The MKP7-docking region includes two helices, α4 and α5, and the general acid loop.	RESULTS
65	82	general acid loop	structure_element	The MKP7-docking region includes two helices, α4 and α5, and the general acid loop.	RESULTS
21	27	Phe285	residue_name_number	The aromatic ring of Phe285 on MKP7 α5-helix is nestled in a hydrophobic pocket on JNK1, formed by side chains of Ile197, Leu198, Ile231, Trp234, Val256, Tyr259, Val260 and the aliphatic portion of His230 (Fig. 3d,f and Supplementary Fig. 1g).	RESULTS
31	35	MKP7	protein	The aromatic ring of Phe285 on MKP7 α5-helix is nestled in a hydrophobic pocket on JNK1, formed by side chains of Ile197, Leu198, Ile231, Trp234, Val256, Tyr259, Val260 and the aliphatic portion of His230 (Fig. 3d,f and Supplementary Fig. 1g).	RESULTS
36	44	α5-helix	structure_element	The aromatic ring of Phe285 on MKP7 α5-helix is nestled in a hydrophobic pocket on JNK1, formed by side chains of Ile197, Leu198, Ile231, Trp234, Val256, Tyr259, Val260 and the aliphatic portion of His230 (Fig. 3d,f and Supplementary Fig. 1g).	RESULTS
61	79	hydrophobic pocket	site	The aromatic ring of Phe285 on MKP7 α5-helix is nestled in a hydrophobic pocket on JNK1, formed by side chains of Ile197, Leu198, Ile231, Trp234, Val256, Tyr259, Val260 and the aliphatic portion of His230 (Fig. 3d,f and Supplementary Fig. 1g).	RESULTS
83	87	JNK1	protein	The aromatic ring of Phe285 on MKP7 α5-helix is nestled in a hydrophobic pocket on JNK1, formed by side chains of Ile197, Leu198, Ile231, Trp234, Val256, Tyr259, Val260 and the aliphatic portion of His230 (Fig. 3d,f and Supplementary Fig. 1g).	RESULTS
114	120	Ile197	residue_name_number	The aromatic ring of Phe285 on MKP7 α5-helix is nestled in a hydrophobic pocket on JNK1, formed by side chains of Ile197, Leu198, Ile231, Trp234, Val256, Tyr259, Val260 and the aliphatic portion of His230 (Fig. 3d,f and Supplementary Fig. 1g).	RESULTS
122	128	Leu198	residue_name_number	The aromatic ring of Phe285 on MKP7 α5-helix is nestled in a hydrophobic pocket on JNK1, formed by side chains of Ile197, Leu198, Ile231, Trp234, Val256, Tyr259, Val260 and the aliphatic portion of His230 (Fig. 3d,f and Supplementary Fig. 1g).	RESULTS
130	136	Ile231	residue_name_number	The aromatic ring of Phe285 on MKP7 α5-helix is nestled in a hydrophobic pocket on JNK1, formed by side chains of Ile197, Leu198, Ile231, Trp234, Val256, Tyr259, Val260 and the aliphatic portion of His230 (Fig. 3d,f and Supplementary Fig. 1g).	RESULTS
138	144	Trp234	residue_name_number	The aromatic ring of Phe285 on MKP7 α5-helix is nestled in a hydrophobic pocket on JNK1, formed by side chains of Ile197, Leu198, Ile231, Trp234, Val256, Tyr259, Val260 and the aliphatic portion of His230 (Fig. 3d,f and Supplementary Fig. 1g).	RESULTS
146	152	Val256	residue_name_number	The aromatic ring of Phe285 on MKP7 α5-helix is nestled in a hydrophobic pocket on JNK1, formed by side chains of Ile197, Leu198, Ile231, Trp234, Val256, Tyr259, Val260 and the aliphatic portion of His230 (Fig. 3d,f and Supplementary Fig. 1g).	RESULTS
154	160	Tyr259	residue_name_number	The aromatic ring of Phe285 on MKP7 α5-helix is nestled in a hydrophobic pocket on JNK1, formed by side chains of Ile197, Leu198, Ile231, Trp234, Val256, Tyr259, Val260 and the aliphatic portion of His230 (Fig. 3d,f and Supplementary Fig. 1g).	RESULTS
162	168	Val260	residue_name_number	The aromatic ring of Phe285 on MKP7 α5-helix is nestled in a hydrophobic pocket on JNK1, formed by side chains of Ile197, Leu198, Ile231, Trp234, Val256, Tyr259, Val260 and the aliphatic portion of His230 (Fig. 3d,f and Supplementary Fig. 1g).	RESULTS
198	204	His230	residue_name_number	The aromatic ring of Phe285 on MKP7 α5-helix is nestled in a hydrophobic pocket on JNK1, formed by side chains of Ile197, Leu198, Ile231, Trp234, Val256, Tyr259, Val260 and the aliphatic portion of His230 (Fig. 3d,f and Supplementary Fig. 1g).	RESULTS
23	37	hydrogen bonds	bond_interaction	In addition, there are hydrogen bonds between Ser282 and Asn286 of MKP7 and His230 and Thr255 of JNK1, and the main chain of Phe215 in the general acid loop of MKP7 is hydrogen-bonded to the side chain of Gln253 in JNK1.	RESULTS
46	52	Ser282	residue_name_number	In addition, there are hydrogen bonds between Ser282 and Asn286 of MKP7 and His230 and Thr255 of JNK1, and the main chain of Phe215 in the general acid loop of MKP7 is hydrogen-bonded to the side chain of Gln253 in JNK1.	RESULTS
57	63	Asn286	residue_name_number	In addition, there are hydrogen bonds between Ser282 and Asn286 of MKP7 and His230 and Thr255 of JNK1, and the main chain of Phe215 in the general acid loop of MKP7 is hydrogen-bonded to the side chain of Gln253 in JNK1.	RESULTS
67	71	MKP7	protein	In addition, there are hydrogen bonds between Ser282 and Asn286 of MKP7 and His230 and Thr255 of JNK1, and the main chain of Phe215 in the general acid loop of MKP7 is hydrogen-bonded to the side chain of Gln253 in JNK1.	RESULTS
76	82	His230	residue_name_number	In addition, there are hydrogen bonds between Ser282 and Asn286 of MKP7 and His230 and Thr255 of JNK1, and the main chain of Phe215 in the general acid loop of MKP7 is hydrogen-bonded to the side chain of Gln253 in JNK1.	RESULTS
87	93	Thr255	residue_name_number	In addition, there are hydrogen bonds between Ser282 and Asn286 of MKP7 and His230 and Thr255 of JNK1, and the main chain of Phe215 in the general acid loop of MKP7 is hydrogen-bonded to the side chain of Gln253 in JNK1.	RESULTS
97	101	JNK1	protein	In addition, there are hydrogen bonds between Ser282 and Asn286 of MKP7 and His230 and Thr255 of JNK1, and the main chain of Phe215 in the general acid loop of MKP7 is hydrogen-bonded to the side chain of Gln253 in JNK1.	RESULTS
125	131	Phe215	residue_name_number	In addition, there are hydrogen bonds between Ser282 and Asn286 of MKP7 and His230 and Thr255 of JNK1, and the main chain of Phe215 in the general acid loop of MKP7 is hydrogen-bonded to the side chain of Gln253 in JNK1.	RESULTS
139	156	general acid loop	structure_element	In addition, there are hydrogen bonds between Ser282 and Asn286 of MKP7 and His230 and Thr255 of JNK1, and the main chain of Phe215 in the general acid loop of MKP7 is hydrogen-bonded to the side chain of Gln253 in JNK1.	RESULTS
160	164	MKP7	protein	In addition, there are hydrogen bonds between Ser282 and Asn286 of MKP7 and His230 and Thr255 of JNK1, and the main chain of Phe215 in the general acid loop of MKP7 is hydrogen-bonded to the side chain of Gln253 in JNK1.	RESULTS
168	183	hydrogen-bonded	bond_interaction	In addition, there are hydrogen bonds between Ser282 and Asn286 of MKP7 and His230 and Thr255 of JNK1, and the main chain of Phe215 in the general acid loop of MKP7 is hydrogen-bonded to the side chain of Gln253 in JNK1.	RESULTS
205	211	Gln253	residue_name_number	In addition, there are hydrogen bonds between Ser282 and Asn286 of MKP7 and His230 and Thr255 of JNK1, and the main chain of Phe215 in the general acid loop of MKP7 is hydrogen-bonded to the side chain of Gln253 in JNK1.	RESULTS
215	219	JNK1	protein	In addition, there are hydrogen bonds between Ser282 and Asn286 of MKP7 and His230 and Thr255 of JNK1, and the main chain of Phe215 in the general acid loop of MKP7 is hydrogen-bonded to the side chain of Gln253 in JNK1.	RESULTS
4	27	second interactive area	site	The second interactive area involves the α4 helix of MKP7 and charged/polar residues of JNK1 (Fig. 3e).	RESULTS
41	49	α4 helix	structure_element	The second interactive area involves the α4 helix of MKP7 and charged/polar residues of JNK1 (Fig. 3e).	RESULTS
53	57	MKP7	protein	The second interactive area involves the α4 helix of MKP7 and charged/polar residues of JNK1 (Fig. 3e).	RESULTS
88	92	JNK1	protein	The second interactive area involves the α4 helix of MKP7 and charged/polar residues of JNK1 (Fig. 3e).	RESULTS
19	25	Asp268	residue_name_number	The carboxylate of Asp268 in MKP7 forms a salt bridge with side chain of Arg263 in JNK1, and Lys275 of MKP7 forms a hydrogen bond and a salt bridge with Thr228 and Asp229 of JNK1, respectively.	RESULTS
29	33	MKP7	protein	The carboxylate of Asp268 in MKP7 forms a salt bridge with side chain of Arg263 in JNK1, and Lys275 of MKP7 forms a hydrogen bond and a salt bridge with Thr228 and Asp229 of JNK1, respectively.	RESULTS
42	53	salt bridge	bond_interaction	The carboxylate of Asp268 in MKP7 forms a salt bridge with side chain of Arg263 in JNK1, and Lys275 of MKP7 forms a hydrogen bond and a salt bridge with Thr228 and Asp229 of JNK1, respectively.	RESULTS
73	79	Arg263	residue_name_number	The carboxylate of Asp268 in MKP7 forms a salt bridge with side chain of Arg263 in JNK1, and Lys275 of MKP7 forms a hydrogen bond and a salt bridge with Thr228 and Asp229 of JNK1, respectively.	RESULTS
83	87	JNK1	protein	The carboxylate of Asp268 in MKP7 forms a salt bridge with side chain of Arg263 in JNK1, and Lys275 of MKP7 forms a hydrogen bond and a salt bridge with Thr228 and Asp229 of JNK1, respectively.	RESULTS
93	99	Lys275	residue_name_number	The carboxylate of Asp268 in MKP7 forms a salt bridge with side chain of Arg263 in JNK1, and Lys275 of MKP7 forms a hydrogen bond and a salt bridge with Thr228 and Asp229 of JNK1, respectively.	RESULTS
103	107	MKP7	protein	The carboxylate of Asp268 in MKP7 forms a salt bridge with side chain of Arg263 in JNK1, and Lys275 of MKP7 forms a hydrogen bond and a salt bridge with Thr228 and Asp229 of JNK1, respectively.	RESULTS
116	129	hydrogen bond	bond_interaction	The carboxylate of Asp268 in MKP7 forms a salt bridge with side chain of Arg263 in JNK1, and Lys275 of MKP7 forms a hydrogen bond and a salt bridge with Thr228 and Asp229 of JNK1, respectively.	RESULTS
136	147	salt bridge	bond_interaction	The carboxylate of Asp268 in MKP7 forms a salt bridge with side chain of Arg263 in JNK1, and Lys275 of MKP7 forms a hydrogen bond and a salt bridge with Thr228 and Asp229 of JNK1, respectively.	RESULTS
153	159	Thr228	residue_name_number	The carboxylate of Asp268 in MKP7 forms a salt bridge with side chain of Arg263 in JNK1, and Lys275 of MKP7 forms a hydrogen bond and a salt bridge with Thr228 and Asp229 of JNK1, respectively.	RESULTS
164	170	Asp229	residue_name_number	The carboxylate of Asp268 in MKP7 forms a salt bridge with side chain of Arg263 in JNK1, and Lys275 of MKP7 forms a hydrogen bond and a salt bridge with Thr228 and Asp229 of JNK1, respectively.	RESULTS
174	178	JNK1	protein	The carboxylate of Asp268 in MKP7 forms a salt bridge with side chain of Arg263 in JNK1, and Lys275 of MKP7 forms a hydrogen bond and a salt bridge with Thr228 and Asp229 of JNK1, respectively.	RESULTS
0	19	Mutational analysis	experimental_method	Mutational analysis of the JNK1–MKP7 docking interface	RESULTS
27	54	JNK1–MKP7 docking interface	site	Mutational analysis of the JNK1–MKP7 docking interface	RESULTS
86	101	point mutations	experimental_method	To assess the importance of the aforementioned interactions, we generated a series of point mutations on the MKP7-CD and examined their effect on the MKP7-catalysed JNK1 dephosphorylation (Fig. 4a).	RESULTS
109	113	MKP7	protein	To assess the importance of the aforementioned interactions, we generated a series of point mutations on the MKP7-CD and examined their effect on the MKP7-catalysed JNK1 dephosphorylation (Fig. 4a).	RESULTS
114	116	CD	structure_element	To assess the importance of the aforementioned interactions, we generated a series of point mutations on the MKP7-CD and examined their effect on the MKP7-catalysed JNK1 dephosphorylation (Fig. 4a).	RESULTS
150	154	MKP7	protein	To assess the importance of the aforementioned interactions, we generated a series of point mutations on the MKP7-CD and examined their effect on the MKP7-catalysed JNK1 dephosphorylation (Fig. 4a).	RESULTS
165	169	JNK1	protein	To assess the importance of the aforementioned interactions, we generated a series of point mutations on the MKP7-CD and examined their effect on the MKP7-catalysed JNK1 dephosphorylation (Fig. 4a).	RESULTS
170	187	dephosphorylation	ptm	To assess the importance of the aforementioned interactions, we generated a series of point mutations on the MKP7-CD and examined their effect on the MKP7-catalysed JNK1 dephosphorylation (Fig. 4a).	RESULTS
30	36	Phe285	residue_name_number	When the hydrophobic residues Phe285 and Phe287 on the α5 of MKP7-CD were replaced by Asp or Ala, their phosphatase activities for JNK1 dephosphorylation decreased ∼10-fold.	RESULTS
41	47	Phe287	residue_name_number	When the hydrophobic residues Phe285 and Phe287 on the α5 of MKP7-CD were replaced by Asp or Ala, their phosphatase activities for JNK1 dephosphorylation decreased ∼10-fold.	RESULTS
55	57	α5	structure_element	When the hydrophobic residues Phe285 and Phe287 on the α5 of MKP7-CD were replaced by Asp or Ala, their phosphatase activities for JNK1 dephosphorylation decreased ∼10-fold.	RESULTS
61	65	MKP7	protein	When the hydrophobic residues Phe285 and Phe287 on the α5 of MKP7-CD were replaced by Asp or Ala, their phosphatase activities for JNK1 dephosphorylation decreased ∼10-fold.	RESULTS
66	68	CD	structure_element	When the hydrophobic residues Phe285 and Phe287 on the α5 of MKP7-CD were replaced by Asp or Ala, their phosphatase activities for JNK1 dephosphorylation decreased ∼10-fold.	RESULTS
74	82	replaced	experimental_method	When the hydrophobic residues Phe285 and Phe287 on the α5 of MKP7-CD were replaced by Asp or Ala, their phosphatase activities for JNK1 dephosphorylation decreased ∼10-fold.	RESULTS
86	89	Asp	residue_name	When the hydrophobic residues Phe285 and Phe287 on the α5 of MKP7-CD were replaced by Asp or Ala, their phosphatase activities for JNK1 dephosphorylation decreased ∼10-fold.	RESULTS
93	96	Ala	residue_name	When the hydrophobic residues Phe285 and Phe287 on the α5 of MKP7-CD were replaced by Asp or Ala, their phosphatase activities for JNK1 dephosphorylation decreased ∼10-fold.	RESULTS
131	135	JNK1	protein	When the hydrophobic residues Phe285 and Phe287 on the α5 of MKP7-CD were replaced by Asp or Ala, their phosphatase activities for JNK1 dephosphorylation decreased ∼10-fold.	RESULTS
136	153	dephosphorylation	ptm	When the hydrophobic residues Phe285 and Phe287 on the α5 of MKP7-CD were replaced by Asp or Ala, their phosphatase activities for JNK1 dephosphorylation decreased ∼10-fold.	RESULTS
15	26	replacement	experimental_method	In comparison, replacement of the other residues (Phe215, Asp268, Lys275, Ser282, Asn286 and Leu292) with an Ala or Asp individually led to a modest decrease in catalytic efficiencies, suggesting that this position may only affect some selectivity of MKP.	RESULTS
50	56	Phe215	residue_name_number	In comparison, replacement of the other residues (Phe215, Asp268, Lys275, Ser282, Asn286 and Leu292) with an Ala or Asp individually led to a modest decrease in catalytic efficiencies, suggesting that this position may only affect some selectivity of MKP.	RESULTS
58	64	Asp268	residue_name_number	In comparison, replacement of the other residues (Phe215, Asp268, Lys275, Ser282, Asn286 and Leu292) with an Ala or Asp individually led to a modest decrease in catalytic efficiencies, suggesting that this position may only affect some selectivity of MKP.	RESULTS
66	72	Lys275	residue_name_number	In comparison, replacement of the other residues (Phe215, Asp268, Lys275, Ser282, Asn286 and Leu292) with an Ala or Asp individually led to a modest decrease in catalytic efficiencies, suggesting that this position may only affect some selectivity of MKP.	RESULTS
74	80	Ser282	residue_name_number	In comparison, replacement of the other residues (Phe215, Asp268, Lys275, Ser282, Asn286 and Leu292) with an Ala or Asp individually led to a modest decrease in catalytic efficiencies, suggesting that this position may only affect some selectivity of MKP.	RESULTS
82	88	Asn286	residue_name_number	In comparison, replacement of the other residues (Phe215, Asp268, Lys275, Ser282, Asn286 and Leu292) with an Ala or Asp individually led to a modest decrease in catalytic efficiencies, suggesting that this position may only affect some selectivity of MKP.	RESULTS
93	99	Leu292	residue_name_number	In comparison, replacement of the other residues (Phe215, Asp268, Lys275, Ser282, Asn286 and Leu292) with an Ala or Asp individually led to a modest decrease in catalytic efficiencies, suggesting that this position may only affect some selectivity of MKP.	RESULTS
109	112	Ala	residue_name	In comparison, replacement of the other residues (Phe215, Asp268, Lys275, Ser282, Asn286 and Leu292) with an Ala or Asp individually led to a modest decrease in catalytic efficiencies, suggesting that this position may only affect some selectivity of MKP.	RESULTS
116	119	Asp	residue_name	In comparison, replacement of the other residues (Phe215, Asp268, Lys275, Ser282, Asn286 and Leu292) with an Ala or Asp individually led to a modest decrease in catalytic efficiencies, suggesting that this position may only affect some selectivity of MKP.	RESULTS
251	254	MKP	protein_type	In comparison, replacement of the other residues (Phe215, Asp268, Lys275, Ser282, Asn286 and Leu292) with an Ala or Asp individually led to a modest decrease in catalytic efficiencies, suggesting that this position may only affect some selectivity of MKP.	RESULTS
0	8	Mutation	experimental_method	Mutation of Leu288 markedly reduced its solubility when expressed in Escherichia coli, resulting in the insoluble aggregation of the mutant protein.	RESULTS
12	18	Leu288	residue_name_number	Mutation of Leu288 markedly reduced its solubility when expressed in Escherichia coli, resulting in the insoluble aggregation of the mutant protein.	RESULTS
69	85	Escherichia coli	species	Mutation of Leu288 markedly reduced its solubility when expressed in Escherichia coli, resulting in the insoluble aggregation of the mutant protein.	RESULTS
133	139	mutant	protein_state	Mutation of Leu288 markedly reduced its solubility when expressed in Escherichia coli, resulting in the insoluble aggregation of the mutant protein.	RESULTS
0	23	Gel filtration analysis	experimental_method	Gel filtration analysis further confirmed the key role of Phe285 in the MKP7–JNK1 interaction: no F285D–JNK1 complex was detected when 3 molar equivalents of MKP7-CD (F285D) were mixed with 1 molar equivalent of JNK1 (Fig. 4b).	RESULTS
58	64	Phe285	residue_name_number	Gel filtration analysis further confirmed the key role of Phe285 in the MKP7–JNK1 interaction: no F285D–JNK1 complex was detected when 3 molar equivalents of MKP7-CD (F285D) were mixed with 1 molar equivalent of JNK1 (Fig. 4b).	RESULTS
72	76	MKP7	protein	Gel filtration analysis further confirmed the key role of Phe285 in the MKP7–JNK1 interaction: no F285D–JNK1 complex was detected when 3 molar equivalents of MKP7-CD (F285D) were mixed with 1 molar equivalent of JNK1 (Fig. 4b).	RESULTS
77	81	JNK1	protein	Gel filtration analysis further confirmed the key role of Phe285 in the MKP7–JNK1 interaction: no F285D–JNK1 complex was detected when 3 molar equivalents of MKP7-CD (F285D) were mixed with 1 molar equivalent of JNK1 (Fig. 4b).	RESULTS
98	108	F285D–JNK1	complex_assembly	Gel filtration analysis further confirmed the key role of Phe285 in the MKP7–JNK1 interaction: no F285D–JNK1 complex was detected when 3 molar equivalents of MKP7-CD (F285D) were mixed with 1 molar equivalent of JNK1 (Fig. 4b).	RESULTS
158	162	MKP7	protein	Gel filtration analysis further confirmed the key role of Phe285 in the MKP7–JNK1 interaction: no F285D–JNK1 complex was detected when 3 molar equivalents of MKP7-CD (F285D) were mixed with 1 molar equivalent of JNK1 (Fig. 4b).	RESULTS
163	165	CD	structure_element	Gel filtration analysis further confirmed the key role of Phe285 in the MKP7–JNK1 interaction: no F285D–JNK1 complex was detected when 3 molar equivalents of MKP7-CD (F285D) were mixed with 1 molar equivalent of JNK1 (Fig. 4b).	RESULTS
167	172	F285D	mutant	Gel filtration analysis further confirmed the key role of Phe285 in the MKP7–JNK1 interaction: no F285D–JNK1 complex was detected when 3 molar equivalents of MKP7-CD (F285D) were mixed with 1 molar equivalent of JNK1 (Fig. 4b).	RESULTS
212	216	JNK1	protein	Gel filtration analysis further confirmed the key role of Phe285 in the MKP7–JNK1 interaction: no F285D–JNK1 complex was detected when 3 molar equivalents of MKP7-CD (F285D) were mixed with 1 molar equivalent of JNK1 (Fig. 4b).	RESULTS
15	23	mutation	experimental_method	Interestingly, mutation of Phe287 results in a considerable loss of activity against pJNK1 without altering the affinity of MKP7-CD for JNK1 (Supplementary Fig. 2a).	RESULTS
27	33	Phe287	residue_name_number	Interestingly, mutation of Phe287 results in a considerable loss of activity against pJNK1 without altering the affinity of MKP7-CD for JNK1 (Supplementary Fig. 2a).	RESULTS
85	86	p	protein_state	Interestingly, mutation of Phe287 results in a considerable loss of activity against pJNK1 without altering the affinity of MKP7-CD for JNK1 (Supplementary Fig. 2a).	RESULTS
86	90	JNK1	protein	Interestingly, mutation of Phe287 results in a considerable loss of activity against pJNK1 without altering the affinity of MKP7-CD for JNK1 (Supplementary Fig. 2a).	RESULTS
112	120	affinity	evidence	Interestingly, mutation of Phe287 results in a considerable loss of activity against pJNK1 without altering the affinity of MKP7-CD for JNK1 (Supplementary Fig. 2a).	RESULTS
124	128	MKP7	protein	Interestingly, mutation of Phe287 results in a considerable loss of activity against pJNK1 without altering the affinity of MKP7-CD for JNK1 (Supplementary Fig. 2a).	RESULTS
129	131	CD	structure_element	Interestingly, mutation of Phe287 results in a considerable loss of activity against pJNK1 without altering the affinity of MKP7-CD for JNK1 (Supplementary Fig. 2a).	RESULTS
136	140	JNK1	protein	Interestingly, mutation of Phe287 results in a considerable loss of activity against pJNK1 without altering the affinity of MKP7-CD for JNK1 (Supplementary Fig. 2a).	RESULTS
30	45	point mutations	experimental_method	We also generated a series of point mutations in the JNK1 and assessed the effect on JNK1 binding using the GST pull-down assay (Fig. 4c).	RESULTS
53	57	JNK1	protein	We also generated a series of point mutations in the JNK1 and assessed the effect on JNK1 binding using the GST pull-down assay (Fig. 4c).	RESULTS
85	89	JNK1	protein	We also generated a series of point mutations in the JNK1 and assessed the effect on JNK1 binding using the GST pull-down assay (Fig. 4c).	RESULTS
108	127	GST pull-down assay	experimental_method	We also generated a series of point mutations in the JNK1 and assessed the effect on JNK1 binding using the GST pull-down assay (Fig. 4c).	RESULTS
0	12	Substitution	experimental_method	Substitution at Asp229, Trp234, Thr255, Val256, Tyr259 and Val260 significantly reduced the binding affinity of MKP7-CD for JNK.	RESULTS
16	22	Asp229	residue_name_number	Substitution at Asp229, Trp234, Thr255, Val256, Tyr259 and Val260 significantly reduced the binding affinity of MKP7-CD for JNK.	RESULTS
24	30	Trp234	residue_name_number	Substitution at Asp229, Trp234, Thr255, Val256, Tyr259 and Val260 significantly reduced the binding affinity of MKP7-CD for JNK.	RESULTS
32	38	Thr255	residue_name_number	Substitution at Asp229, Trp234, Thr255, Val256, Tyr259 and Val260 significantly reduced the binding affinity of MKP7-CD for JNK.	RESULTS
40	46	Val256	residue_name_number	Substitution at Asp229, Trp234, Thr255, Val256, Tyr259 and Val260 significantly reduced the binding affinity of MKP7-CD for JNK.	RESULTS
48	54	Tyr259	residue_name_number	Substitution at Asp229, Trp234, Thr255, Val256, Tyr259 and Val260 significantly reduced the binding affinity of MKP7-CD for JNK.	RESULTS
59	65	Val260	residue_name_number	Substitution at Asp229, Trp234, Thr255, Val256, Tyr259 and Val260 significantly reduced the binding affinity of MKP7-CD for JNK.	RESULTS
92	108	binding affinity	evidence	Substitution at Asp229, Trp234, Thr255, Val256, Tyr259 and Val260 significantly reduced the binding affinity of MKP7-CD for JNK.	RESULTS
112	116	MKP7	protein	Substitution at Asp229, Trp234, Thr255, Val256, Tyr259 and Val260 significantly reduced the binding affinity of MKP7-CD for JNK.	RESULTS
117	119	CD	structure_element	Substitution at Asp229, Trp234, Thr255, Val256, Tyr259 and Val260 significantly reduced the binding affinity of MKP7-CD for JNK.	RESULTS
124	127	JNK	protein_type	Substitution at Asp229, Trp234, Thr255, Val256, Tyr259 and Val260 significantly reduced the binding affinity of MKP7-CD for JNK.	RESULTS
154	160	mutant	protein_state	To determine whether the deficiencies in their abilities to bind partner proteins or carry out catalytic function are owing to misfolding of the purified mutant proteins, we also examined the folding properties of the JNK1 and MKP7 mutants with circular dichroism.	RESULTS
218	222	JNK1	protein	To determine whether the deficiencies in their abilities to bind partner proteins or carry out catalytic function are owing to misfolding of the purified mutant proteins, we also examined the folding properties of the JNK1 and MKP7 mutants with circular dichroism.	RESULTS
227	231	MKP7	protein	To determine whether the deficiencies in their abilities to bind partner proteins or carry out catalytic function are owing to misfolding of the purified mutant proteins, we also examined the folding properties of the JNK1 and MKP7 mutants with circular dichroism.	RESULTS
232	239	mutants	protein_state	To determine whether the deficiencies in their abilities to bind partner proteins or carry out catalytic function are owing to misfolding of the purified mutant proteins, we also examined the folding properties of the JNK1 and MKP7 mutants with circular dichroism.	RESULTS
245	263	circular dichroism	experimental_method	To determine whether the deficiencies in their abilities to bind partner proteins or carry out catalytic function are owing to misfolding of the purified mutant proteins, we also examined the folding properties of the JNK1 and MKP7 mutants with circular dichroism.	RESULTS
4	11	spectra	evidence	The spectra of these mutants are similar to the wild-type proteins, indicating that these mutants fold as well as the wild-type proteins (Fig. 4d,e).	RESULTS
21	28	mutants	protein_state	The spectra of these mutants are similar to the wild-type proteins, indicating that these mutants fold as well as the wild-type proteins (Fig. 4d,e).	RESULTS
48	57	wild-type	protein_state	The spectra of these mutants are similar to the wild-type proteins, indicating that these mutants fold as well as the wild-type proteins (Fig. 4d,e).	RESULTS
90	97	mutants	protein_state	The spectra of these mutants are similar to the wild-type proteins, indicating that these mutants fold as well as the wild-type proteins (Fig. 4d,e).	RESULTS
118	127	wild-type	protein_state	The spectra of these mutants are similar to the wild-type proteins, indicating that these mutants fold as well as the wild-type proteins (Fig. 4d,e).	RESULTS
62	84	crystallographic model	evidence	Taken together, these results are consistent with the present crystallographic model, which reveal the hydrophobic contacts between the MKP7 catalytic domain and JNK1 have a predominant role in the enzyme–substrate interaction, and hydrophobic residue Phe285 in the MKP7-CD is a key residue for its high-affinity binding to JNK1.	RESULTS
103	123	hydrophobic contacts	bond_interaction	Taken together, these results are consistent with the present crystallographic model, which reveal the hydrophobic contacts between the MKP7 catalytic domain and JNK1 have a predominant role in the enzyme–substrate interaction, and hydrophobic residue Phe285 in the MKP7-CD is a key residue for its high-affinity binding to JNK1.	RESULTS
136	140	MKP7	protein	Taken together, these results are consistent with the present crystallographic model, which reveal the hydrophobic contacts between the MKP7 catalytic domain and JNK1 have a predominant role in the enzyme–substrate interaction, and hydrophobic residue Phe285 in the MKP7-CD is a key residue for its high-affinity binding to JNK1.	RESULTS
141	157	catalytic domain	structure_element	Taken together, these results are consistent with the present crystallographic model, which reveal the hydrophobic contacts between the MKP7 catalytic domain and JNK1 have a predominant role in the enzyme–substrate interaction, and hydrophobic residue Phe285 in the MKP7-CD is a key residue for its high-affinity binding to JNK1.	RESULTS
162	166	JNK1	protein	Taken together, these results are consistent with the present crystallographic model, which reveal the hydrophobic contacts between the MKP7 catalytic domain and JNK1 have a predominant role in the enzyme–substrate interaction, and hydrophobic residue Phe285 in the MKP7-CD is a key residue for its high-affinity binding to JNK1.	RESULTS
252	258	Phe285	residue_name_number	Taken together, these results are consistent with the present crystallographic model, which reveal the hydrophobic contacts between the MKP7 catalytic domain and JNK1 have a predominant role in the enzyme–substrate interaction, and hydrophobic residue Phe285 in the MKP7-CD is a key residue for its high-affinity binding to JNK1.	RESULTS
266	270	MKP7	protein	Taken together, these results are consistent with the present crystallographic model, which reveal the hydrophobic contacts between the MKP7 catalytic domain and JNK1 have a predominant role in the enzyme–substrate interaction, and hydrophobic residue Phe285 in the MKP7-CD is a key residue for its high-affinity binding to JNK1.	RESULTS
271	273	CD	structure_element	Taken together, these results are consistent with the present crystallographic model, which reveal the hydrophobic contacts between the MKP7 catalytic domain and JNK1 have a predominant role in the enzyme–substrate interaction, and hydrophobic residue Phe285 in the MKP7-CD is a key residue for its high-affinity binding to JNK1.	RESULTS
324	328	JNK1	protein	Taken together, these results are consistent with the present crystallographic model, which reveal the hydrophobic contacts between the MKP7 catalytic domain and JNK1 have a predominant role in the enzyme–substrate interaction, and hydrophobic residue Phe285 in the MKP7-CD is a key residue for its high-affinity binding to JNK1.	RESULTS
77	81	MKPs	protein_type	It has previously been reported that several cytosolic and inducible nuclear MKPs undergo catalytic activation upon interaction with the MAPK substrates.	RESULTS
137	141	MAPK	protein_type	It has previously been reported that several cytosolic and inducible nuclear MKPs undergo catalytic activation upon interaction with the MAPK substrates.	RESULTS
30	34	MKP3	protein	This allosteric activation of MKP3 has been well-documented in vitro using pNPP, a small-molecule phosphotyrosine analogue of its normal substrate.	RESULTS
75	79	pNPP	chemical	This allosteric activation of MKP3 has been well-documented in vitro using pNPP, a small-molecule phosphotyrosine analogue of its normal substrate.	RESULTS
98	113	phosphotyrosine	residue_name	This allosteric activation of MKP3 has been well-documented in vitro using pNPP, a small-molecule phosphotyrosine analogue of its normal substrate.	RESULTS
16	23	pNPPase	protein_type	We then assayed pNPPase activities of MKP7ΔC304 and MKP7-CD in the presence of JNK1.	RESULTS
38	47	MKP7ΔC304	mutant	We then assayed pNPPase activities of MKP7ΔC304 and MKP7-CD in the presence of JNK1.	RESULTS
52	56	MKP7	protein	We then assayed pNPPase activities of MKP7ΔC304 and MKP7-CD in the presence of JNK1.	RESULTS
57	59	CD	structure_element	We then assayed pNPPase activities of MKP7ΔC304 and MKP7-CD in the presence of JNK1.	RESULTS
67	78	presence of	protein_state	We then assayed pNPPase activities of MKP7ΔC304 and MKP7-CD in the presence of JNK1.	RESULTS
79	83	JNK1	protein	We then assayed pNPPase activities of MKP7ΔC304 and MKP7-CD in the presence of JNK1.	RESULTS
0	10	Incubation	experimental_method	Incubation of MKP7 with JNK1 did not markedly stimulate the phosphatase activity, which is consistent with previous results that MKP7 solely possesses the intrinsic activity (Supplementary Fig. 2b).	RESULTS
14	18	MKP7	protein	Incubation of MKP7 with JNK1 did not markedly stimulate the phosphatase activity, which is consistent with previous results that MKP7 solely possesses the intrinsic activity (Supplementary Fig. 2b).	RESULTS
24	28	JNK1	protein	Incubation of MKP7 with JNK1 did not markedly stimulate the phosphatase activity, which is consistent with previous results that MKP7 solely possesses the intrinsic activity (Supplementary Fig. 2b).	RESULTS
60	71	phosphatase	protein_type	Incubation of MKP7 with JNK1 did not markedly stimulate the phosphatase activity, which is consistent with previous results that MKP7 solely possesses the intrinsic activity (Supplementary Fig. 2b).	RESULTS
129	133	MKP7	protein	Incubation of MKP7 with JNK1 did not markedly stimulate the phosphatase activity, which is consistent with previous results that MKP7 solely possesses the intrinsic activity (Supplementary Fig. 2b).	RESULTS
10	14	pNPP	chemical	The small pNPP molecule binds directly at the enzyme active site and can be used to probe the reaction mechanism of protein phosphatases.	RESULTS
53	64	active site	site	The small pNPP molecule binds directly at the enzyme active site and can be used to probe the reaction mechanism of protein phosphatases.	RESULTS
116	136	protein phosphatases	protein_type	The small pNPP molecule binds directly at the enzyme active site and can be used to probe the reaction mechanism of protein phosphatases.	RESULTS
41	45	MKP7	protein	We therefore examined the effects of the MKP7-CD mutants on their pNPPase activities.	RESULTS
46	48	CD	structure_element	We therefore examined the effects of the MKP7-CD mutants on their pNPPase activities.	RESULTS
49	56	mutants	protein_state	We therefore examined the effects of the MKP7-CD mutants on their pNPPase activities.	RESULTS
66	73	pNPPase	protein_type	We therefore examined the effects of the MKP7-CD mutants on their pNPPase activities.	RESULTS
29	36	mutants	protein_state	As shown in Fig. 4f, all the mutants, except F287D/A, showed little or no activity change compared with the wild-type MKP7-CD.	RESULTS
45	52	F287D/A	mutant	As shown in Fig. 4f, all the mutants, except F287D/A, showed little or no activity change compared with the wild-type MKP7-CD.	RESULTS
108	117	wild-type	protein_state	As shown in Fig. 4f, all the mutants, except F287D/A, showed little or no activity change compared with the wild-type MKP7-CD.	RESULTS
118	122	MKP7	protein	As shown in Fig. 4f, all the mutants, except F287D/A, showed little or no activity change compared with the wild-type MKP7-CD.	RESULTS
123	125	CD	structure_element	As shown in Fig. 4f, all the mutants, except F287D/A, showed little or no activity change compared with the wild-type MKP7-CD.	RESULTS
7	19	JNK1/MKP7-CD	complex_assembly	In the JNK1/MKP7-CD complex structure, Phe287 of MKP7 does not make contacts with JNK1 substrate.	RESULTS
28	37	structure	evidence	In the JNK1/MKP7-CD complex structure, Phe287 of MKP7 does not make contacts with JNK1 substrate.	RESULTS
39	45	Phe287	residue_name_number	In the JNK1/MKP7-CD complex structure, Phe287 of MKP7 does not make contacts with JNK1 substrate.	RESULTS
49	53	MKP7	protein	In the JNK1/MKP7-CD complex structure, Phe287 of MKP7 does not make contacts with JNK1 substrate.	RESULTS
82	86	JNK1	protein	In the JNK1/MKP7-CD complex structure, Phe287 of MKP7 does not make contacts with JNK1 substrate.	RESULTS
21	27	pocket	site	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
56	62	P-loop	structure_element	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
67	84	general acid loop	structure_element	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
95	115	hydrophobic contacts	bond_interaction	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
162	168	Arg250	residue_name_number	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
170	176	Glu217	residue_name_number	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
181	187	Ile219	residue_name_number	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
205	211	Phe287	residue_name_number	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
215	219	MKP7	protein	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
291	295	PTPs	protein_type	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
297	303	Gln266	residue_name_number	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
307	312	PTP1B	protein	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
318	321	VHR	protein	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
323	329	Phe166	residue_name_number	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
333	336	VHR	protein	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
366	386	active-site residues	site	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
390	394	MKP7	protein	It penetrates into a pocket formed by residues from the P-loop and general acid loop and forms hydrophobic contacts with the aliphatic portions of side chains of Arg250, Glu217 and Ile219, suggesting that Phe287 in MKP7 would play a similar role to that of its structural counterpart in the PTPs (Gln266 in PTP1B) and VHR (Phe166 in VHR) in the precise alignment of active-site residues in MKP7 with respect to the substrate for efficient catalysis (Supplementary Fig. 2c).	RESULTS
0	29	Kinase-associated phosphatase	protein	Kinase-associated phosphatase (KAP), a member of the DUSP family, plays a crucial role in cell cycle regulation by dephosphorylating the pThr160 residue of CDK2 (cyclin-dependent kinase 2).	RESULTS
31	34	KAP	protein	Kinase-associated phosphatase (KAP), a member of the DUSP family, plays a crucial role in cell cycle regulation by dephosphorylating the pThr160 residue of CDK2 (cyclin-dependent kinase 2).	RESULTS
53	64	DUSP family	protein_type	Kinase-associated phosphatase (KAP), a member of the DUSP family, plays a crucial role in cell cycle regulation by dephosphorylating the pThr160 residue of CDK2 (cyclin-dependent kinase 2).	RESULTS
137	144	pThr160	ptm	Kinase-associated phosphatase (KAP), a member of the DUSP family, plays a crucial role in cell cycle regulation by dephosphorylating the pThr160 residue of CDK2 (cyclin-dependent kinase 2).	RESULTS
156	160	CDK2	protein	Kinase-associated phosphatase (KAP), a member of the DUSP family, plays a crucial role in cell cycle regulation by dephosphorylating the pThr160 residue of CDK2 (cyclin-dependent kinase 2).	RESULTS
162	187	cyclin-dependent kinase 2	protein	Kinase-associated phosphatase (KAP), a member of the DUSP family, plays a crucial role in cell cycle regulation by dephosphorylating the pThr160 residue of CDK2 (cyclin-dependent kinase 2).	RESULTS
4	21	crystal structure	evidence	The crystal structure of the CDK2/KAP complex has been determined at 3.0 Å (Fig. 5a).	RESULTS
29	37	CDK2/KAP	complex_assembly	The crystal structure of the CDK2/KAP complex has been determined at 3.0 Å (Fig. 5a).	RESULTS
4	13	interface	site	The interface between these two proteins consists of three discontinuous contact regions.	RESULTS
72	75	KAP	protein	Biochemical results suggested that the affinity and specificity between KAP and CDK2 results from the recognition site comprising CDK2 residues from the αG helix and L14 loop and the N-terminal helical region of KAP (Fig. 5b).	RESULTS
80	84	CDK2	protein	Biochemical results suggested that the affinity and specificity between KAP and CDK2 results from the recognition site comprising CDK2 residues from the αG helix and L14 loop and the N-terminal helical region of KAP (Fig. 5b).	RESULTS
102	118	recognition site	site	Biochemical results suggested that the affinity and specificity between KAP and CDK2 results from the recognition site comprising CDK2 residues from the αG helix and L14 loop and the N-terminal helical region of KAP (Fig. 5b).	RESULTS
130	134	CDK2	protein	Biochemical results suggested that the affinity and specificity between KAP and CDK2 results from the recognition site comprising CDK2 residues from the αG helix and L14 loop and the N-terminal helical region of KAP (Fig. 5b).	RESULTS
153	161	αG helix	structure_element	Biochemical results suggested that the affinity and specificity between KAP and CDK2 results from the recognition site comprising CDK2 residues from the αG helix and L14 loop and the N-terminal helical region of KAP (Fig. 5b).	RESULTS
166	174	L14 loop	structure_element	Biochemical results suggested that the affinity and specificity between KAP and CDK2 results from the recognition site comprising CDK2 residues from the αG helix and L14 loop and the N-terminal helical region of KAP (Fig. 5b).	RESULTS
183	208	N-terminal helical region	structure_element	Biochemical results suggested that the affinity and specificity between KAP and CDK2 results from the recognition site comprising CDK2 residues from the αG helix and L14 loop and the N-terminal helical region of KAP (Fig. 5b).	RESULTS
212	215	KAP	protein	Biochemical results suggested that the affinity and specificity between KAP and CDK2 results from the recognition site comprising CDK2 residues from the αG helix and L14 loop and the N-terminal helical region of KAP (Fig. 5b).	RESULTS
11	24	hydrogen bond	bond_interaction	There is a hydrogen bond between the main-chain nitrogen of Ile183 (KAP) and side chain oxygen of Glu208 (CDK2), and salt bridges between Lys184 of KAP and Asp235 of CDK2.	RESULTS
60	66	Ile183	residue_name_number	There is a hydrogen bond between the main-chain nitrogen of Ile183 (KAP) and side chain oxygen of Glu208 (CDK2), and salt bridges between Lys184 of KAP and Asp235 of CDK2.	RESULTS
68	71	KAP	protein	There is a hydrogen bond between the main-chain nitrogen of Ile183 (KAP) and side chain oxygen of Glu208 (CDK2), and salt bridges between Lys184 of KAP and Asp235 of CDK2.	RESULTS
98	104	Glu208	residue_name_number	There is a hydrogen bond between the main-chain nitrogen of Ile183 (KAP) and side chain oxygen of Glu208 (CDK2), and salt bridges between Lys184 of KAP and Asp235 of CDK2.	RESULTS
106	110	CDK2	protein	There is a hydrogen bond between the main-chain nitrogen of Ile183 (KAP) and side chain oxygen of Glu208 (CDK2), and salt bridges between Lys184 of KAP and Asp235 of CDK2.	RESULTS
138	144	Lys184	residue_name_number	There is a hydrogen bond between the main-chain nitrogen of Ile183 (KAP) and side chain oxygen of Glu208 (CDK2), and salt bridges between Lys184 of KAP and Asp235 of CDK2.	RESULTS
148	151	KAP	protein	There is a hydrogen bond between the main-chain nitrogen of Ile183 (KAP) and side chain oxygen of Glu208 (CDK2), and salt bridges between Lys184 of KAP and Asp235 of CDK2.	RESULTS
156	162	Asp235	residue_name_number	There is a hydrogen bond between the main-chain nitrogen of Ile183 (KAP) and side chain oxygen of Glu208 (CDK2), and salt bridges between Lys184 of KAP and Asp235 of CDK2.	RESULTS
166	170	CDK2	protein	There is a hydrogen bond between the main-chain nitrogen of Ile183 (KAP) and side chain oxygen of Glu208 (CDK2), and salt bridges between Lys184 of KAP and Asp235 of CDK2.	RESULTS
0	19	Structural analysis	experimental_method	Structural analysis and sequence alignment reveal that one of the few differences between MKP7-CD and KAP in the substrate-binding region is the presence of the motif FNFL in MKP7-CD, which corresponds to IKQY in KAP (Fig. 5c).	RESULTS
24	42	sequence alignment	experimental_method	Structural analysis and sequence alignment reveal that one of the few differences between MKP7-CD and KAP in the substrate-binding region is the presence of the motif FNFL in MKP7-CD, which corresponds to IKQY in KAP (Fig. 5c).	RESULTS
90	94	MKP7	protein	Structural analysis and sequence alignment reveal that one of the few differences between MKP7-CD and KAP in the substrate-binding region is the presence of the motif FNFL in MKP7-CD, which corresponds to IKQY in KAP (Fig. 5c).	RESULTS
95	97	CD	structure_element	Structural analysis and sequence alignment reveal that one of the few differences between MKP7-CD and KAP in the substrate-binding region is the presence of the motif FNFL in MKP7-CD, which corresponds to IKQY in KAP (Fig. 5c).	RESULTS
102	105	KAP	protein	Structural analysis and sequence alignment reveal that one of the few differences between MKP7-CD and KAP in the substrate-binding region is the presence of the motif FNFL in MKP7-CD, which corresponds to IKQY in KAP (Fig. 5c).	RESULTS
113	137	substrate-binding region	site	Structural analysis and sequence alignment reveal that one of the few differences between MKP7-CD and KAP in the substrate-binding region is the presence of the motif FNFL in MKP7-CD, which corresponds to IKQY in KAP (Fig. 5c).	RESULTS
167	171	FNFL	structure_element	Structural analysis and sequence alignment reveal that one of the few differences between MKP7-CD and KAP in the substrate-binding region is the presence of the motif FNFL in MKP7-CD, which corresponds to IKQY in KAP (Fig. 5c).	RESULTS
175	179	MKP7	protein	Structural analysis and sequence alignment reveal that one of the few differences between MKP7-CD and KAP in the substrate-binding region is the presence of the motif FNFL in MKP7-CD, which corresponds to IKQY in KAP (Fig. 5c).	RESULTS
180	182	CD	structure_element	Structural analysis and sequence alignment reveal that one of the few differences between MKP7-CD and KAP in the substrate-binding region is the presence of the motif FNFL in MKP7-CD, which corresponds to IKQY in KAP (Fig. 5c).	RESULTS
205	209	IKQY	structure_element	Structural analysis and sequence alignment reveal that one of the few differences between MKP7-CD and KAP in the substrate-binding region is the presence of the motif FNFL in MKP7-CD, which corresponds to IKQY in KAP (Fig. 5c).	RESULTS
213	216	KAP	protein	Structural analysis and sequence alignment reveal that one of the few differences between MKP7-CD and KAP in the substrate-binding region is the presence of the motif FNFL in MKP7-CD, which corresponds to IKQY in KAP (Fig. 5c).	RESULTS
4	16	substitution	experimental_method	The substitution of the two hydrophobic residues with charged/polar residues (F285I/N286K) seriously disrupts the hydrophobic interaction required for MKP7 binding on JNK1 (Fig. 4a).	RESULTS
78	83	F285I	mutant	The substitution of the two hydrophobic residues with charged/polar residues (F285I/N286K) seriously disrupts the hydrophobic interaction required for MKP7 binding on JNK1 (Fig. 4a).	RESULTS
84	89	N286K	mutant	The substitution of the two hydrophobic residues with charged/polar residues (F285I/N286K) seriously disrupts the hydrophobic interaction required for MKP7 binding on JNK1 (Fig. 4a).	RESULTS
114	137	hydrophobic interaction	bond_interaction	The substitution of the two hydrophobic residues with charged/polar residues (F285I/N286K) seriously disrupts the hydrophobic interaction required for MKP7 binding on JNK1 (Fig. 4a).	RESULTS
151	155	MKP7	protein	The substitution of the two hydrophobic residues with charged/polar residues (F285I/N286K) seriously disrupts the hydrophobic interaction required for MKP7 binding on JNK1 (Fig. 4a).	RESULTS
167	171	JNK1	protein	The substitution of the two hydrophobic residues with charged/polar residues (F285I/N286K) seriously disrupts the hydrophobic interaction required for MKP7 binding on JNK1 (Fig. 4a).	RESULTS
13	19	His230	residue_name_number	In addition, His230 and Val256 in JNK1 are replaced by the negatively charged residues Glu208 and Asp235 in CDK2 (Fig. 5d), and the charge distribution on the CDK2 interactive surface is quite different from that of JNK.	RESULTS
24	30	Val256	residue_name_number	In addition, His230 and Val256 in JNK1 are replaced by the negatively charged residues Glu208 and Asp235 in CDK2 (Fig. 5d), and the charge distribution on the CDK2 interactive surface is quite different from that of JNK.	RESULTS
34	38	JNK1	protein	In addition, His230 and Val256 in JNK1 are replaced by the negatively charged residues Glu208 and Asp235 in CDK2 (Fig. 5d), and the charge distribution on the CDK2 interactive surface is quite different from that of JNK.	RESULTS
87	93	Glu208	residue_name_number	In addition, His230 and Val256 in JNK1 are replaced by the negatively charged residues Glu208 and Asp235 in CDK2 (Fig. 5d), and the charge distribution on the CDK2 interactive surface is quite different from that of JNK.	RESULTS
98	104	Asp235	residue_name_number	In addition, His230 and Val256 in JNK1 are replaced by the negatively charged residues Glu208 and Asp235 in CDK2 (Fig. 5d), and the charge distribution on the CDK2 interactive surface is quite different from that of JNK.	RESULTS
108	112	CDK2	protein	In addition, His230 and Val256 in JNK1 are replaced by the negatively charged residues Glu208 and Asp235 in CDK2 (Fig. 5d), and the charge distribution on the CDK2 interactive surface is quite different from that of JNK.	RESULTS
159	163	CDK2	protein	In addition, His230 and Val256 in JNK1 are replaced by the negatively charged residues Glu208 and Asp235 in CDK2 (Fig. 5d), and the charge distribution on the CDK2 interactive surface is quite different from that of JNK.	RESULTS
164	183	interactive surface	site	In addition, His230 and Val256 in JNK1 are replaced by the negatively charged residues Glu208 and Asp235 in CDK2 (Fig. 5d), and the charge distribution on the CDK2 interactive surface is quite different from that of JNK.	RESULTS
216	219	JNK	protein_type	In addition, His230 and Val256 in JNK1 are replaced by the negatively charged residues Glu208 and Asp235 in CDK2 (Fig. 5d), and the charge distribution on the CDK2 interactive surface is quite different from that of JNK.	RESULTS
35	53	hydrophobic pocket	site	These data indicated that a unique hydrophobic pocket formed between the MAPK insert and αG helix plays a major role in the substrate recognition by MKPs.	RESULTS
73	84	MAPK insert	structure_element	These data indicated that a unique hydrophobic pocket formed between the MAPK insert and αG helix plays a major role in the substrate recognition by MKPs.	RESULTS
89	97	αG helix	structure_element	These data indicated that a unique hydrophobic pocket formed between the MAPK insert and αG helix plays a major role in the substrate recognition by MKPs.	RESULTS
149	153	MKPs	protein_type	These data indicated that a unique hydrophobic pocket formed between the MAPK insert and αG helix plays a major role in the substrate recognition by MKPs.	RESULTS
0	6	F-site	site	F-site interaction is crucial for JNK1 inactivation in vivo	RESULTS
34	38	JNK1	protein	F-site interaction is crucial for JNK1 inactivation in vivo	RESULTS
0	3	JNK	protein_type	JNK is activated following cellular exposure to a number of acute stimuli such as anisomycin, H2O2, ultraviolet light, sorbitol, DNA-damaging agents and several strong apoptosis inducers (etoposide, cisplatin and taxol).	RESULTS
82	92	anisomycin	chemical	JNK is activated following cellular exposure to a number of acute stimuli such as anisomycin, H2O2, ultraviolet light, sorbitol, DNA-damaging agents and several strong apoptosis inducers (etoposide, cisplatin and taxol).	RESULTS
94	98	H2O2	chemical	JNK is activated following cellular exposure to a number of acute stimuli such as anisomycin, H2O2, ultraviolet light, sorbitol, DNA-damaging agents and several strong apoptosis inducers (etoposide, cisplatin and taxol).	RESULTS
119	127	sorbitol	chemical	JNK is activated following cellular exposure to a number of acute stimuli such as anisomycin, H2O2, ultraviolet light, sorbitol, DNA-damaging agents and several strong apoptosis inducers (etoposide, cisplatin and taxol).	RESULTS
188	197	etoposide	chemical	JNK is activated following cellular exposure to a number of acute stimuli such as anisomycin, H2O2, ultraviolet light, sorbitol, DNA-damaging agents and several strong apoptosis inducers (etoposide, cisplatin and taxol).	RESULTS
199	208	cisplatin	chemical	JNK is activated following cellular exposure to a number of acute stimuli such as anisomycin, H2O2, ultraviolet light, sorbitol, DNA-damaging agents and several strong apoptosis inducers (etoposide, cisplatin and taxol).	RESULTS
213	218	taxol	chemical	JNK is activated following cellular exposure to a number of acute stimuli such as anisomycin, H2O2, ultraviolet light, sorbitol, DNA-damaging agents and several strong apoptosis inducers (etoposide, cisplatin and taxol).	RESULTS
25	29	MKP7	protein	To assess the effects of MKP7 and its mutants on the activation of endogenous JNK in vivo, HEK293T cells were transfected with blank vector or with HA-tagged constructs for full-length MKP7, MKP7ΔC304 and MKP7-CD or MKP7 mutants, and stimulated with ultraviolet or etoposide treatment.	RESULTS
38	45	mutants	protein_state	To assess the effects of MKP7 and its mutants on the activation of endogenous JNK in vivo, HEK293T cells were transfected with blank vector or with HA-tagged constructs for full-length MKP7, MKP7ΔC304 and MKP7-CD or MKP7 mutants, and stimulated with ultraviolet or etoposide treatment.	RESULTS
78	81	JNK	protein_type	To assess the effects of MKP7 and its mutants on the activation of endogenous JNK in vivo, HEK293T cells were transfected with blank vector or with HA-tagged constructs for full-length MKP7, MKP7ΔC304 and MKP7-CD or MKP7 mutants, and stimulated with ultraviolet or etoposide treatment.	RESULTS
148	157	HA-tagged	protein_state	To assess the effects of MKP7 and its mutants on the activation of endogenous JNK in vivo, HEK293T cells were transfected with blank vector or with HA-tagged constructs for full-length MKP7, MKP7ΔC304 and MKP7-CD or MKP7 mutants, and stimulated with ultraviolet or etoposide treatment.	RESULTS
173	184	full-length	protein_state	To assess the effects of MKP7 and its mutants on the activation of endogenous JNK in vivo, HEK293T cells were transfected with blank vector or with HA-tagged constructs for full-length MKP7, MKP7ΔC304 and MKP7-CD or MKP7 mutants, and stimulated with ultraviolet or etoposide treatment.	RESULTS
185	189	MKP7	protein	To assess the effects of MKP7 and its mutants on the activation of endogenous JNK in vivo, HEK293T cells were transfected with blank vector or with HA-tagged constructs for full-length MKP7, MKP7ΔC304 and MKP7-CD or MKP7 mutants, and stimulated with ultraviolet or etoposide treatment.	RESULTS
191	200	MKP7ΔC304	mutant	To assess the effects of MKP7 and its mutants on the activation of endogenous JNK in vivo, HEK293T cells were transfected with blank vector or with HA-tagged constructs for full-length MKP7, MKP7ΔC304 and MKP7-CD or MKP7 mutants, and stimulated with ultraviolet or etoposide treatment.	RESULTS
205	209	MKP7	protein	To assess the effects of MKP7 and its mutants on the activation of endogenous JNK in vivo, HEK293T cells were transfected with blank vector or with HA-tagged constructs for full-length MKP7, MKP7ΔC304 and MKP7-CD or MKP7 mutants, and stimulated with ultraviolet or etoposide treatment.	RESULTS
210	212	CD	structure_element	To assess the effects of MKP7 and its mutants on the activation of endogenous JNK in vivo, HEK293T cells were transfected with blank vector or with HA-tagged constructs for full-length MKP7, MKP7ΔC304 and MKP7-CD or MKP7 mutants, and stimulated with ultraviolet or etoposide treatment.	RESULTS
216	220	MKP7	protein	To assess the effects of MKP7 and its mutants on the activation of endogenous JNK in vivo, HEK293T cells were transfected with blank vector or with HA-tagged constructs for full-length MKP7, MKP7ΔC304 and MKP7-CD or MKP7 mutants, and stimulated with ultraviolet or etoposide treatment.	RESULTS
221	228	mutants	protein_state	To assess the effects of MKP7 and its mutants on the activation of endogenous JNK in vivo, HEK293T cells were transfected with blank vector or with HA-tagged constructs for full-length MKP7, MKP7ΔC304 and MKP7-CD or MKP7 mutants, and stimulated with ultraviolet or etoposide treatment.	RESULTS
265	274	etoposide	chemical	To assess the effects of MKP7 and its mutants on the activation of endogenous JNK in vivo, HEK293T cells were transfected with blank vector or with HA-tagged constructs for full-length MKP7, MKP7ΔC304 and MKP7-CD or MKP7 mutants, and stimulated with ultraviolet or etoposide treatment.	RESULTS
23	36	immunobloting	experimental_method	As shown in Fig. 6a–c, immunobloting showed similar expression levels for the different MKP7 constructs in all the cells.	RESULTS
88	92	MKP7	protein	As shown in Fig. 6a–c, immunobloting showed similar expression levels for the different MKP7 constructs in all the cells.	RESULTS
0	13	Overexpressed	experimental_method	Overexpressed full-length MKP7, MKP7ΔC304 and MKP7-CD significantly reduced the endogenous level of phosphorylated JNK compared with vector-transfected cells.	RESULTS
14	25	full-length	protein_state	Overexpressed full-length MKP7, MKP7ΔC304 and MKP7-CD significantly reduced the endogenous level of phosphorylated JNK compared with vector-transfected cells.	RESULTS
26	30	MKP7	protein	Overexpressed full-length MKP7, MKP7ΔC304 and MKP7-CD significantly reduced the endogenous level of phosphorylated JNK compared with vector-transfected cells.	RESULTS
32	41	MKP7ΔC304	mutant	Overexpressed full-length MKP7, MKP7ΔC304 and MKP7-CD significantly reduced the endogenous level of phosphorylated JNK compared with vector-transfected cells.	RESULTS
46	50	MKP7	protein	Overexpressed full-length MKP7, MKP7ΔC304 and MKP7-CD significantly reduced the endogenous level of phosphorylated JNK compared with vector-transfected cells.	RESULTS
51	53	CD	structure_element	Overexpressed full-length MKP7, MKP7ΔC304 and MKP7-CD significantly reduced the endogenous level of phosphorylated JNK compared with vector-transfected cells.	RESULTS
100	114	phosphorylated	protein_state	Overexpressed full-length MKP7, MKP7ΔC304 and MKP7-CD significantly reduced the endogenous level of phosphorylated JNK compared with vector-transfected cells.	RESULTS
115	118	JNK	protein_type	Overexpressed full-length MKP7, MKP7ΔC304 and MKP7-CD significantly reduced the endogenous level of phosphorylated JNK compared with vector-transfected cells.	RESULTS
45	52	D-motif	structure_element	Parallel experiments showed clearly that the D-motif mutants (R56A/R57A and V63A/I65A) dephosphorylated JNK as did the wild type under the same conditions, further confirming that the MKP7-KBD is not required for the JNK inactivation in vivo.	RESULTS
53	60	mutants	protein_state	Parallel experiments showed clearly that the D-motif mutants (R56A/R57A and V63A/I65A) dephosphorylated JNK as did the wild type under the same conditions, further confirming that the MKP7-KBD is not required for the JNK inactivation in vivo.	RESULTS
62	66	R56A	mutant	Parallel experiments showed clearly that the D-motif mutants (R56A/R57A and V63A/I65A) dephosphorylated JNK as did the wild type under the same conditions, further confirming that the MKP7-KBD is not required for the JNK inactivation in vivo.	RESULTS
67	71	R57A	mutant	Parallel experiments showed clearly that the D-motif mutants (R56A/R57A and V63A/I65A) dephosphorylated JNK as did the wild type under the same conditions, further confirming that the MKP7-KBD is not required for the JNK inactivation in vivo.	RESULTS
76	80	V63A	mutant	Parallel experiments showed clearly that the D-motif mutants (R56A/R57A and V63A/I65A) dephosphorylated JNK as did the wild type under the same conditions, further confirming that the MKP7-KBD is not required for the JNK inactivation in vivo.	RESULTS
81	85	I65A	mutant	Parallel experiments showed clearly that the D-motif mutants (R56A/R57A and V63A/I65A) dephosphorylated JNK as did the wild type under the same conditions, further confirming that the MKP7-KBD is not required for the JNK inactivation in vivo.	RESULTS
87	103	dephosphorylated	protein_state	Parallel experiments showed clearly that the D-motif mutants (R56A/R57A and V63A/I65A) dephosphorylated JNK as did the wild type under the same conditions, further confirming that the MKP7-KBD is not required for the JNK inactivation in vivo.	RESULTS
104	107	JNK	protein_type	Parallel experiments showed clearly that the D-motif mutants (R56A/R57A and V63A/I65A) dephosphorylated JNK as did the wild type under the same conditions, further confirming that the MKP7-KBD is not required for the JNK inactivation in vivo.	RESULTS
119	128	wild type	protein_state	Parallel experiments showed clearly that the D-motif mutants (R56A/R57A and V63A/I65A) dephosphorylated JNK as did the wild type under the same conditions, further confirming that the MKP7-KBD is not required for the JNK inactivation in vivo.	RESULTS
184	188	MKP7	protein	Parallel experiments showed clearly that the D-motif mutants (R56A/R57A and V63A/I65A) dephosphorylated JNK as did the wild type under the same conditions, further confirming that the MKP7-KBD is not required for the JNK inactivation in vivo.	RESULTS
189	192	KBD	structure_element	Parallel experiments showed clearly that the D-motif mutants (R56A/R57A and V63A/I65A) dephosphorylated JNK as did the wild type under the same conditions, further confirming that the MKP7-KBD is not required for the JNK inactivation in vivo.	RESULTS
217	220	JNK	protein_type	Parallel experiments showed clearly that the D-motif mutants (R56A/R57A and V63A/I65A) dephosphorylated JNK as did the wild type under the same conditions, further confirming that the MKP7-KBD is not required for the JNK inactivation in vivo.	RESULTS
48	62	phosphorylated	protein_state	Consistent with the in vitro data, the level of phosphorylated JNK was not or little altered in MKP7 FXF-motif mutants (F285D, F287D and L288D)-transfected cells, and the MKP7 D268A and N286A mutants retained the ability to reduce the phosphorylation levels of JNK.	RESULTS
63	66	JNK	protein_type	Consistent with the in vitro data, the level of phosphorylated JNK was not or little altered in MKP7 FXF-motif mutants (F285D, F287D and L288D)-transfected cells, and the MKP7 D268A and N286A mutants retained the ability to reduce the phosphorylation levels of JNK.	RESULTS
96	100	MKP7	protein	Consistent with the in vitro data, the level of phosphorylated JNK was not or little altered in MKP7 FXF-motif mutants (F285D, F287D and L288D)-transfected cells, and the MKP7 D268A and N286A mutants retained the ability to reduce the phosphorylation levels of JNK.	RESULTS
101	110	FXF-motif	structure_element	Consistent with the in vitro data, the level of phosphorylated JNK was not or little altered in MKP7 FXF-motif mutants (F285D, F287D and L288D)-transfected cells, and the MKP7 D268A and N286A mutants retained the ability to reduce the phosphorylation levels of JNK.	RESULTS
111	118	mutants	protein_state	Consistent with the in vitro data, the level of phosphorylated JNK was not or little altered in MKP7 FXF-motif mutants (F285D, F287D and L288D)-transfected cells, and the MKP7 D268A and N286A mutants retained the ability to reduce the phosphorylation levels of JNK.	RESULTS
120	125	F285D	mutant	Consistent with the in vitro data, the level of phosphorylated JNK was not or little altered in MKP7 FXF-motif mutants (F285D, F287D and L288D)-transfected cells, and the MKP7 D268A and N286A mutants retained the ability to reduce the phosphorylation levels of JNK.	RESULTS
127	132	F287D	mutant	Consistent with the in vitro data, the level of phosphorylated JNK was not or little altered in MKP7 FXF-motif mutants (F285D, F287D and L288D)-transfected cells, and the MKP7 D268A and N286A mutants retained the ability to reduce the phosphorylation levels of JNK.	RESULTS
137	142	L288D	mutant	Consistent with the in vitro data, the level of phosphorylated JNK was not or little altered in MKP7 FXF-motif mutants (F285D, F287D and L288D)-transfected cells, and the MKP7 D268A and N286A mutants retained the ability to reduce the phosphorylation levels of JNK.	RESULTS
171	175	MKP7	protein	Consistent with the in vitro data, the level of phosphorylated JNK was not or little altered in MKP7 FXF-motif mutants (F285D, F287D and L288D)-transfected cells, and the MKP7 D268A and N286A mutants retained the ability to reduce the phosphorylation levels of JNK.	RESULTS
176	181	D268A	mutant	Consistent with the in vitro data, the level of phosphorylated JNK was not or little altered in MKP7 FXF-motif mutants (F285D, F287D and L288D)-transfected cells, and the MKP7 D268A and N286A mutants retained the ability to reduce the phosphorylation levels of JNK.	RESULTS
186	191	N286A	mutant	Consistent with the in vitro data, the level of phosphorylated JNK was not or little altered in MKP7 FXF-motif mutants (F285D, F287D and L288D)-transfected cells, and the MKP7 D268A and N286A mutants retained the ability to reduce the phosphorylation levels of JNK.	RESULTS
192	199	mutants	protein_state	Consistent with the in vitro data, the level of phosphorylated JNK was not or little altered in MKP7 FXF-motif mutants (F285D, F287D and L288D)-transfected cells, and the MKP7 D268A and N286A mutants retained the ability to reduce the phosphorylation levels of JNK.	RESULTS
261	264	JNK	protein_type	Consistent with the in vitro data, the level of phosphorylated JNK was not or little altered in MKP7 FXF-motif mutants (F285D, F287D and L288D)-transfected cells, and the MKP7 D268A and N286A mutants retained the ability to reduce the phosphorylation levels of JNK.	RESULTS
44	48	JNK1	protein	We next tested in vivo interactions between JNK1 mutants and full-length MKP7 by coimmunoprecipitation experiments under unstimulated conditions.	RESULTS
49	56	mutants	protein_state	We next tested in vivo interactions between JNK1 mutants and full-length MKP7 by coimmunoprecipitation experiments under unstimulated conditions.	RESULTS
61	72	full-length	protein_state	We next tested in vivo interactions between JNK1 mutants and full-length MKP7 by coimmunoprecipitation experiments under unstimulated conditions.	RESULTS
73	77	MKP7	protein	We next tested in vivo interactions between JNK1 mutants and full-length MKP7 by coimmunoprecipitation experiments under unstimulated conditions.	RESULTS
81	114	coimmunoprecipitation experiments	experimental_method	We next tested in vivo interactions between JNK1 mutants and full-length MKP7 by coimmunoprecipitation experiments under unstimulated conditions.	RESULTS
5	17	co-expressed	experimental_method	When co-expressed in HEK293T cells, wild-type (HA)-JNK1 was readily precipitated with (Myc)-MKP7 (Fig. 6d), indicating that MKP7 binds dephosphorylated JNK1 protein in vivo.	RESULTS
36	45	wild-type	protein_state	When co-expressed in HEK293T cells, wild-type (HA)-JNK1 was readily precipitated with (Myc)-MKP7 (Fig. 6d), indicating that MKP7 binds dephosphorylated JNK1 protein in vivo.	RESULTS
51	55	JNK1	protein	When co-expressed in HEK293T cells, wild-type (HA)-JNK1 was readily precipitated with (Myc)-MKP7 (Fig. 6d), indicating that MKP7 binds dephosphorylated JNK1 protein in vivo.	RESULTS
92	96	MKP7	protein	When co-expressed in HEK293T cells, wild-type (HA)-JNK1 was readily precipitated with (Myc)-MKP7 (Fig. 6d), indicating that MKP7 binds dephosphorylated JNK1 protein in vivo.	RESULTS
124	128	MKP7	protein	When co-expressed in HEK293T cells, wild-type (HA)-JNK1 was readily precipitated with (Myc)-MKP7 (Fig. 6d), indicating that MKP7 binds dephosphorylated JNK1 protein in vivo.	RESULTS
135	151	dephosphorylated	protein_state	When co-expressed in HEK293T cells, wild-type (HA)-JNK1 was readily precipitated with (Myc)-MKP7 (Fig. 6d), indicating that MKP7 binds dephosphorylated JNK1 protein in vivo.	RESULTS
152	156	JNK1	protein	When co-expressed in HEK293T cells, wild-type (HA)-JNK1 was readily precipitated with (Myc)-MKP7 (Fig. 6d), indicating that MKP7 binds dephosphorylated JNK1 protein in vivo.	RESULTS
22	40	in vitro pull-down	experimental_method	In agreement with the in vitro pull-down results, the mutants D229A, W234D and Y259D were not co-precipitated with MKP7, and the I231D mutant had only little effect on the JNK1–MKP7 interaction (Fig. 6d and Supplementary Fig. 3a).	RESULTS
54	61	mutants	protein_state	In agreement with the in vitro pull-down results, the mutants D229A, W234D and Y259D were not co-precipitated with MKP7, and the I231D mutant had only little effect on the JNK1–MKP7 interaction (Fig. 6d and Supplementary Fig. 3a).	RESULTS
62	67	D229A	mutant	In agreement with the in vitro pull-down results, the mutants D229A, W234D and Y259D were not co-precipitated with MKP7, and the I231D mutant had only little effect on the JNK1–MKP7 interaction (Fig. 6d and Supplementary Fig. 3a).	RESULTS
69	74	W234D	mutant	In agreement with the in vitro pull-down results, the mutants D229A, W234D and Y259D were not co-precipitated with MKP7, and the I231D mutant had only little effect on the JNK1–MKP7 interaction (Fig. 6d and Supplementary Fig. 3a).	RESULTS
79	84	Y259D	mutant	In agreement with the in vitro pull-down results, the mutants D229A, W234D and Y259D were not co-precipitated with MKP7, and the I231D mutant had only little effect on the JNK1–MKP7 interaction (Fig. 6d and Supplementary Fig. 3a).	RESULTS
115	119	MKP7	protein	In agreement with the in vitro pull-down results, the mutants D229A, W234D and Y259D were not co-precipitated with MKP7, and the I231D mutant had only little effect on the JNK1–MKP7 interaction (Fig. 6d and Supplementary Fig. 3a).	RESULTS
129	134	I231D	mutant	In agreement with the in vitro pull-down results, the mutants D229A, W234D and Y259D were not co-precipitated with MKP7, and the I231D mutant had only little effect on the JNK1–MKP7 interaction (Fig. 6d and Supplementary Fig. 3a).	RESULTS
135	141	mutant	protein_state	In agreement with the in vitro pull-down results, the mutants D229A, W234D and Y259D were not co-precipitated with MKP7, and the I231D mutant had only little effect on the JNK1–MKP7 interaction (Fig. 6d and Supplementary Fig. 3a).	RESULTS
172	181	JNK1–MKP7	complex_assembly	In agreement with the in vitro pull-down results, the mutants D229A, W234D and Y259D were not co-precipitated with MKP7, and the I231D mutant had only little effect on the JNK1–MKP7 interaction (Fig. 6d and Supplementary Fig. 3a).	RESULTS
18	21	JNK	protein_type	Activation of the JNK signalling pathway is frequently associated with apoptotic cell death, and inhibition of JNK can prevent apoptotic death of multiple cells.	RESULTS
111	114	JNK	protein_type	Activation of the JNK signalling pathway is frequently associated with apoptotic cell death, and inhibition of JNK can prevent apoptotic death of multiple cells.	RESULTS
37	40	JNK	protein_type	To examine whether the inhibition of JNK activity by MKP7 would provide protections against the apoptosis, we analysed the rate of apoptosis in ultraviolet-irradiated cells transfected with MKP7 (wild type or mutants) by flow cytometry.	RESULTS
53	57	MKP7	protein	To examine whether the inhibition of JNK activity by MKP7 would provide protections against the apoptosis, we analysed the rate of apoptosis in ultraviolet-irradiated cells transfected with MKP7 (wild type or mutants) by flow cytometry.	RESULTS
190	194	MKP7	protein	To examine whether the inhibition of JNK activity by MKP7 would provide protections against the apoptosis, we analysed the rate of apoptosis in ultraviolet-irradiated cells transfected with MKP7 (wild type or mutants) by flow cytometry.	RESULTS
196	205	wild type	protein_state	To examine whether the inhibition of JNK activity by MKP7 would provide protections against the apoptosis, we analysed the rate of apoptosis in ultraviolet-irradiated cells transfected with MKP7 (wild type or mutants) by flow cytometry.	RESULTS
209	216	mutants	protein_state	To examine whether the inhibition of JNK activity by MKP7 would provide protections against the apoptosis, we analysed the rate of apoptosis in ultraviolet-irradiated cells transfected with MKP7 (wild type or mutants) by flow cytometry.	RESULTS
221	235	flow cytometry	experimental_method	To examine whether the inhibition of JNK activity by MKP7 would provide protections against the apoptosis, we analysed the rate of apoptosis in ultraviolet-irradiated cells transfected with MKP7 (wild type or mutants) by flow cytometry.	RESULTS
95	99	MKP7	protein	The results showed similar apoptotic rates between cells transfected with blank vector or with MKP7 (wild type or mutants) under unstimulated conditions (Supplementary Fig. 3b), while ultraviolet-irradiation significantly increased apoptotic rate in cells transfected with blank vector (Fig. 6e).	RESULTS
101	110	wild type	protein_state	The results showed similar apoptotic rates between cells transfected with blank vector or with MKP7 (wild type or mutants) under unstimulated conditions (Supplementary Fig. 3b), while ultraviolet-irradiation significantly increased apoptotic rate in cells transfected with blank vector (Fig. 6e).	RESULTS
114	121	mutants	protein_state	The results showed similar apoptotic rates between cells transfected with blank vector or with MKP7 (wild type or mutants) under unstimulated conditions (Supplementary Fig. 3b), while ultraviolet-irradiation significantly increased apoptotic rate in cells transfected with blank vector (Fig. 6e).	RESULTS
0	11	Expressions	experimental_method	Expressions of wild-type MKP7, MKP7ΔC304 and MKP7-CD significantly decreased the proportion of apoptotic cells after ultraviolet treatment.	RESULTS
15	24	wild-type	protein_state	Expressions of wild-type MKP7, MKP7ΔC304 and MKP7-CD significantly decreased the proportion of apoptotic cells after ultraviolet treatment.	RESULTS
25	29	MKP7	protein	Expressions of wild-type MKP7, MKP7ΔC304 and MKP7-CD significantly decreased the proportion of apoptotic cells after ultraviolet treatment.	RESULTS
31	40	MKP7ΔC304	mutant	Expressions of wild-type MKP7, MKP7ΔC304 and MKP7-CD significantly decreased the proportion of apoptotic cells after ultraviolet treatment.	RESULTS
45	49	MKP7	protein	Expressions of wild-type MKP7, MKP7ΔC304 and MKP7-CD significantly decreased the proportion of apoptotic cells after ultraviolet treatment.	RESULTS
50	52	CD	structure_element	Expressions of wild-type MKP7, MKP7ΔC304 and MKP7-CD significantly decreased the proportion of apoptotic cells after ultraviolet treatment.	RESULTS
40	44	MKP7	protein	Moreover, treatment of cells expressing MKP7-KBD mutants (R56A/R57A and V63A/I65A) decreased the apoptosis rates to a similar extent as MKP7 wild type did.	RESULTS
45	48	KBD	structure_element	Moreover, treatment of cells expressing MKP7-KBD mutants (R56A/R57A and V63A/I65A) decreased the apoptosis rates to a similar extent as MKP7 wild type did.	RESULTS
49	56	mutants	protein_state	Moreover, treatment of cells expressing MKP7-KBD mutants (R56A/R57A and V63A/I65A) decreased the apoptosis rates to a similar extent as MKP7 wild type did.	RESULTS
58	62	R56A	mutant	Moreover, treatment of cells expressing MKP7-KBD mutants (R56A/R57A and V63A/I65A) decreased the apoptosis rates to a similar extent as MKP7 wild type did.	RESULTS
63	67	R57A	mutant	Moreover, treatment of cells expressing MKP7-KBD mutants (R56A/R57A and V63A/I65A) decreased the apoptosis rates to a similar extent as MKP7 wild type did.	RESULTS
72	76	V63A	mutant	Moreover, treatment of cells expressing MKP7-KBD mutants (R56A/R57A and V63A/I65A) decreased the apoptosis rates to a similar extent as MKP7 wild type did.	RESULTS
77	81	I65A	mutant	Moreover, treatment of cells expressing MKP7-KBD mutants (R56A/R57A and V63A/I65A) decreased the apoptosis rates to a similar extent as MKP7 wild type did.	RESULTS
136	140	MKP7	protein	Moreover, treatment of cells expressing MKP7-KBD mutants (R56A/R57A and V63A/I65A) decreased the apoptosis rates to a similar extent as MKP7 wild type did.	RESULTS
141	150	wild type	protein_state	Moreover, treatment of cells expressing MKP7-KBD mutants (R56A/R57A and V63A/I65A) decreased the apoptosis rates to a similar extent as MKP7 wild type did.	RESULTS
40	44	MKP7	protein	In contrast, cells transfected with the MKP7 FXF-motif mutants (F285D, F287D and L288D) showed little protective effect after ultraviolet treatment and similar levels of apoptosis rates were detected to cells transfected with control vectors (Fig. 6e,f).	RESULTS
45	54	FXF-motif	structure_element	In contrast, cells transfected with the MKP7 FXF-motif mutants (F285D, F287D and L288D) showed little protective effect after ultraviolet treatment and similar levels of apoptosis rates were detected to cells transfected with control vectors (Fig. 6e,f).	RESULTS
55	62	mutants	protein_state	In contrast, cells transfected with the MKP7 FXF-motif mutants (F285D, F287D and L288D) showed little protective effect after ultraviolet treatment and similar levels of apoptosis rates were detected to cells transfected with control vectors (Fig. 6e,f).	RESULTS
64	69	F285D	mutant	In contrast, cells transfected with the MKP7 FXF-motif mutants (F285D, F287D and L288D) showed little protective effect after ultraviolet treatment and similar levels of apoptosis rates were detected to cells transfected with control vectors (Fig. 6e,f).	RESULTS
71	76	F287D	mutant	In contrast, cells transfected with the MKP7 FXF-motif mutants (F285D, F287D and L288D) showed little protective effect after ultraviolet treatment and similar levels of apoptosis rates were detected to cells transfected with control vectors (Fig. 6e,f).	RESULTS
81	86	L288D	mutant	In contrast, cells transfected with the MKP7 FXF-motif mutants (F285D, F287D and L288D) showed little protective effect after ultraviolet treatment and similar levels of apoptosis rates were detected to cells transfected with control vectors (Fig. 6e,f).	RESULTS
43	52	FXF-motif	structure_element	Taken together, our results suggested that FXF-motif-mediated, rather than KBD-mediated, interaction is essential for MKP7 to block ultraviolet-induced apoptosis.	RESULTS
75	78	KBD	structure_element	Taken together, our results suggested that FXF-motif-mediated, rather than KBD-mediated, interaction is essential for MKP7 to block ultraviolet-induced apoptosis.	RESULTS
118	122	MKP7	protein	Taken together, our results suggested that FXF-motif-mediated, rather than KBD-mediated, interaction is essential for MKP7 to block ultraviolet-induced apoptosis.	RESULTS
32	36	JNK1	protein	A similar docking mechanism for JNK1 recognition by MKP5	RESULTS
52	56	MKP5	protein	A similar docking mechanism for JNK1 recognition by MKP5	RESULTS
0	4	MKP5	protein	MKP5 belongs to the same subfamily as MKP7.	RESULTS
38	42	MKP7	protein	MKP5 belongs to the same subfamily as MKP7.	RESULTS
0	4	MKP5	protein	MKP5 is unique among the MKPs in possessing an additional domain of unknown function at the N-terminus (Fig. 7a).	RESULTS
25	29	MKPs	protein_type	MKP5 is unique among the MKPs in possessing an additional domain of unknown function at the N-terminus (Fig. 7a).	RESULTS
4	7	KBD	structure_element	The KBD of MKP5 interacts with the D-site of p38α to mediate the enzyme–substrate interaction.	RESULTS
11	15	MKP5	protein	The KBD of MKP5 interacts with the D-site of p38α to mediate the enzyme–substrate interaction.	RESULTS
35	41	D-site	site	The KBD of MKP5 interacts with the D-site of p38α to mediate the enzyme–substrate interaction.	RESULTS
45	49	p38α	protein	The KBD of MKP5 interacts with the D-site of p38α to mediate the enzyme–substrate interaction.	RESULTS
0	11	Deletion of	experimental_method	Deletion of the KBD in MKP5 leads to a 280-fold increase in Km for p38α substrate.	RESULTS
16	19	KBD	structure_element	Deletion of the KBD in MKP5 leads to a 280-fold increase in Km for p38α substrate.	RESULTS
23	27	MKP5	protein	Deletion of the KBD in MKP5 leads to a 280-fold increase in Km for p38α substrate.	RESULTS
60	62	Km	evidence	Deletion of the KBD in MKP5 leads to a 280-fold increase in Km for p38α substrate.	RESULTS
67	71	p38α	protein	Deletion of the KBD in MKP5 leads to a 280-fold increase in Km for p38α substrate.	RESULTS
15	19	p38α	protein	In contrast to p38α substrate, deletion of the MKP5-KBD had little effects on the kinetic parameters for the JNK1 dephosphorylation, indicating that the KBD of MKP5 is not required for the JNK1 dephosphorylation (Fig. 7b).	RESULTS
31	42	deletion of	experimental_method	In contrast to p38α substrate, deletion of the MKP5-KBD had little effects on the kinetic parameters for the JNK1 dephosphorylation, indicating that the KBD of MKP5 is not required for the JNK1 dephosphorylation (Fig. 7b).	RESULTS
47	51	MKP5	protein	In contrast to p38α substrate, deletion of the MKP5-KBD had little effects on the kinetic parameters for the JNK1 dephosphorylation, indicating that the KBD of MKP5 is not required for the JNK1 dephosphorylation (Fig. 7b).	RESULTS
52	55	KBD	structure_element	In contrast to p38α substrate, deletion of the MKP5-KBD had little effects on the kinetic parameters for the JNK1 dephosphorylation, indicating that the KBD of MKP5 is not required for the JNK1 dephosphorylation (Fig. 7b).	RESULTS
109	113	JNK1	protein	In contrast to p38α substrate, deletion of the MKP5-KBD had little effects on the kinetic parameters for the JNK1 dephosphorylation, indicating that the KBD of MKP5 is not required for the JNK1 dephosphorylation (Fig. 7b).	RESULTS
153	156	KBD	structure_element	In contrast to p38α substrate, deletion of the MKP5-KBD had little effects on the kinetic parameters for the JNK1 dephosphorylation, indicating that the KBD of MKP5 is not required for the JNK1 dephosphorylation (Fig. 7b).	RESULTS
160	164	MKP5	protein	In contrast to p38α substrate, deletion of the MKP5-KBD had little effects on the kinetic parameters for the JNK1 dephosphorylation, indicating that the KBD of MKP5 is not required for the JNK1 dephosphorylation (Fig. 7b).	RESULTS
189	193	JNK1	protein	In contrast to p38α substrate, deletion of the MKP5-KBD had little effects on the kinetic parameters for the JNK1 dephosphorylation, indicating that the KBD of MKP5 is not required for the JNK1 dephosphorylation (Fig. 7b).	RESULTS
4	34	substrate specificity constant	evidence	The substrate specificity constant kcat /Km value for MKP5-CD was calculated as 1.0 × 105 M−1 s−1, which is very close to that of MKP7-CD (1.07 × 105 M−1 s−1).	RESULTS
35	43	kcat /Km	evidence	The substrate specificity constant kcat /Km value for MKP5-CD was calculated as 1.0 × 105 M−1 s−1, which is very close to that of MKP7-CD (1.07 × 105 M−1 s−1).	RESULTS
54	58	MKP5	protein	The substrate specificity constant kcat /Km value for MKP5-CD was calculated as 1.0 × 105 M−1 s−1, which is very close to that of MKP7-CD (1.07 × 105 M−1 s−1).	RESULTS
59	61	CD	structure_element	The substrate specificity constant kcat /Km value for MKP5-CD was calculated as 1.0 × 105 M−1 s−1, which is very close to that of MKP7-CD (1.07 × 105 M−1 s−1).	RESULTS
130	134	MKP7	protein	The substrate specificity constant kcat /Km value for MKP5-CD was calculated as 1.0 × 105 M−1 s−1, which is very close to that of MKP7-CD (1.07 × 105 M−1 s−1).	RESULTS
135	137	CD	structure_element	The substrate specificity constant kcat /Km value for MKP5-CD was calculated as 1.0 × 105 M−1 s−1, which is very close to that of MKP7-CD (1.07 × 105 M−1 s−1).	RESULTS
4	21	crystal structure	evidence	The crystal structure of human MKP5-CD has been determined.	RESULTS
25	30	human	species	The crystal structure of human MKP5-CD has been determined.	RESULTS
31	35	MKP5	protein	The crystal structure of human MKP5-CD has been determined.	RESULTS
36	38	CD	structure_element	The crystal structure of human MKP5-CD has been determined.	RESULTS
20	37	catalytic domains	structure_element	Comparisons between catalytic domains structures of MKP5 and MKP7 reveal that the overall folds of the two proteins are highly similar, with only a few regions exhibiting small deviations (r.m.s.d. of 0.79 Å; Fig. 7c).	RESULTS
38	48	structures	evidence	Comparisons between catalytic domains structures of MKP5 and MKP7 reveal that the overall folds of the two proteins are highly similar, with only a few regions exhibiting small deviations (r.m.s.d. of 0.79 Å; Fig. 7c).	RESULTS
52	56	MKP5	protein	Comparisons between catalytic domains structures of MKP5 and MKP7 reveal that the overall folds of the two proteins are highly similar, with only a few regions exhibiting small deviations (r.m.s.d. of 0.79 Å; Fig. 7c).	RESULTS
61	65	MKP7	protein	Comparisons between catalytic domains structures of MKP5 and MKP7 reveal that the overall folds of the two proteins are highly similar, with only a few regions exhibiting small deviations (r.m.s.d. of 0.79 Å; Fig. 7c).	RESULTS
189	197	r.m.s.d.	evidence	Comparisons between catalytic domains structures of MKP5 and MKP7 reveal that the overall folds of the two proteins are highly similar, with only a few regions exhibiting small deviations (r.m.s.d. of 0.79 Å; Fig. 7c).	RESULTS
52	69	crystal structure	evidence	Given the distinct interaction mode revealed by the crystal structure of JNK1–MKP7-CD, one obvious question is whether this is a general mechanism used by all members of the JNK-specific MKPs.	RESULTS
73	85	JNK1–MKP7-CD	complex_assembly	Given the distinct interaction mode revealed by the crystal structure of JNK1–MKP7-CD, one obvious question is whether this is a general mechanism used by all members of the JNK-specific MKPs.	RESULTS
174	191	JNK-specific MKPs	protein_type	Given the distinct interaction mode revealed by the crystal structure of JNK1–MKP7-CD, one obvious question is whether this is a general mechanism used by all members of the JNK-specific MKPs.	RESULTS
64	68	JNK1	protein	To address this issue, we first examined the docking ability of JNK1 to the KBD and CD of MKP5 using gel filtration analysis and pull-down assays.	RESULTS
76	79	KBD	structure_element	To address this issue, we first examined the docking ability of JNK1 to the KBD and CD of MKP5 using gel filtration analysis and pull-down assays.	RESULTS
84	86	CD	structure_element	To address this issue, we first examined the docking ability of JNK1 to the KBD and CD of MKP5 using gel filtration analysis and pull-down assays.	RESULTS
90	94	MKP5	protein	To address this issue, we first examined the docking ability of JNK1 to the KBD and CD of MKP5 using gel filtration analysis and pull-down assays.	RESULTS
101	124	gel filtration analysis	experimental_method	To address this issue, we first examined the docking ability of JNK1 to the KBD and CD of MKP5 using gel filtration analysis and pull-down assays.	RESULTS
129	145	pull-down assays	experimental_method	To address this issue, we first examined the docking ability of JNK1 to the KBD and CD of MKP5 using gel filtration analysis and pull-down assays.	RESULTS
20	46	gel filtration experiments	experimental_method	It can be seen from gel filtration experiments that JNK1 can forms a stable heterodimer with MKP5-CD in solution, but no detectable interaction was found with the KBD domain (Fig. 7d).	RESULTS
52	56	JNK1	protein	It can be seen from gel filtration experiments that JNK1 can forms a stable heterodimer with MKP5-CD in solution, but no detectable interaction was found with the KBD domain (Fig. 7d).	RESULTS
69	75	stable	protein_state	It can be seen from gel filtration experiments that JNK1 can forms a stable heterodimer with MKP5-CD in solution, but no detectable interaction was found with the KBD domain (Fig. 7d).	RESULTS
76	87	heterodimer	oligomeric_state	It can be seen from gel filtration experiments that JNK1 can forms a stable heterodimer with MKP5-CD in solution, but no detectable interaction was found with the KBD domain (Fig. 7d).	RESULTS
93	97	MKP5	protein	It can be seen from gel filtration experiments that JNK1 can forms a stable heterodimer with MKP5-CD in solution, but no detectable interaction was found with the KBD domain (Fig. 7d).	RESULTS
98	100	CD	structure_element	It can be seen from gel filtration experiments that JNK1 can forms a stable heterodimer with MKP5-CD in solution, but no detectable interaction was found with the KBD domain (Fig. 7d).	RESULTS
163	166	KBD	structure_element	It can be seen from gel filtration experiments that JNK1 can forms a stable heterodimer with MKP5-CD in solution, but no detectable interaction was found with the KBD domain (Fig. 7d).	RESULTS
0	16	Pull-down assays	experimental_method	Pull-down assays also confirmed the protein–protein interactions observed above.	RESULTS
4	20	catalytic domain	structure_element	The catalytic domain of MKP5, but not its KBD, was able to pull-down a detectable amount of JNK1 (Fig. 7e), implicating a different substrate-recognition mechanisms for p38 and JNK MAPKs.	RESULTS
24	28	MKP5	protein	The catalytic domain of MKP5, but not its KBD, was able to pull-down a detectable amount of JNK1 (Fig. 7e), implicating a different substrate-recognition mechanisms for p38 and JNK MAPKs.	RESULTS
42	45	KBD	structure_element	The catalytic domain of MKP5, but not its KBD, was able to pull-down a detectable amount of JNK1 (Fig. 7e), implicating a different substrate-recognition mechanisms for p38 and JNK MAPKs.	RESULTS
92	96	JNK1	protein	The catalytic domain of MKP5, but not its KBD, was able to pull-down a detectable amount of JNK1 (Fig. 7e), implicating a different substrate-recognition mechanisms for p38 and JNK MAPKs.	RESULTS
169	172	p38	protein_type	The catalytic domain of MKP5, but not its KBD, was able to pull-down a detectable amount of JNK1 (Fig. 7e), implicating a different substrate-recognition mechanisms for p38 and JNK MAPKs.	RESULTS
177	180	JNK	protein_type	The catalytic domain of MKP5, but not its KBD, was able to pull-down a detectable amount of JNK1 (Fig. 7e), implicating a different substrate-recognition mechanisms for p38 and JNK MAPKs.	RESULTS
181	186	MAPKs	protein_type	The catalytic domain of MKP5, but not its KBD, was able to pull-down a detectable amount of JNK1 (Fig. 7e), implicating a different substrate-recognition mechanisms for p38 and JNK MAPKs.	RESULTS
54	58	MKP5	protein	To further test our hypothesis, we generated forms of MKP5-CD bearing mutations corresponding to the changes we made on MKP7-CD on the basis of sequence and structural alignment and examined their effects on the phosphatase activity.	RESULTS
59	61	CD	structure_element	To further test our hypothesis, we generated forms of MKP5-CD bearing mutations corresponding to the changes we made on MKP7-CD on the basis of sequence and structural alignment and examined their effects on the phosphatase activity.	RESULTS
70	79	mutations	experimental_method	To further test our hypothesis, we generated forms of MKP5-CD bearing mutations corresponding to the changes we made on MKP7-CD on the basis of sequence and structural alignment and examined their effects on the phosphatase activity.	RESULTS
120	124	MKP7	protein	To further test our hypothesis, we generated forms of MKP5-CD bearing mutations corresponding to the changes we made on MKP7-CD on the basis of sequence and structural alignment and examined their effects on the phosphatase activity.	RESULTS
125	127	CD	structure_element	To further test our hypothesis, we generated forms of MKP5-CD bearing mutations corresponding to the changes we made on MKP7-CD on the basis of sequence and structural alignment and examined their effects on the phosphatase activity.	RESULTS
144	177	sequence and structural alignment	experimental_method	To further test our hypothesis, we generated forms of MKP5-CD bearing mutations corresponding to the changes we made on MKP7-CD on the basis of sequence and structural alignment and examined their effects on the phosphatase activity.	RESULTS
212	223	phosphatase	protein_type	To further test our hypothesis, we generated forms of MKP5-CD bearing mutations corresponding to the changes we made on MKP7-CD on the basis of sequence and structural alignment and examined their effects on the phosphatase activity.	RESULTS
25	30	T432A	mutant	As shown in Fig. 7f, the T432A and L449F MKP5 mutant showed little or no difference in phosphatase activity, whereas the other mutants showed reduced specific activities of MKP5.	RESULTS
35	40	L449F	mutant	As shown in Fig. 7f, the T432A and L449F MKP5 mutant showed little or no difference in phosphatase activity, whereas the other mutants showed reduced specific activities of MKP5.	RESULTS
41	45	MKP5	protein	As shown in Fig. 7f, the T432A and L449F MKP5 mutant showed little or no difference in phosphatase activity, whereas the other mutants showed reduced specific activities of MKP5.	RESULTS
46	52	mutant	protein_state	As shown in Fig. 7f, the T432A and L449F MKP5 mutant showed little or no difference in phosphatase activity, whereas the other mutants showed reduced specific activities of MKP5.	RESULTS
127	134	mutants	protein_state	As shown in Fig. 7f, the T432A and L449F MKP5 mutant showed little or no difference in phosphatase activity, whereas the other mutants showed reduced specific activities of MKP5.	RESULTS
173	177	MKP5	protein	As shown in Fig. 7f, the T432A and L449F MKP5 mutant showed little or no difference in phosphatase activity, whereas the other mutants showed reduced specific activities of MKP5.	RESULTS
18	22	MKP7	protein	As in the case of MKP7, all the mutants, except F451D/A, showed no pNPPase activity changes compared with the wild-type MKP5-CD (Fig. 7g), and the point mutations in JNK1 also reduced the binding affinity of MKP5-CD for JNK1 (Fig. 7h).	RESULTS
32	39	mutants	protein_state	As in the case of MKP7, all the mutants, except F451D/A, showed no pNPPase activity changes compared with the wild-type MKP5-CD (Fig. 7g), and the point mutations in JNK1 also reduced the binding affinity of MKP5-CD for JNK1 (Fig. 7h).	RESULTS
48	55	F451D/A	mutant	As in the case of MKP7, all the mutants, except F451D/A, showed no pNPPase activity changes compared with the wild-type MKP5-CD (Fig. 7g), and the point mutations in JNK1 also reduced the binding affinity of MKP5-CD for JNK1 (Fig. 7h).	RESULTS
67	74	pNPPase	protein_type	As in the case of MKP7, all the mutants, except F451D/A, showed no pNPPase activity changes compared with the wild-type MKP5-CD (Fig. 7g), and the point mutations in JNK1 also reduced the binding affinity of MKP5-CD for JNK1 (Fig. 7h).	RESULTS
110	119	wild-type	protein_state	As in the case of MKP7, all the mutants, except F451D/A, showed no pNPPase activity changes compared with the wild-type MKP5-CD (Fig. 7g), and the point mutations in JNK1 also reduced the binding affinity of MKP5-CD for JNK1 (Fig. 7h).	RESULTS
120	124	MKP5	protein	As in the case of MKP7, all the mutants, except F451D/A, showed no pNPPase activity changes compared with the wild-type MKP5-CD (Fig. 7g), and the point mutations in JNK1 also reduced the binding affinity of MKP5-CD for JNK1 (Fig. 7h).	RESULTS
125	127	CD	structure_element	As in the case of MKP7, all the mutants, except F451D/A, showed no pNPPase activity changes compared with the wild-type MKP5-CD (Fig. 7g), and the point mutations in JNK1 also reduced the binding affinity of MKP5-CD for JNK1 (Fig. 7h).	RESULTS
147	162	point mutations	experimental_method	As in the case of MKP7, all the mutants, except F451D/A, showed no pNPPase activity changes compared with the wild-type MKP5-CD (Fig. 7g), and the point mutations in JNK1 also reduced the binding affinity of MKP5-CD for JNK1 (Fig. 7h).	RESULTS
166	170	JNK1	protein	As in the case of MKP7, all the mutants, except F451D/A, showed no pNPPase activity changes compared with the wild-type MKP5-CD (Fig. 7g), and the point mutations in JNK1 also reduced the binding affinity of MKP5-CD for JNK1 (Fig. 7h).	RESULTS
188	204	binding affinity	evidence	As in the case of MKP7, all the mutants, except F451D/A, showed no pNPPase activity changes compared with the wild-type MKP5-CD (Fig. 7g), and the point mutations in JNK1 also reduced the binding affinity of MKP5-CD for JNK1 (Fig. 7h).	RESULTS
208	212	MKP5	protein	As in the case of MKP7, all the mutants, except F451D/A, showed no pNPPase activity changes compared with the wild-type MKP5-CD (Fig. 7g), and the point mutations in JNK1 also reduced the binding affinity of MKP5-CD for JNK1 (Fig. 7h).	RESULTS
213	215	CD	structure_element	As in the case of MKP7, all the mutants, except F451D/A, showed no pNPPase activity changes compared with the wild-type MKP5-CD (Fig. 7g), and the point mutations in JNK1 also reduced the binding affinity of MKP5-CD for JNK1 (Fig. 7h).	RESULTS
220	224	JNK1	protein	As in the case of MKP7, all the mutants, except F451D/A, showed no pNPPase activity changes compared with the wild-type MKP5-CD (Fig. 7g), and the point mutations in JNK1 also reduced the binding affinity of MKP5-CD for JNK1 (Fig. 7h).	RESULTS
58	68	CD spectra	evidence	In addition, there were no significant differences in the CD spectra between wild-type and mutant proteins, indicating that the overall structures of these mutants did not change significantly from that of wild-type MKP5 protein (Supplementary Fig. 4a).	RESULTS
77	86	wild-type	protein_state	In addition, there were no significant differences in the CD spectra between wild-type and mutant proteins, indicating that the overall structures of these mutants did not change significantly from that of wild-type MKP5 protein (Supplementary Fig. 4a).	RESULTS
91	97	mutant	protein_state	In addition, there were no significant differences in the CD spectra between wild-type and mutant proteins, indicating that the overall structures of these mutants did not change significantly from that of wild-type MKP5 protein (Supplementary Fig. 4a).	RESULTS
136	146	structures	evidence	In addition, there were no significant differences in the CD spectra between wild-type and mutant proteins, indicating that the overall structures of these mutants did not change significantly from that of wild-type MKP5 protein (Supplementary Fig. 4a).	RESULTS
156	163	mutants	protein_state	In addition, there were no significant differences in the CD spectra between wild-type and mutant proteins, indicating that the overall structures of these mutants did not change significantly from that of wild-type MKP5 protein (Supplementary Fig. 4a).	RESULTS
206	215	wild-type	protein_state	In addition, there were no significant differences in the CD spectra between wild-type and mutant proteins, indicating that the overall structures of these mutants did not change significantly from that of wild-type MKP5 protein (Supplementary Fig. 4a).	RESULTS
216	220	MKP5	protein	In addition, there were no significant differences in the CD spectra between wild-type and mutant proteins, indicating that the overall structures of these mutants did not change significantly from that of wild-type MKP5 protein (Supplementary Fig. 4a).	RESULTS
41	45	MKP5	protein	Taken together, our results suggest that MKP5 binds JNK1 in a docking mode similar to that in the JNK1–MKP7 complex, and the detailed interaction model can be generated using molecular dynamics simulation based on the structure of JNK1–MKP7-CD complex (Supplementary Fig. 4b,c).	RESULTS
52	56	JNK1	protein	Taken together, our results suggest that MKP5 binds JNK1 in a docking mode similar to that in the JNK1–MKP7 complex, and the detailed interaction model can be generated using molecular dynamics simulation based on the structure of JNK1–MKP7-CD complex (Supplementary Fig. 4b,c).	RESULTS
98	107	JNK1–MKP7	complex_assembly	Taken together, our results suggest that MKP5 binds JNK1 in a docking mode similar to that in the JNK1–MKP7 complex, and the detailed interaction model can be generated using molecular dynamics simulation based on the structure of JNK1–MKP7-CD complex (Supplementary Fig. 4b,c).	RESULTS
175	204	molecular dynamics simulation	experimental_method	Taken together, our results suggest that MKP5 binds JNK1 in a docking mode similar to that in the JNK1–MKP7 complex, and the detailed interaction model can be generated using molecular dynamics simulation based on the structure of JNK1–MKP7-CD complex (Supplementary Fig. 4b,c).	RESULTS
218	227	structure	evidence	Taken together, our results suggest that MKP5 binds JNK1 in a docking mode similar to that in the JNK1–MKP7 complex, and the detailed interaction model can be generated using molecular dynamics simulation based on the structure of JNK1–MKP7-CD complex (Supplementary Fig. 4b,c).	RESULTS
231	243	JNK1–MKP7-CD	complex_assembly	Taken together, our results suggest that MKP5 binds JNK1 in a docking mode similar to that in the JNK1–MKP7 complex, and the detailed interaction model can be generated using molecular dynamics simulation based on the structure of JNK1–MKP7-CD complex (Supplementary Fig. 4b,c).	RESULTS
19	23	MKP5	protein	In this model, the MKP5-CD adopts a conformation nearly identical to that in its unbound form, suggesting that the conformation of the catalytic domain undergoes little change, if any at all, upon JNK1 binding.	RESULTS
24	26	CD	structure_element	In this model, the MKP5-CD adopts a conformation nearly identical to that in its unbound form, suggesting that the conformation of the catalytic domain undergoes little change, if any at all, upon JNK1 binding.	RESULTS
81	88	unbound	protein_state	In this model, the MKP5-CD adopts a conformation nearly identical to that in its unbound form, suggesting that the conformation of the catalytic domain undergoes little change, if any at all, upon JNK1 binding.	RESULTS
135	151	catalytic domain	structure_element	In this model, the MKP5-CD adopts a conformation nearly identical to that in its unbound form, suggesting that the conformation of the catalytic domain undergoes little change, if any at all, upon JNK1 binding.	RESULTS
197	201	JNK1	protein	In this model, the MKP5-CD adopts a conformation nearly identical to that in its unbound form, suggesting that the conformation of the catalytic domain undergoes little change, if any at all, upon JNK1 binding.	RESULTS
15	21	Leu449	residue_name_number	In particular, Leu449 of MKP5, which is equivalent to the key residue Phe285 of MKP7, buried deeply within the hydrophobic pocket of JNK1 in the same way as Phe285 in the JNK1–MKP7-CD complex (Supplementary Fig. 4d).	RESULTS
25	29	MKP5	protein	In particular, Leu449 of MKP5, which is equivalent to the key residue Phe285 of MKP7, buried deeply within the hydrophobic pocket of JNK1 in the same way as Phe285 in the JNK1–MKP7-CD complex (Supplementary Fig. 4d).	RESULTS
70	76	Phe285	residue_name_number	In particular, Leu449 of MKP5, which is equivalent to the key residue Phe285 of MKP7, buried deeply within the hydrophobic pocket of JNK1 in the same way as Phe285 in the JNK1–MKP7-CD complex (Supplementary Fig. 4d).	RESULTS
80	84	MKP7	protein	In particular, Leu449 of MKP5, which is equivalent to the key residue Phe285 of MKP7, buried deeply within the hydrophobic pocket of JNK1 in the same way as Phe285 in the JNK1–MKP7-CD complex (Supplementary Fig. 4d).	RESULTS
111	129	hydrophobic pocket	site	In particular, Leu449 of MKP5, which is equivalent to the key residue Phe285 of MKP7, buried deeply within the hydrophobic pocket of JNK1 in the same way as Phe285 in the JNK1–MKP7-CD complex (Supplementary Fig. 4d).	RESULTS
133	137	JNK1	protein	In particular, Leu449 of MKP5, which is equivalent to the key residue Phe285 of MKP7, buried deeply within the hydrophobic pocket of JNK1 in the same way as Phe285 in the JNK1–MKP7-CD complex (Supplementary Fig. 4d).	RESULTS
157	163	Phe285	residue_name_number	In particular, Leu449 of MKP5, which is equivalent to the key residue Phe285 of MKP7, buried deeply within the hydrophobic pocket of JNK1 in the same way as Phe285 in the JNK1–MKP7-CD complex (Supplementary Fig. 4d).	RESULTS
171	183	JNK1–MKP7-CD	complex_assembly	In particular, Leu449 of MKP5, which is equivalent to the key residue Phe285 of MKP7, buried deeply within the hydrophobic pocket of JNK1 in the same way as Phe285 in the JNK1–MKP7-CD complex (Supplementary Fig. 4d).	RESULTS
40	44	JNK1	protein	Despite the strong similarities between JNK1–MKP5-CD and JNK1–MKP7-CD, however, there are differences.	RESULTS
45	49	MKP5	protein	Despite the strong similarities between JNK1–MKP5-CD and JNK1–MKP7-CD, however, there are differences.	RESULTS
50	52	CD	structure_element	Despite the strong similarities between JNK1–MKP5-CD and JNK1–MKP7-CD, however, there are differences.	RESULTS
57	69	JNK1–MKP7-CD	complex_assembly	Despite the strong similarities between JNK1–MKP5-CD and JNK1–MKP7-CD, however, there are differences.	RESULTS
4	16	JNK1–MKP7-CD	complex_assembly	The JNK1–MKP7-CD interaction is better and more extensive.	RESULTS
0	6	Asp268	residue_name_number	Asp268 of MKP7-CD forms salt bridge with JNK1 Arg263, whereas the corresponding residue Thr432 in MKP5-CD may not interact with JNK1.	RESULTS
10	14	MKP7	protein	Asp268 of MKP7-CD forms salt bridge with JNK1 Arg263, whereas the corresponding residue Thr432 in MKP5-CD may not interact with JNK1.	RESULTS
15	17	CD	structure_element	Asp268 of MKP7-CD forms salt bridge with JNK1 Arg263, whereas the corresponding residue Thr432 in MKP5-CD may not interact with JNK1.	RESULTS
24	35	salt bridge	bond_interaction	Asp268 of MKP7-CD forms salt bridge with JNK1 Arg263, whereas the corresponding residue Thr432 in MKP5-CD may not interact with JNK1.	RESULTS
41	45	JNK1	protein	Asp268 of MKP7-CD forms salt bridge with JNK1 Arg263, whereas the corresponding residue Thr432 in MKP5-CD may not interact with JNK1.	RESULTS
46	52	Arg263	residue_name_number	Asp268 of MKP7-CD forms salt bridge with JNK1 Arg263, whereas the corresponding residue Thr432 in MKP5-CD may not interact with JNK1.	RESULTS
88	94	Thr432	residue_name_number	Asp268 of MKP7-CD forms salt bridge with JNK1 Arg263, whereas the corresponding residue Thr432 in MKP5-CD may not interact with JNK1.	RESULTS
98	102	MKP5	protein	Asp268 of MKP7-CD forms salt bridge with JNK1 Arg263, whereas the corresponding residue Thr432 in MKP5-CD may not interact with JNK1.	RESULTS
103	105	CD	structure_element	Asp268 of MKP7-CD forms salt bridge with JNK1 Arg263, whereas the corresponding residue Thr432 in MKP5-CD may not interact with JNK1.	RESULTS
128	132	JNK1	protein	Asp268 of MKP7-CD forms salt bridge with JNK1 Arg263, whereas the corresponding residue Thr432 in MKP5-CD may not interact with JNK1.	RESULTS
45	49	MKP7	protein	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
50	52	CD	structure_element	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
54	60	Phe215	residue_name_number	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
62	68	Leu267	residue_name_number	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
73	79	Leu288	residue_name_number	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
124	130	Asn379	residue_name_number	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
132	138	Met431	residue_name_number	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
143	149	Met452	residue_name_number	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
153	157	MKP5	protein	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
158	160	CD	structure_element	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
213	237	hydrophobic interactions	bond_interaction	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
246	250	MKP5	protein	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
251	253	CD	structure_element	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
258	262	JNK1	protein	In addition, the key interacting residues of MKP7-CD, Phe215, Leu267 and Leu288, are replaced by less hydrophobic residues, Asn379, Met431 and Met452 in MKP5-CD (Fig. 5c), respectively, which may result in weaker hydrophobic interactions between MKP5-CD and JNK1.	RESULTS
66	70	JNK1	protein	This is consistent with the experimental observation showing that JNK1 binds to MKP7-CD much more tightly than MKP5-CD (Km value of MKP5-CD for pJNK1 substrate is ∼20-fold higher than that of MKP7-CD).	RESULTS
80	84	MKP7	protein	This is consistent with the experimental observation showing that JNK1 binds to MKP7-CD much more tightly than MKP5-CD (Km value of MKP5-CD for pJNK1 substrate is ∼20-fold higher than that of MKP7-CD).	RESULTS
85	87	CD	structure_element	This is consistent with the experimental observation showing that JNK1 binds to MKP7-CD much more tightly than MKP5-CD (Km value of MKP5-CD for pJNK1 substrate is ∼20-fold higher than that of MKP7-CD).	RESULTS
111	115	MKP5	protein	This is consistent with the experimental observation showing that JNK1 binds to MKP7-CD much more tightly than MKP5-CD (Km value of MKP5-CD for pJNK1 substrate is ∼20-fold higher than that of MKP7-CD).	RESULTS
116	118	CD	structure_element	This is consistent with the experimental observation showing that JNK1 binds to MKP7-CD much more tightly than MKP5-CD (Km value of MKP5-CD for pJNK1 substrate is ∼20-fold higher than that of MKP7-CD).	RESULTS
132	136	MKP5	protein	This is consistent with the experimental observation showing that JNK1 binds to MKP7-CD much more tightly than MKP5-CD (Km value of MKP5-CD for pJNK1 substrate is ∼20-fold higher than that of MKP7-CD).	RESULTS
137	139	CD	structure_element	This is consistent with the experimental observation showing that JNK1 binds to MKP7-CD much more tightly than MKP5-CD (Km value of MKP5-CD for pJNK1 substrate is ∼20-fold higher than that of MKP7-CD).	RESULTS
144	145	p	protein_state	This is consistent with the experimental observation showing that JNK1 binds to MKP7-CD much more tightly than MKP5-CD (Km value of MKP5-CD for pJNK1 substrate is ∼20-fold higher than that of MKP7-CD).	RESULTS
145	149	JNK1	protein	This is consistent with the experimental observation showing that JNK1 binds to MKP7-CD much more tightly than MKP5-CD (Km value of MKP5-CD for pJNK1 substrate is ∼20-fold higher than that of MKP7-CD).	RESULTS
192	196	MKP7	protein	This is consistent with the experimental observation showing that JNK1 binds to MKP7-CD much more tightly than MKP5-CD (Km value of MKP5-CD for pJNK1 substrate is ∼20-fold higher than that of MKP7-CD).	RESULTS
197	199	CD	structure_element	This is consistent with the experimental observation showing that JNK1 binds to MKP7-CD much more tightly than MKP5-CD (Km value of MKP5-CD for pJNK1 substrate is ∼20-fold higher than that of MKP7-CD).	RESULTS
4	9	MAPKs	protein_type	The MAPKs p38, ERK and JNK, are central to evolutionarily conserved signalling pathways that are present in all eukaryotic cells.	DISCUSS
10	13	p38	protein_type	The MAPKs p38, ERK and JNK, are central to evolutionarily conserved signalling pathways that are present in all eukaryotic cells.	DISCUSS
15	18	ERK	protein_type	The MAPKs p38, ERK and JNK, are central to evolutionarily conserved signalling pathways that are present in all eukaryotic cells.	DISCUSS
23	26	JNK	protein_type	The MAPKs p38, ERK and JNK, are central to evolutionarily conserved signalling pathways that are present in all eukaryotic cells.	DISCUSS
112	122	eukaryotic	taxonomy_domain	The MAPKs p38, ERK and JNK, are central to evolutionarily conserved signalling pathways that are present in all eukaryotic cells.	DISCUSS
5	9	MAPK	protein_type	Each MAPK cascade is activated in response to a diverse array of extracellular signals and culminates in the dual-phosphorylation of a threonine and a tyrosine residue in the MAPK-activation loop.	DISCUSS
109	129	dual-phosphorylation	ptm	Each MAPK cascade is activated in response to a diverse array of extracellular signals and culminates in the dual-phosphorylation of a threonine and a tyrosine residue in the MAPK-activation loop.	DISCUSS
135	144	threonine	residue_name	Each MAPK cascade is activated in response to a diverse array of extracellular signals and culminates in the dual-phosphorylation of a threonine and a tyrosine residue in the MAPK-activation loop.	DISCUSS
151	159	tyrosine	residue_name	Each MAPK cascade is activated in response to a diverse array of extracellular signals and culminates in the dual-phosphorylation of a threonine and a tyrosine residue in the MAPK-activation loop.	DISCUSS
175	195	MAPK-activation loop	structure_element	Each MAPK cascade is activated in response to a diverse array of extracellular signals and culminates in the dual-phosphorylation of a threonine and a tyrosine residue in the MAPK-activation loop.	DISCUSS
19	23	MAPK	protein_type	The propagation of MAPK signals is attenuated through the actions of the MKPs.	DISCUSS
73	77	MKPs	protein_type	The propagation of MAPK signals is attenuated through the actions of the MKPs.	DISCUSS
54	59	MAPKs	protein_type	Most studies have focused on the dephosphorylation of MAPKs by phosphatases containing the ‘kinase-interaction motif ' (D-motif), including a group of DUSPs (MKPs) and a distinct subfamily of tyrosine phosphatases (HePTP, STEP and PTP-SL).	DISCUSS
63	75	phosphatases	protein_type	Most studies have focused on the dephosphorylation of MAPKs by phosphatases containing the ‘kinase-interaction motif ' (D-motif), including a group of DUSPs (MKPs) and a distinct subfamily of tyrosine phosphatases (HePTP, STEP and PTP-SL).	DISCUSS
92	116	kinase-interaction motif	structure_element	Most studies have focused on the dephosphorylation of MAPKs by phosphatases containing the ‘kinase-interaction motif ' (D-motif), including a group of DUSPs (MKPs) and a distinct subfamily of tyrosine phosphatases (HePTP, STEP and PTP-SL).	DISCUSS
120	127	D-motif	structure_element	Most studies have focused on the dephosphorylation of MAPKs by phosphatases containing the ‘kinase-interaction motif ' (D-motif), including a group of DUSPs (MKPs) and a distinct subfamily of tyrosine phosphatases (HePTP, STEP and PTP-SL).	DISCUSS
151	156	DUSPs	protein_type	Most studies have focused on the dephosphorylation of MAPKs by phosphatases containing the ‘kinase-interaction motif ' (D-motif), including a group of DUSPs (MKPs) and a distinct subfamily of tyrosine phosphatases (HePTP, STEP and PTP-SL).	DISCUSS
158	162	MKPs	protein_type	Most studies have focused on the dephosphorylation of MAPKs by phosphatases containing the ‘kinase-interaction motif ' (D-motif), including a group of DUSPs (MKPs) and a distinct subfamily of tyrosine phosphatases (HePTP, STEP and PTP-SL).	DISCUSS
192	213	tyrosine phosphatases	protein_type	Most studies have focused on the dephosphorylation of MAPKs by phosphatases containing the ‘kinase-interaction motif ' (D-motif), including a group of DUSPs (MKPs) and a distinct subfamily of tyrosine phosphatases (HePTP, STEP and PTP-SL).	DISCUSS
215	220	HePTP	protein	Most studies have focused on the dephosphorylation of MAPKs by phosphatases containing the ‘kinase-interaction motif ' (D-motif), including a group of DUSPs (MKPs) and a distinct subfamily of tyrosine phosphatases (HePTP, STEP and PTP-SL).	DISCUSS
222	226	STEP	protein	Most studies have focused on the dephosphorylation of MAPKs by phosphatases containing the ‘kinase-interaction motif ' (D-motif), including a group of DUSPs (MKPs) and a distinct subfamily of tyrosine phosphatases (HePTP, STEP and PTP-SL).	DISCUSS
231	237	PTP-SL	protein	Most studies have focused on the dephosphorylation of MAPKs by phosphatases containing the ‘kinase-interaction motif ' (D-motif), including a group of DUSPs (MKPs) and a distinct subfamily of tyrosine phosphatases (HePTP, STEP and PTP-SL).	DISCUSS
0	18	Crystal structures	evidence	Crystal structures of ERK2 bound with the D-motif sequences derived from MKP3 and HePTP have been reported.	DISCUSS
22	26	ERK2	protein	Crystal structures of ERK2 bound with the D-motif sequences derived from MKP3 and HePTP have been reported.	DISCUSS
27	37	bound with	protein_state	Crystal structures of ERK2 bound with the D-motif sequences derived from MKP3 and HePTP have been reported.	DISCUSS
42	49	D-motif	structure_element	Crystal structures of ERK2 bound with the D-motif sequences derived from MKP3 and HePTP have been reported.	DISCUSS
73	77	MKP3	protein	Crystal structures of ERK2 bound with the D-motif sequences derived from MKP3 and HePTP have been reported.	DISCUSS
82	87	HePTP	protein	Crystal structures of ERK2 bound with the D-motif sequences derived from MKP3 and HePTP have been reported.	DISCUSS
6	16	structures	evidence	These structures revealed that linear docking motifs in interacting proteins bind to a common docking site on MAPKs outside the kinase active site.	DISCUSS
31	52	linear docking motifs	structure_element	These structures revealed that linear docking motifs in interacting proteins bind to a common docking site on MAPKs outside the kinase active site.	DISCUSS
94	106	docking site	site	These structures revealed that linear docking motifs in interacting proteins bind to a common docking site on MAPKs outside the kinase active site.	DISCUSS
110	115	MAPKs	protein_type	These structures revealed that linear docking motifs in interacting proteins bind to a common docking site on MAPKs outside the kinase active site.	DISCUSS
128	134	kinase	protein_type	These structures revealed that linear docking motifs in interacting proteins bind to a common docking site on MAPKs outside the kinase active site.	DISCUSS
135	146	active site	site	These structures revealed that linear docking motifs in interacting proteins bind to a common docking site on MAPKs outside the kinase active site.	DISCUSS
52	59	D-motif	structure_element	The particular amino acids and their spacing within D-motif sequences and amino acid composition of the docking sites on MAPKs appear to determine the specificity of D-motifs for individual MAPKs.	DISCUSS
104	117	docking sites	site	The particular amino acids and their spacing within D-motif sequences and amino acid composition of the docking sites on MAPKs appear to determine the specificity of D-motifs for individual MAPKs.	DISCUSS
121	126	MAPKs	protein_type	The particular amino acids and their spacing within D-motif sequences and amino acid composition of the docking sites on MAPKs appear to determine the specificity of D-motifs for individual MAPKs.	DISCUSS
166	174	D-motifs	structure_element	The particular amino acids and their spacing within D-motif sequences and amino acid composition of the docking sites on MAPKs appear to determine the specificity of D-motifs for individual MAPKs.	DISCUSS
190	195	MAPKs	protein_type	The particular amino acids and their spacing within D-motif sequences and amino acid composition of the docking sites on MAPKs appear to determine the specificity of D-motifs for individual MAPKs.	DISCUSS
14	31	crystal structure	evidence	Recently, the crystal structure of a complex between the KBD of MKP5 and p38α has been obtained.	DISCUSS
57	60	KBD	structure_element	Recently, the crystal structure of a complex between the KBD of MKP5 and p38α has been obtained.	DISCUSS
64	68	MKP5	protein	Recently, the crystal structure of a complex between the KBD of MKP5 and p38α has been obtained.	DISCUSS
73	77	p38α	protein	Recently, the crystal structure of a complex between the KBD of MKP5 and p38α has been obtained.	DISCUSS
58	62	MKP5	protein	This complex has revealed a distinct interaction mode for MKP5.	DISCUSS
4	7	KBD	structure_element	The KBD of MKP5 binds to p38α in the opposite polypeptide direction compared with how the D-motif of MKP3 binds to ERK2.	DISCUSS
11	15	MKP5	protein	The KBD of MKP5 binds to p38α in the opposite polypeptide direction compared with how the D-motif of MKP3 binds to ERK2.	DISCUSS
25	29	p38α	protein	The KBD of MKP5 binds to p38α in the opposite polypeptide direction compared with how the D-motif of MKP3 binds to ERK2.	DISCUSS
90	97	D-motif	structure_element	The KBD of MKP5 binds to p38α in the opposite polypeptide direction compared with how the D-motif of MKP3 binds to ERK2.	DISCUSS
101	105	MKP3	protein	The KBD of MKP5 binds to p38α in the opposite polypeptide direction compared with how the D-motif of MKP3 binds to ERK2.	DISCUSS
115	119	ERK2	protein	The KBD of MKP5 binds to p38α in the opposite polypeptide direction compared with how the D-motif of MKP3 binds to ERK2.	DISCUSS
29	49	D-motif-binding mode	site	In contrast to the canonical D-motif-binding mode, separate helices, α2 and α3′, in the KBD of MKP5 engage the p38α-docking site.	DISCUSS
60	67	helices	structure_element	In contrast to the canonical D-motif-binding mode, separate helices, α2 and α3′, in the KBD of MKP5 engage the p38α-docking site.	DISCUSS
69	71	α2	structure_element	In contrast to the canonical D-motif-binding mode, separate helices, α2 and α3′, in the KBD of MKP5 engage the p38α-docking site.	DISCUSS
76	79	α3′	structure_element	In contrast to the canonical D-motif-binding mode, separate helices, α2 and α3′, in the KBD of MKP5 engage the p38α-docking site.	DISCUSS
88	91	KBD	structure_element	In contrast to the canonical D-motif-binding mode, separate helices, α2 and α3′, in the KBD of MKP5 engage the p38α-docking site.	DISCUSS
95	99	MKP5	protein	In contrast to the canonical D-motif-binding mode, separate helices, α2 and α3′, in the KBD of MKP5 engage the p38α-docking site.	DISCUSS
111	128	p38α-docking site	site	In contrast to the canonical D-motif-binding mode, separate helices, α2 and α3′, in the KBD of MKP5 engage the p38α-docking site.	DISCUSS
8	42	structural and biochemical studies	experimental_method	Further structural and biochemical studies indicate that KBD of MKP7 may interact with p38α in a similar manner to that of MKP5.	DISCUSS
57	60	KBD	structure_element	Further structural and biochemical studies indicate that KBD of MKP7 may interact with p38α in a similar manner to that of MKP5.	DISCUSS
64	68	MKP7	protein	Further structural and biochemical studies indicate that KBD of MKP7 may interact with p38α in a similar manner to that of MKP5.	DISCUSS
87	91	p38α	protein	Further structural and biochemical studies indicate that KBD of MKP7 may interact with p38α in a similar manner to that of MKP5.	DISCUSS
123	127	MKP5	protein	Further structural and biochemical studies indicate that KBD of MKP7 may interact with p38α in a similar manner to that of MKP5.	DISCUSS
15	19	MKP5	protein	In contrast to MKP5, removal of the KBD domain from MKP7 does not drastically affect enzyme catalysis, and the kinetic parameters of MKP7-CD for p38α substrate are very similar to those for JNK1 substrate.	DISCUSS
21	31	removal of	experimental_method	In contrast to MKP5, removal of the KBD domain from MKP7 does not drastically affect enzyme catalysis, and the kinetic parameters of MKP7-CD for p38α substrate are very similar to those for JNK1 substrate.	DISCUSS
36	39	KBD	structure_element	In contrast to MKP5, removal of the KBD domain from MKP7 does not drastically affect enzyme catalysis, and the kinetic parameters of MKP7-CD for p38α substrate are very similar to those for JNK1 substrate.	DISCUSS
52	56	MKP7	protein	In contrast to MKP5, removal of the KBD domain from MKP7 does not drastically affect enzyme catalysis, and the kinetic parameters of MKP7-CD for p38α substrate are very similar to those for JNK1 substrate.	DISCUSS
133	137	MKP7	protein	In contrast to MKP5, removal of the KBD domain from MKP7 does not drastically affect enzyme catalysis, and the kinetic parameters of MKP7-CD for p38α substrate are very similar to those for JNK1 substrate.	DISCUSS
138	140	CD	structure_element	In contrast to MKP5, removal of the KBD domain from MKP7 does not drastically affect enzyme catalysis, and the kinetic parameters of MKP7-CD for p38α substrate are very similar to those for JNK1 substrate.	DISCUSS
145	149	p38α	protein	In contrast to MKP5, removal of the KBD domain from MKP7 does not drastically affect enzyme catalysis, and the kinetic parameters of MKP7-CD for p38α substrate are very similar to those for JNK1 substrate.	DISCUSS
190	194	JNK1	protein	In contrast to MKP5, removal of the KBD domain from MKP7 does not drastically affect enzyme catalysis, and the kinetic parameters of MKP7-CD for p38α substrate are very similar to those for JNK1 substrate.	DISCUSS
43	47	MKP7	protein	Taken together, these results suggest that MKP7 utilizes a bipartite recognition mechanism to achieve the efficiency and fidelity of p38α signalling.	DISCUSS
133	137	p38α	protein	Taken together, these results suggest that MKP7 utilizes a bipartite recognition mechanism to achieve the efficiency and fidelity of p38α signalling.	DISCUSS
4	8	MKP7	protein	The MKP7-KBD docks to the D-site located on the back side of the p38α catalytic pocket for high-affinity association, whereas the interaction of the MKP7-CD with another p38α structural region, which is close to the activation loop, may not only stabilize binding but also provide contacts crucial for organizing the MKP7 active site with respect to the phosphoreceptor in the p38α substrate for efficient dephosphorylation.	DISCUSS
9	12	KBD	structure_element	The MKP7-KBD docks to the D-site located on the back side of the p38α catalytic pocket for high-affinity association, whereas the interaction of the MKP7-CD with another p38α structural region, which is close to the activation loop, may not only stabilize binding but also provide contacts crucial for organizing the MKP7 active site with respect to the phosphoreceptor in the p38α substrate for efficient dephosphorylation.	DISCUSS
26	32	D-site	site	The MKP7-KBD docks to the D-site located on the back side of the p38α catalytic pocket for high-affinity association, whereas the interaction of the MKP7-CD with another p38α structural region, which is close to the activation loop, may not only stabilize binding but also provide contacts crucial for organizing the MKP7 active site with respect to the phosphoreceptor in the p38α substrate for efficient dephosphorylation.	DISCUSS
65	69	p38α	protein	The MKP7-KBD docks to the D-site located on the back side of the p38α catalytic pocket for high-affinity association, whereas the interaction of the MKP7-CD with another p38α structural region, which is close to the activation loop, may not only stabilize binding but also provide contacts crucial for organizing the MKP7 active site with respect to the phosphoreceptor in the p38α substrate for efficient dephosphorylation.	DISCUSS
70	86	catalytic pocket	site	The MKP7-KBD docks to the D-site located on the back side of the p38α catalytic pocket for high-affinity association, whereas the interaction of the MKP7-CD with another p38α structural region, which is close to the activation loop, may not only stabilize binding but also provide contacts crucial for organizing the MKP7 active site with respect to the phosphoreceptor in the p38α substrate for efficient dephosphorylation.	DISCUSS
149	153	MKP7	protein	The MKP7-KBD docks to the D-site located on the back side of the p38α catalytic pocket for high-affinity association, whereas the interaction of the MKP7-CD with another p38α structural region, which is close to the activation loop, may not only stabilize binding but also provide contacts crucial for organizing the MKP7 active site with respect to the phosphoreceptor in the p38α substrate for efficient dephosphorylation.	DISCUSS
154	156	CD	structure_element	The MKP7-KBD docks to the D-site located on the back side of the p38α catalytic pocket for high-affinity association, whereas the interaction of the MKP7-CD with another p38α structural region, which is close to the activation loop, may not only stabilize binding but also provide contacts crucial for organizing the MKP7 active site with respect to the phosphoreceptor in the p38α substrate for efficient dephosphorylation.	DISCUSS
170	174	p38α	protein	The MKP7-KBD docks to the D-site located on the back side of the p38α catalytic pocket for high-affinity association, whereas the interaction of the MKP7-CD with another p38α structural region, which is close to the activation loop, may not only stabilize binding but also provide contacts crucial for organizing the MKP7 active site with respect to the phosphoreceptor in the p38α substrate for efficient dephosphorylation.	DISCUSS
216	231	activation loop	structure_element	The MKP7-KBD docks to the D-site located on the back side of the p38α catalytic pocket for high-affinity association, whereas the interaction of the MKP7-CD with another p38α structural region, which is close to the activation loop, may not only stabilize binding but also provide contacts crucial for organizing the MKP7 active site with respect to the phosphoreceptor in the p38α substrate for efficient dephosphorylation.	DISCUSS
317	321	MKP7	protein	The MKP7-KBD docks to the D-site located on the back side of the p38α catalytic pocket for high-affinity association, whereas the interaction of the MKP7-CD with another p38α structural region, which is close to the activation loop, may not only stabilize binding but also provide contacts crucial for organizing the MKP7 active site with respect to the phosphoreceptor in the p38α substrate for efficient dephosphorylation.	DISCUSS
322	333	active site	site	The MKP7-KBD docks to the D-site located on the back side of the p38α catalytic pocket for high-affinity association, whereas the interaction of the MKP7-CD with another p38α structural region, which is close to the activation loop, may not only stabilize binding but also provide contacts crucial for organizing the MKP7 active site with respect to the phosphoreceptor in the p38α substrate for efficient dephosphorylation.	DISCUSS
377	381	p38α	protein	The MKP7-KBD docks to the D-site located on the back side of the p38α catalytic pocket for high-affinity association, whereas the interaction of the MKP7-CD with another p38α structural region, which is close to the activation loop, may not only stabilize binding but also provide contacts crucial for organizing the MKP7 active site with respect to the phosphoreceptor in the p38α substrate for efficient dephosphorylation.	DISCUSS
29	35	D-site	site	In addition to the canonical D-site, the MAPK ERK2 contains a second binding site utilized by transcription factor substrates and phosphatases, the FXF-motif-binding site (also called F-site), that is exposed in active ERK2 and the D-motif peptide-induced conformation of MAPKs.	DISCUSS
41	45	MAPK	protein_type	In addition to the canonical D-site, the MAPK ERK2 contains a second binding site utilized by transcription factor substrates and phosphatases, the FXF-motif-binding site (also called F-site), that is exposed in active ERK2 and the D-motif peptide-induced conformation of MAPKs.	DISCUSS
46	50	ERK2	protein	In addition to the canonical D-site, the MAPK ERK2 contains a second binding site utilized by transcription factor substrates and phosphatases, the FXF-motif-binding site (also called F-site), that is exposed in active ERK2 and the D-motif peptide-induced conformation of MAPKs.	DISCUSS
62	81	second binding site	site	In addition to the canonical D-site, the MAPK ERK2 contains a second binding site utilized by transcription factor substrates and phosphatases, the FXF-motif-binding site (also called F-site), that is exposed in active ERK2 and the D-motif peptide-induced conformation of MAPKs.	DISCUSS
130	142	phosphatases	protein_type	In addition to the canonical D-site, the MAPK ERK2 contains a second binding site utilized by transcription factor substrates and phosphatases, the FXF-motif-binding site (also called F-site), that is exposed in active ERK2 and the D-motif peptide-induced conformation of MAPKs.	DISCUSS
148	170	FXF-motif-binding site	site	In addition to the canonical D-site, the MAPK ERK2 contains a second binding site utilized by transcription factor substrates and phosphatases, the FXF-motif-binding site (also called F-site), that is exposed in active ERK2 and the D-motif peptide-induced conformation of MAPKs.	DISCUSS
184	190	F-site	site	In addition to the canonical D-site, the MAPK ERK2 contains a second binding site utilized by transcription factor substrates and phosphatases, the FXF-motif-binding site (also called F-site), that is exposed in active ERK2 and the D-motif peptide-induced conformation of MAPKs.	DISCUSS
212	218	active	protein_state	In addition to the canonical D-site, the MAPK ERK2 contains a second binding site utilized by transcription factor substrates and phosphatases, the FXF-motif-binding site (also called F-site), that is exposed in active ERK2 and the D-motif peptide-induced conformation of MAPKs.	DISCUSS
219	223	ERK2	protein	In addition to the canonical D-site, the MAPK ERK2 contains a second binding site utilized by transcription factor substrates and phosphatases, the FXF-motif-binding site (also called F-site), that is exposed in active ERK2 and the D-motif peptide-induced conformation of MAPKs.	DISCUSS
232	239	D-motif	structure_element	In addition to the canonical D-site, the MAPK ERK2 contains a second binding site utilized by transcription factor substrates and phosphatases, the FXF-motif-binding site (also called F-site), that is exposed in active ERK2 and the D-motif peptide-induced conformation of MAPKs.	DISCUSS
272	277	MAPKs	protein_type	In addition to the canonical D-site, the MAPK ERK2 contains a second binding site utilized by transcription factor substrates and phosphatases, the FXF-motif-binding site (also called F-site), that is exposed in active ERK2 and the D-motif peptide-induced conformation of MAPKs.	DISCUSS
5	21	hydrophobic site	site	This hydrophobic site was first identified by changes in deuterium exchange profiles, and is near the MAPK insertion and helix αG. Interestingly, many of the equivalent residues in JNK1, important for MKP7-CD recognition, are also used for substrate binding by ERK2 (ref.), indicating that this site is overlapped with the DEF-site previously identified in ERK2 (Fig. 5d).	DISCUSS
46	84	changes in deuterium exchange profiles	evidence	This hydrophobic site was first identified by changes in deuterium exchange profiles, and is near the MAPK insertion and helix αG. Interestingly, many of the equivalent residues in JNK1, important for MKP7-CD recognition, are also used for substrate binding by ERK2 (ref.), indicating that this site is overlapped with the DEF-site previously identified in ERK2 (Fig. 5d).	DISCUSS
102	116	MAPK insertion	structure_element	This hydrophobic site was first identified by changes in deuterium exchange profiles, and is near the MAPK insertion and helix αG. Interestingly, many of the equivalent residues in JNK1, important for MKP7-CD recognition, are also used for substrate binding by ERK2 (ref.), indicating that this site is overlapped with the DEF-site previously identified in ERK2 (Fig. 5d).	DISCUSS
121	126	helix	structure_element	This hydrophobic site was first identified by changes in deuterium exchange profiles, and is near the MAPK insertion and helix αG. Interestingly, many of the equivalent residues in JNK1, important for MKP7-CD recognition, are also used for substrate binding by ERK2 (ref.), indicating that this site is overlapped with the DEF-site previously identified in ERK2 (Fig. 5d).	DISCUSS
127	129	αG	structure_element	This hydrophobic site was first identified by changes in deuterium exchange profiles, and is near the MAPK insertion and helix αG. Interestingly, many of the equivalent residues in JNK1, important for MKP7-CD recognition, are also used for substrate binding by ERK2 (ref.), indicating that this site is overlapped with the DEF-site previously identified in ERK2 (Fig. 5d).	DISCUSS
181	185	JNK1	protein	This hydrophobic site was first identified by changes in deuterium exchange profiles, and is near the MAPK insertion and helix αG. Interestingly, many of the equivalent residues in JNK1, important for MKP7-CD recognition, are also used for substrate binding by ERK2 (ref.), indicating that this site is overlapped with the DEF-site previously identified in ERK2 (Fig. 5d).	DISCUSS
201	205	MKP7	protein	This hydrophobic site was first identified by changes in deuterium exchange profiles, and is near the MAPK insertion and helix αG. Interestingly, many of the equivalent residues in JNK1, important for MKP7-CD recognition, are also used for substrate binding by ERK2 (ref.), indicating that this site is overlapped with the DEF-site previously identified in ERK2 (Fig. 5d).	DISCUSS
206	208	CD	structure_element	This hydrophobic site was first identified by changes in deuterium exchange profiles, and is near the MAPK insertion and helix αG. Interestingly, many of the equivalent residues in JNK1, important for MKP7-CD recognition, are also used for substrate binding by ERK2 (ref.), indicating that this site is overlapped with the DEF-site previously identified in ERK2 (Fig. 5d).	DISCUSS
261	265	ERK2	protein	This hydrophobic site was first identified by changes in deuterium exchange profiles, and is near the MAPK insertion and helix αG. Interestingly, many of the equivalent residues in JNK1, important for MKP7-CD recognition, are also used for substrate binding by ERK2 (ref.), indicating that this site is overlapped with the DEF-site previously identified in ERK2 (Fig. 5d).	DISCUSS
323	331	DEF-site	site	This hydrophobic site was first identified by changes in deuterium exchange profiles, and is near the MAPK insertion and helix αG. Interestingly, many of the equivalent residues in JNK1, important for MKP7-CD recognition, are also used for substrate binding by ERK2 (ref.), indicating that this site is overlapped with the DEF-site previously identified in ERK2 (Fig. 5d).	DISCUSS
357	361	ERK2	protein	This hydrophobic site was first identified by changes in deuterium exchange profiles, and is near the MAPK insertion and helix αG. Interestingly, many of the equivalent residues in JNK1, important for MKP7-CD recognition, are also used for substrate binding by ERK2 (ref.), indicating that this site is overlapped with the DEF-site previously identified in ERK2 (Fig. 5d).	DISCUSS
0	4	MKP3	protein	MKP3 is highly specific in dephosphorylating and inactivating ERK2, and the phosphatase activity of the MKP3-catalysed pNPP reaction can be markedly increased in the presence of ERK2 (refs).	DISCUSS
62	66	ERK2	protein	MKP3 is highly specific in dephosphorylating and inactivating ERK2, and the phosphatase activity of the MKP3-catalysed pNPP reaction can be markedly increased in the presence of ERK2 (refs).	DISCUSS
104	108	MKP3	protein	MKP3 is highly specific in dephosphorylating and inactivating ERK2, and the phosphatase activity of the MKP3-catalysed pNPP reaction can be markedly increased in the presence of ERK2 (refs).	DISCUSS
119	123	pNPP	chemical	MKP3 is highly specific in dephosphorylating and inactivating ERK2, and the phosphatase activity of the MKP3-catalysed pNPP reaction can be markedly increased in the presence of ERK2 (refs).	DISCUSS
166	177	presence of	protein_state	MKP3 is highly specific in dephosphorylating and inactivating ERK2, and the phosphatase activity of the MKP3-catalysed pNPP reaction can be markedly increased in the presence of ERK2 (refs).	DISCUSS
178	182	ERK2	protein	MKP3 is highly specific in dephosphorylating and inactivating ERK2, and the phosphatase activity of the MKP3-catalysed pNPP reaction can be markedly increased in the presence of ERK2 (refs).	DISCUSS
0	18	Sequence alignment	experimental_method	Sequence alignment of all MKPs reveals a high degree of conservation of residues surrounding the interacting region observed in JNK1–MKP7-CD complex (Supplementary Fig. 5).	DISCUSS
26	30	MKPs	protein_type	Sequence alignment of all MKPs reveals a high degree of conservation of residues surrounding the interacting region observed in JNK1–MKP7-CD complex (Supplementary Fig. 5).	DISCUSS
97	115	interacting region	site	Sequence alignment of all MKPs reveals a high degree of conservation of residues surrounding the interacting region observed in JNK1–MKP7-CD complex (Supplementary Fig. 5).	DISCUSS
128	140	JNK1–MKP7-CD	complex_assembly	Sequence alignment of all MKPs reveals a high degree of conservation of residues surrounding the interacting region observed in JNK1–MKP7-CD complex (Supplementary Fig. 5).	DISCUSS
48	64	catalytic domain	structure_element	Therefore, it is tempting to speculate that the catalytic domain of MKP3 may bind to ERK2 in a manner analogous to the way by which MKP7-CD binds to JNK1.	DISCUSS
68	72	MKP3	protein	Therefore, it is tempting to speculate that the catalytic domain of MKP3 may bind to ERK2 in a manner analogous to the way by which MKP7-CD binds to JNK1.	DISCUSS
85	89	ERK2	protein	Therefore, it is tempting to speculate that the catalytic domain of MKP3 may bind to ERK2 in a manner analogous to the way by which MKP7-CD binds to JNK1.	DISCUSS
132	136	MKP7	protein	Therefore, it is tempting to speculate that the catalytic domain of MKP3 may bind to ERK2 in a manner analogous to the way by which MKP7-CD binds to JNK1.	DISCUSS
137	139	CD	structure_element	Therefore, it is tempting to speculate that the catalytic domain of MKP3 may bind to ERK2 in a manner analogous to the way by which MKP7-CD binds to JNK1.	DISCUSS
149	153	JNK1	protein	Therefore, it is tempting to speculate that the catalytic domain of MKP3 may bind to ERK2 in a manner analogous to the way by which MKP7-CD binds to JNK1.	DISCUSS
67	71	ERK2	protein	A comprehensive examination of the molecular basis of the specific ERK2 recognition by MKP3 is underway.	DISCUSS
87	91	MKP3	protein	A comprehensive examination of the molecular basis of the specific ERK2 recognition by MKP3 is underway.	DISCUSS
98	110	JNK1–MKP7-CD	complex_assembly	The ongoing work demonstrates that although the overall interaction modes are similar between the JNK1–MKP7-CD and ERK2–MKP3-CD complexes, the ERK2–MKP3-CD interaction is less extensive and helix α4 from MKP3-CD does not interact directly with ERK2.	DISCUSS
115	127	ERK2–MKP3-CD	complex_assembly	The ongoing work demonstrates that although the overall interaction modes are similar between the JNK1–MKP7-CD and ERK2–MKP3-CD complexes, the ERK2–MKP3-CD interaction is less extensive and helix α4 from MKP3-CD does not interact directly with ERK2.	DISCUSS
143	155	ERK2–MKP3-CD	complex_assembly	The ongoing work demonstrates that although the overall interaction modes are similar between the JNK1–MKP7-CD and ERK2–MKP3-CD complexes, the ERK2–MKP3-CD interaction is less extensive and helix α4 from MKP3-CD does not interact directly with ERK2.	DISCUSS
190	195	helix	structure_element	The ongoing work demonstrates that although the overall interaction modes are similar between the JNK1–MKP7-CD and ERK2–MKP3-CD complexes, the ERK2–MKP3-CD interaction is less extensive and helix α4 from MKP3-CD does not interact directly with ERK2.	DISCUSS
196	198	α4	structure_element	The ongoing work demonstrates that although the overall interaction modes are similar between the JNK1–MKP7-CD and ERK2–MKP3-CD complexes, the ERK2–MKP3-CD interaction is less extensive and helix α4 from MKP3-CD does not interact directly with ERK2.	DISCUSS
204	208	MKP3	protein	The ongoing work demonstrates that although the overall interaction modes are similar between the JNK1–MKP7-CD and ERK2–MKP3-CD complexes, the ERK2–MKP3-CD interaction is less extensive and helix α4 from MKP3-CD does not interact directly with ERK2.	DISCUSS
209	211	CD	structure_element	The ongoing work demonstrates that although the overall interaction modes are similar between the JNK1–MKP7-CD and ERK2–MKP3-CD complexes, the ERK2–MKP3-CD interaction is less extensive and helix α4 from MKP3-CD does not interact directly with ERK2.	DISCUSS
244	248	ERK2	protein	The ongoing work demonstrates that although the overall interaction modes are similar between the JNK1–MKP7-CD and ERK2–MKP3-CD complexes, the ERK2–MKP3-CD interaction is less extensive and helix α4 from MKP3-CD does not interact directly with ERK2.	DISCUSS
4	13	FXF-motif	structure_element	The FXF-motif-mediated interaction is critical for both pERK2 inactivation and ERK2-induced MKP3 activation (manuscript in preparation).	DISCUSS
56	57	p	protein_state	The FXF-motif-mediated interaction is critical for both pERK2 inactivation and ERK2-induced MKP3 activation (manuscript in preparation).	DISCUSS
57	61	ERK2	protein	The FXF-motif-mediated interaction is critical for both pERK2 inactivation and ERK2-induced MKP3 activation (manuscript in preparation).	DISCUSS
79	83	ERK2	protein	The FXF-motif-mediated interaction is critical for both pERK2 inactivation and ERK2-induced MKP3 activation (manuscript in preparation).	DISCUSS
92	96	MKP3	protein	The FXF-motif-mediated interaction is critical for both pERK2 inactivation and ERK2-induced MKP3 activation (manuscript in preparation).	DISCUSS
33	42	structure	evidence	In summary, we have resolved the structure of JNK1 in complex with the catalytic domain of MKP7.	DISCUSS
46	50	JNK1	protein	In summary, we have resolved the structure of JNK1 in complex with the catalytic domain of MKP7.	DISCUSS
51	66	in complex with	protein_state	In summary, we have resolved the structure of JNK1 in complex with the catalytic domain of MKP7.	DISCUSS
71	87	catalytic domain	structure_element	In summary, we have resolved the structure of JNK1 in complex with the catalytic domain of MKP7.	DISCUSS
91	95	MKP7	protein	In summary, we have resolved the structure of JNK1 in complex with the catalytic domain of MKP7.	DISCUSS
5	14	structure	evidence	This structure reveals an FXF-docking interaction mode between MAPK and MKP.	DISCUSS
26	54	FXF-docking interaction mode	site	This structure reveals an FXF-docking interaction mode between MAPK and MKP.	DISCUSS
63	67	MAPK	protein_type	This structure reveals an FXF-docking interaction mode between MAPK and MKP.	DISCUSS
72	75	MKP	protein_type	This structure reveals an FXF-docking interaction mode between MAPK and MKP.	DISCUSS
13	41	biochemical characterization	experimental_method	Results from biochemical characterization of the Phe285 and Phe287 MKP7 mutants combined with structural information support the conclusion that the two Phe residues serve different roles in the catalytic reaction.	DISCUSS
49	55	Phe285	residue_name_number	Results from biochemical characterization of the Phe285 and Phe287 MKP7 mutants combined with structural information support the conclusion that the two Phe residues serve different roles in the catalytic reaction.	DISCUSS
60	66	Phe287	residue_name_number	Results from biochemical characterization of the Phe285 and Phe287 MKP7 mutants combined with structural information support the conclusion that the two Phe residues serve different roles in the catalytic reaction.	DISCUSS
67	71	MKP7	protein	Results from biochemical characterization of the Phe285 and Phe287 MKP7 mutants combined with structural information support the conclusion that the two Phe residues serve different roles in the catalytic reaction.	DISCUSS
72	79	mutants	protein_state	Results from biochemical characterization of the Phe285 and Phe287 MKP7 mutants combined with structural information support the conclusion that the two Phe residues serve different roles in the catalytic reaction.	DISCUSS
94	116	structural information	evidence	Results from biochemical characterization of the Phe285 and Phe287 MKP7 mutants combined with structural information support the conclusion that the two Phe residues serve different roles in the catalytic reaction.	DISCUSS
153	156	Phe	residue_name	Results from biochemical characterization of the Phe285 and Phe287 MKP7 mutants combined with structural information support the conclusion that the two Phe residues serve different roles in the catalytic reaction.	DISCUSS
0	6	Phe285	residue_name_number	Phe285 is essential for JNK1 substrate binding, whereas Phe287 plays a role for the precise alignment of active-site residues, which are important for transition-state stabilization.	DISCUSS
24	28	JNK1	protein	Phe285 is essential for JNK1 substrate binding, whereas Phe287 plays a role for the precise alignment of active-site residues, which are important for transition-state stabilization.	DISCUSS
56	62	Phe287	residue_name_number	Phe285 is essential for JNK1 substrate binding, whereas Phe287 plays a role for the precise alignment of active-site residues, which are important for transition-state stabilization.	DISCUSS
105	125	active-site residues	site	Phe285 is essential for JNK1 substrate binding, whereas Phe287 plays a role for the precise alignment of active-site residues, which are important for transition-state stabilization.	DISCUSS
22	36	FXF-type motif	structure_element	This newly identified FXF-type motif is present in all MKPs, except that the residue at the first position in MKP5 is an equivalent hydrophobic leucine residue (see also Fig. 7f,g), suggesting that these two Phe residues would play a similar role in facilitating substrate recognition and catalysis, respectively.	DISCUSS
55	59	MKPs	protein_type	This newly identified FXF-type motif is present in all MKPs, except that the residue at the first position in MKP5 is an equivalent hydrophobic leucine residue (see also Fig. 7f,g), suggesting that these two Phe residues would play a similar role in facilitating substrate recognition and catalysis, respectively.	DISCUSS
110	114	MKP5	protein	This newly identified FXF-type motif is present in all MKPs, except that the residue at the first position in MKP5 is an equivalent hydrophobic leucine residue (see also Fig. 7f,g), suggesting that these two Phe residues would play a similar role in facilitating substrate recognition and catalysis, respectively.	DISCUSS
144	151	leucine	residue_name	This newly identified FXF-type motif is present in all MKPs, except that the residue at the first position in MKP5 is an equivalent hydrophobic leucine residue (see also Fig. 7f,g), suggesting that these two Phe residues would play a similar role in facilitating substrate recognition and catalysis, respectively.	DISCUSS
208	211	Phe	residue_name	This newly identified FXF-type motif is present in all MKPs, except that the residue at the first position in MKP5 is an equivalent hydrophobic leucine residue (see also Fig. 7f,g), suggesting that these two Phe residues would play a similar role in facilitating substrate recognition and catalysis, respectively.	DISCUSS
24	27	MKP	protein_type	An important feature of MKP–JNK1 interactions is that MKP7 or MKP5 only interact with the F-site of JNK1.	DISCUSS
28	32	JNK1	protein	An important feature of MKP–JNK1 interactions is that MKP7 or MKP5 only interact with the F-site of JNK1.	DISCUSS
54	58	MKP7	protein	An important feature of MKP–JNK1 interactions is that MKP7 or MKP5 only interact with the F-site of JNK1.	DISCUSS
62	66	MKP5	protein	An important feature of MKP–JNK1 interactions is that MKP7 or MKP5 only interact with the F-site of JNK1.	DISCUSS
90	96	F-site	site	An important feature of MKP–JNK1 interactions is that MKP7 or MKP5 only interact with the F-site of JNK1.	DISCUSS
100	104	JNK1	protein	An important feature of MKP–JNK1 interactions is that MKP7 or MKP5 only interact with the F-site of JNK1.	DISCUSS
33	37	JNK1	protein	One possible explanation is that JNK1 needs to use the D-site to interact with JIP-1, a scaffold protein for JNK signalling.	DISCUSS
55	61	D-site	site	One possible explanation is that JNK1 needs to use the D-site to interact with JIP-1, a scaffold protein for JNK signalling.	DISCUSS
79	84	JIP-1	protein	One possible explanation is that JNK1 needs to use the D-site to interact with JIP-1, a scaffold protein for JNK signalling.	DISCUSS
109	112	JNK	protein_type	One possible explanation is that JNK1 needs to use the D-site to interact with JIP-1, a scaffold protein for JNK signalling.	DISCUSS
15	33	JNK-binding domain	structure_element	The N-terminal JNK-binding domain of JIP-1 interacts with the D-site on JNK and this interaction is required for JIP-1-mediated enhancement of JNK activation.	DISCUSS
37	42	JIP-1	protein	The N-terminal JNK-binding domain of JIP-1 interacts with the D-site on JNK and this interaction is required for JIP-1-mediated enhancement of JNK activation.	DISCUSS
62	68	D-site	site	The N-terminal JNK-binding domain of JIP-1 interacts with the D-site on JNK and this interaction is required for JIP-1-mediated enhancement of JNK activation.	DISCUSS
72	75	JNK	protein_type	The N-terminal JNK-binding domain of JIP-1 interacts with the D-site on JNK and this interaction is required for JIP-1-mediated enhancement of JNK activation.	DISCUSS
113	118	JIP-1	protein	The N-terminal JNK-binding domain of JIP-1 interacts with the D-site on JNK and this interaction is required for JIP-1-mediated enhancement of JNK activation.	DISCUSS
143	146	JNK	protein_type	The N-terminal JNK-binding domain of JIP-1 interacts with the D-site on JNK and this interaction is required for JIP-1-mediated enhancement of JNK activation.	DISCUSS
13	18	JIP-1	protein	In addition, JIP-1 can also associate with MKP7 via the C-terminal region of MKP7 (ref.).	DISCUSS
43	47	MKP7	protein	In addition, JIP-1 can also associate with MKP7 via the C-terminal region of MKP7 (ref.).	DISCUSS
56	73	C-terminal region	structure_element	In addition, JIP-1 can also associate with MKP7 via the C-terminal region of MKP7 (ref.).	DISCUSS
77	81	MKP7	protein	In addition, JIP-1 can also associate with MKP7 via the C-terminal region of MKP7 (ref.).	DISCUSS
5	9	MKP7	protein	When MKP7 is bound to JIP-1, it reduces JNK activation, leading to reduced phosphorylation of the JNK target c-Jun.	DISCUSS
13	21	bound to	protein_state	When MKP7 is bound to JIP-1, it reduces JNK activation, leading to reduced phosphorylation of the JNK target c-Jun.	DISCUSS
22	27	JIP-1	protein	When MKP7 is bound to JIP-1, it reduces JNK activation, leading to reduced phosphorylation of the JNK target c-Jun.	DISCUSS
40	43	JNK	protein_type	When MKP7 is bound to JIP-1, it reduces JNK activation, leading to reduced phosphorylation of the JNK target c-Jun.	DISCUSS
98	101	JNK	protein_type	When MKP7 is bound to JIP-1, it reduces JNK activation, leading to reduced phosphorylation of the JNK target c-Jun.	DISCUSS
109	114	c-Jun	protein_type	When MKP7 is bound to JIP-1, it reduces JNK activation, leading to reduced phosphorylation of the JNK target c-Jun.	DISCUSS
10	41	biochemical and structural data	evidence	Thus, our biochemical and structural data allow us to present a model for the JNK1–JIP-1–MKP7 ternary complex and provide an important insight into the assembly and function of JNK signalling modules (Supplementary Fig. 6).	DISCUSS
78	93	JNK1–JIP-1–MKP7	complex_assembly	Thus, our biochemical and structural data allow us to present a model for the JNK1–JIP-1–MKP7 ternary complex and provide an important insight into the assembly and function of JNK signalling modules (Supplementary Fig. 6).	DISCUSS
177	180	JNK	protein_type	Thus, our biochemical and structural data allow us to present a model for the JNK1–JIP-1–MKP7 ternary complex and provide an important insight into the assembly and function of JNK signalling modules (Supplementary Fig. 6).	DISCUSS
7	17	structures	evidence	Domain structures of ten human MKPs and the atypical VHR.	FIG
25	30	human	species	Domain structures of ten human MKPs and the atypical VHR.	FIG
31	35	MKPs	protein_type	Domain structures of ten human MKPs and the atypical VHR.	FIG
53	56	VHR	protein	Domain structures of ten human MKPs and the atypical VHR.	FIG
45	54	structure	evidence	On the basis of sequence similarity, protein structure, substrate specificity and subcellular localization, the ten members of MKP family can be divided into three groups.	FIG
127	137	MKP family	protein_type	On the basis of sequence similarity, protein structure, substrate specificity and subcellular localization, the ten members of MKP family can be divided into three groups.	FIG
30	34	MKP1	protein	The first subfamily comprises MKP1, MKP2, PAC1 and hVH3, which are inducible nuclear phosphatases and can dephosphorylate ERK (and JNK, p38) MAPKs.	FIG
36	40	MKP2	protein	The first subfamily comprises MKP1, MKP2, PAC1 and hVH3, which are inducible nuclear phosphatases and can dephosphorylate ERK (and JNK, p38) MAPKs.	FIG
42	46	PAC1	protein	The first subfamily comprises MKP1, MKP2, PAC1 and hVH3, which are inducible nuclear phosphatases and can dephosphorylate ERK (and JNK, p38) MAPKs.	FIG
51	55	hVH3	protein	The first subfamily comprises MKP1, MKP2, PAC1 and hVH3, which are inducible nuclear phosphatases and can dephosphorylate ERK (and JNK, p38) MAPKs.	FIG
67	76	inducible	protein_state	The first subfamily comprises MKP1, MKP2, PAC1 and hVH3, which are inducible nuclear phosphatases and can dephosphorylate ERK (and JNK, p38) MAPKs.	FIG
77	97	nuclear phosphatases	protein_type	The first subfamily comprises MKP1, MKP2, PAC1 and hVH3, which are inducible nuclear phosphatases and can dephosphorylate ERK (and JNK, p38) MAPKs.	FIG
122	125	ERK	protein_type	The first subfamily comprises MKP1, MKP2, PAC1 and hVH3, which are inducible nuclear phosphatases and can dephosphorylate ERK (and JNK, p38) MAPKs.	FIG
131	134	JNK	protein_type	The first subfamily comprises MKP1, MKP2, PAC1 and hVH3, which are inducible nuclear phosphatases and can dephosphorylate ERK (and JNK, p38) MAPKs.	FIG
136	139	p38	protein_type	The first subfamily comprises MKP1, MKP2, PAC1 and hVH3, which are inducible nuclear phosphatases and can dephosphorylate ERK (and JNK, p38) MAPKs.	FIG
141	146	MAPKs	protein_type	The first subfamily comprises MKP1, MKP2, PAC1 and hVH3, which are inducible nuclear phosphatases and can dephosphorylate ERK (and JNK, p38) MAPKs.	FIG
30	34	MKP3	protein	The second subfamily contains MKP3, MKP4 and MKPX, which are cytoplasmic ERK-specific MKPs.	FIG
36	40	MKP4	protein	The second subfamily contains MKP3, MKP4 and MKPX, which are cytoplasmic ERK-specific MKPs.	FIG
45	49	MKPX	protein	The second subfamily contains MKP3, MKP4 and MKPX, which are cytoplasmic ERK-specific MKPs.	FIG
73	90	ERK-specific MKPs	protein_type	The second subfamily contains MKP3, MKP4 and MKPX, which are cytoplasmic ERK-specific MKPs.	FIG
30	34	MKP5	protein	The third subfamily comprises MKP5, MKP7 and hVH5, which were located in both nucleus and cytoplasm, and selectively inactivate JNK and p38.	FIG
36	40	MKP7	protein	The third subfamily comprises MKP5, MKP7 and hVH5, which were located in both nucleus and cytoplasm, and selectively inactivate JNK and p38.	FIG
45	49	hVH5	protein	The third subfamily comprises MKP5, MKP7 and hVH5, which were located in both nucleus and cytoplasm, and selectively inactivate JNK and p38.	FIG
128	131	JNK	protein_type	The third subfamily comprises MKP5, MKP7 and hVH5, which were located in both nucleus and cytoplasm, and selectively inactivate JNK and p38.	FIG
136	139	p38	protein_type	The third subfamily comprises MKP5, MKP7 and hVH5, which were located in both nucleus and cytoplasm, and selectively inactivate JNK and p38.	FIG
4	8	MKPs	protein_type	All MKPs contain both the CD and KBD domains, whereas VHR, an atypical MKP, only contains a highly conserved catalytic domain.	FIG
26	28	CD	structure_element	All MKPs contain both the CD and KBD domains, whereas VHR, an atypical MKP, only contains a highly conserved catalytic domain.	FIG
33	36	KBD	structure_element	All MKPs contain both the CD and KBD domains, whereas VHR, an atypical MKP, only contains a highly conserved catalytic domain.	FIG
54	57	VHR	protein	All MKPs contain both the CD and KBD domains, whereas VHR, an atypical MKP, only contains a highly conserved catalytic domain.	FIG
71	74	MKP	protein_type	All MKPs contain both the CD and KBD domains, whereas VHR, an atypical MKP, only contains a highly conserved catalytic domain.	FIG
92	108	highly conserved	protein_state	All MKPs contain both the CD and KBD domains, whereas VHR, an atypical MKP, only contains a highly conserved catalytic domain.	FIG
109	125	catalytic domain	structure_element	All MKPs contain both the CD and KBD domains, whereas VHR, an atypical MKP, only contains a highly conserved catalytic domain.	FIG
19	21	CD	structure_element	In addition to the CD and KBD, MKP7 contains a unique long C-terminal region that contains NES, NLS and PEST motifs, which has no effect on the binding ability and phosphatase activity of MKP7 toward MAPKs.	FIG
26	29	KBD	structure_element	In addition to the CD and KBD, MKP7 contains a unique long C-terminal region that contains NES, NLS and PEST motifs, which has no effect on the binding ability and phosphatase activity of MKP7 toward MAPKs.	FIG
31	35	MKP7	protein	In addition to the CD and KBD, MKP7 contains a unique long C-terminal region that contains NES, NLS and PEST motifs, which has no effect on the binding ability and phosphatase activity of MKP7 toward MAPKs.	FIG
59	76	C-terminal region	structure_element	In addition to the CD and KBD, MKP7 contains a unique long C-terminal region that contains NES, NLS and PEST motifs, which has no effect on the binding ability and phosphatase activity of MKP7 toward MAPKs.	FIG
91	94	NES	structure_element	In addition to the CD and KBD, MKP7 contains a unique long C-terminal region that contains NES, NLS and PEST motifs, which has no effect on the binding ability and phosphatase activity of MKP7 toward MAPKs.	FIG
96	99	NLS	structure_element	In addition to the CD and KBD, MKP7 contains a unique long C-terminal region that contains NES, NLS and PEST motifs, which has no effect on the binding ability and phosphatase activity of MKP7 toward MAPKs.	FIG
104	115	PEST motifs	structure_element	In addition to the CD and KBD, MKP7 contains a unique long C-terminal region that contains NES, NLS and PEST motifs, which has no effect on the binding ability and phosphatase activity of MKP7 toward MAPKs.	FIG
188	192	MKP7	protein	In addition to the CD and KBD, MKP7 contains a unique long C-terminal region that contains NES, NLS and PEST motifs, which has no effect on the binding ability and phosphatase activity of MKP7 toward MAPKs.	FIG
200	205	MAPKs	protein_type	In addition to the CD and KBD, MKP7 contains a unique long C-terminal region that contains NES, NLS and PEST motifs, which has no effect on the binding ability and phosphatase activity of MKP7 toward MAPKs.	FIG
0	3	NES	structure_element	NES, nuclear export signal; NLS, nuclear localization signal; PEST, C-terminal sequence rich in prolines, glutamates, serines and threonines.	FIG
5	26	nuclear export signal	structure_element	NES, nuclear export signal; NLS, nuclear localization signal; PEST, C-terminal sequence rich in prolines, glutamates, serines and threonines.	FIG
28	31	NLS	structure_element	NES, nuclear export signal; NLS, nuclear localization signal; PEST, C-terminal sequence rich in prolines, glutamates, serines and threonines.	FIG
33	60	nuclear localization signal	structure_element	NES, nuclear export signal; NLS, nuclear localization signal; PEST, C-terminal sequence rich in prolines, glutamates, serines and threonines.	FIG
62	66	PEST	structure_element	NES, nuclear export signal; NLS, nuclear localization signal; PEST, C-terminal sequence rich in prolines, glutamates, serines and threonines.	FIG
68	92	C-terminal sequence rich	structure_element	NES, nuclear export signal; NLS, nuclear localization signal; PEST, C-terminal sequence rich in prolines, glutamates, serines and threonines.	FIG
96	104	prolines	residue_name	NES, nuclear export signal; NLS, nuclear localization signal; PEST, C-terminal sequence rich in prolines, glutamates, serines and threonines.	FIG
106	116	glutamates	residue_name	NES, nuclear export signal; NLS, nuclear localization signal; PEST, C-terminal sequence rich in prolines, glutamates, serines and threonines.	FIG
118	125	serines	residue_name	NES, nuclear export signal; NLS, nuclear localization signal; PEST, C-terminal sequence rich in prolines, glutamates, serines and threonines.	FIG
130	140	threonines	residue_name	NES, nuclear export signal; NLS, nuclear localization signal; PEST, C-terminal sequence rich in prolines, glutamates, serines and threonines.	FIG
0	4	MKP7	protein	MKP7-CD is crucial for JNK1 binding and enzyme catalysis.	FIG
5	7	CD	structure_element	MKP7-CD is crucial for JNK1 binding and enzyme catalysis.	FIG
23	27	JNK1	protein	MKP7-CD is crucial for JNK1 binding and enzyme catalysis.	FIG
27	32	human	species	(a) Domain organization of human MKP7 and JNK1.	FIG
33	37	MKP7	protein	(a) Domain organization of human MKP7 and JNK1.	FIG
42	46	JNK1	protein	(a) Domain organization of human MKP7 and JNK1.	FIG
4	7	KBD	structure_element	The KBD and CD of MKP7 are shown in green and blue, and the N-lobe and C-lobe of JNK1 are coloured in lemon and yellow, respectively.	FIG
12	14	CD	structure_element	The KBD and CD of MKP7 are shown in green and blue, and the N-lobe and C-lobe of JNK1 are coloured in lemon and yellow, respectively.	FIG
18	22	MKP7	protein	The KBD and CD of MKP7 are shown in green and blue, and the N-lobe and C-lobe of JNK1 are coloured in lemon and yellow, respectively.	FIG
60	66	N-lobe	structure_element	The KBD and CD of MKP7 are shown in green and blue, and the N-lobe and C-lobe of JNK1 are coloured in lemon and yellow, respectively.	FIG
71	77	C-lobe	structure_element	The KBD and CD of MKP7 are shown in green and blue, and the N-lobe and C-lobe of JNK1 are coloured in lemon and yellow, respectively.	FIG
81	85	JNK1	protein	The KBD and CD of MKP7 are shown in green and blue, and the N-lobe and C-lobe of JNK1 are coloured in lemon and yellow, respectively.	FIG
87	112	Plots of initial velocity	evidence	The colour scheme is the same in the following figures unless indicated otherwise. (b) Plots of initial velocity of the MKP7-catalysed reaction versus phospho-JNK1 concentration.	FIG
120	124	MKP7	protein	The colour scheme is the same in the following figures unless indicated otherwise. (b) Plots of initial velocity of the MKP7-catalysed reaction versus phospho-JNK1 concentration.	FIG
151	158	phospho	ptm	The colour scheme is the same in the following figures unless indicated otherwise. (b) Plots of initial velocity of the MKP7-catalysed reaction versus phospho-JNK1 concentration.	FIG
159	163	JNK1	protein	The colour scheme is the same in the following figures unless indicated otherwise. (b) Plots of initial velocity of the MKP7-catalysed reaction versus phospho-JNK1 concentration.	FIG
36	59	Gel filtration analysis	experimental_method	The error bars represent s.e.m. (c) Gel filtration analysis for interaction of JNK1 with MKP7-CD and MKP7-KBD.	FIG
79	83	JNK1	protein	The error bars represent s.e.m. (c) Gel filtration analysis for interaction of JNK1 with MKP7-CD and MKP7-KBD.	FIG
89	93	MKP7	protein	The error bars represent s.e.m. (c) Gel filtration analysis for interaction of JNK1 with MKP7-CD and MKP7-KBD.	FIG
94	96	CD	structure_element	The error bars represent s.e.m. (c) Gel filtration analysis for interaction of JNK1 with MKP7-CD and MKP7-KBD.	FIG
101	105	MKP7	protein	The error bars represent s.e.m. (c) Gel filtration analysis for interaction of JNK1 with MKP7-CD and MKP7-KBD.	FIG
106	109	KBD	structure_element	The error bars represent s.e.m. (c) Gel filtration analysis for interaction of JNK1 with MKP7-CD and MKP7-KBD.	FIG
4	32	GST-mediated pull-down assay	experimental_method	(d) GST-mediated pull-down assay for interaction of JNK1 with MKP7-CD and MKP7-KBD.	FIG
52	56	JNK1	protein	(d) GST-mediated pull-down assay for interaction of JNK1 with MKP7-CD and MKP7-KBD.	FIG
62	66	MKP7	protein	(d) GST-mediated pull-down assay for interaction of JNK1 with MKP7-CD and MKP7-KBD.	FIG
67	69	CD	structure_element	(d) GST-mediated pull-down assay for interaction of JNK1 with MKP7-CD and MKP7-KBD.	FIG
74	78	MKP7	protein	(d) GST-mediated pull-down assay for interaction of JNK1 with MKP7-CD and MKP7-KBD.	FIG
79	82	KBD	structure_element	(d) GST-mediated pull-down assay for interaction of JNK1 with MKP7-CD and MKP7-KBD.	FIG
33	43	affinities	evidence	The top panel shows the relative affinities of MKP7-CD and MKP7-KBD to JNK1, with the affinity of MKP7-CD defined as 100%; the middle panel is the electrophoretic pattern of MKP7 and JNK1 after GST pull-down assays.	FIG
47	51	MKP7	protein	The top panel shows the relative affinities of MKP7-CD and MKP7-KBD to JNK1, with the affinity of MKP7-CD defined as 100%; the middle panel is the electrophoretic pattern of MKP7 and JNK1 after GST pull-down assays.	FIG
52	54	CD	structure_element	The top panel shows the relative affinities of MKP7-CD and MKP7-KBD to JNK1, with the affinity of MKP7-CD defined as 100%; the middle panel is the electrophoretic pattern of MKP7 and JNK1 after GST pull-down assays.	FIG
59	63	MKP7	protein	The top panel shows the relative affinities of MKP7-CD and MKP7-KBD to JNK1, with the affinity of MKP7-CD defined as 100%; the middle panel is the electrophoretic pattern of MKP7 and JNK1 after GST pull-down assays.	FIG
64	67	KBD	structure_element	The top panel shows the relative affinities of MKP7-CD and MKP7-KBD to JNK1, with the affinity of MKP7-CD defined as 100%; the middle panel is the electrophoretic pattern of MKP7 and JNK1 after GST pull-down assays.	FIG
71	75	JNK1	protein	The top panel shows the relative affinities of MKP7-CD and MKP7-KBD to JNK1, with the affinity of MKP7-CD defined as 100%; the middle panel is the electrophoretic pattern of MKP7 and JNK1 after GST pull-down assays.	FIG
86	94	affinity	evidence	The top panel shows the relative affinities of MKP7-CD and MKP7-KBD to JNK1, with the affinity of MKP7-CD defined as 100%; the middle panel is the electrophoretic pattern of MKP7 and JNK1 after GST pull-down assays.	FIG
98	102	MKP7	protein	The top panel shows the relative affinities of MKP7-CD and MKP7-KBD to JNK1, with the affinity of MKP7-CD defined as 100%; the middle panel is the electrophoretic pattern of MKP7 and JNK1 after GST pull-down assays.	FIG
103	105	CD	structure_element	The top panel shows the relative affinities of MKP7-CD and MKP7-KBD to JNK1, with the affinity of MKP7-CD defined as 100%; the middle panel is the electrophoretic pattern of MKP7 and JNK1 after GST pull-down assays.	FIG
174	178	MKP7	protein	The top panel shows the relative affinities of MKP7-CD and MKP7-KBD to JNK1, with the affinity of MKP7-CD defined as 100%; the middle panel is the electrophoretic pattern of MKP7 and JNK1 after GST pull-down assays.	FIG
183	187	JNK1	protein	The top panel shows the relative affinities of MKP7-CD and MKP7-KBD to JNK1, with the affinity of MKP7-CD defined as 100%; the middle panel is the electrophoretic pattern of MKP7 and JNK1 after GST pull-down assays.	FIG
194	214	GST pull-down assays	experimental_method	The top panel shows the relative affinities of MKP7-CD and MKP7-KBD to JNK1, with the affinity of MKP7-CD defined as 100%; the middle panel is the electrophoretic pattern of MKP7 and JNK1 after GST pull-down assays.	FIG
23	27	MKP7	protein	The protein amounts of MKP7 used are shown at the bottom.	FIG
0	9	Structure	evidence	Structure of JNK1 in complex with MKP7-CD.	FIG
13	17	JNK1	protein	Structure of JNK1 in complex with MKP7-CD.	FIG
18	33	in complex with	protein_state	Structure of JNK1 in complex with MKP7-CD.	FIG
34	38	MKP7	protein	Structure of JNK1 in complex with MKP7-CD.	FIG
39	41	CD	structure_element	Structure of JNK1 in complex with MKP7-CD.	FIG
22	34	JNK1–MKP7-CD	complex_assembly	(a) Ribbon diagram of JNK1–MKP7-CD complex in two views related by a 45° rotation around a vertical axis. (b) Structure of MKP7-CD with its active site highlight in cyan.	FIG
110	119	Structure	evidence	(a) Ribbon diagram of JNK1–MKP7-CD complex in two views related by a 45° rotation around a vertical axis. (b) Structure of MKP7-CD with its active site highlight in cyan.	FIG
123	127	MKP7	protein	(a) Ribbon diagram of JNK1–MKP7-CD complex in two views related by a 45° rotation around a vertical axis. (b) Structure of MKP7-CD with its active site highlight in cyan.	FIG
128	130	CD	structure_element	(a) Ribbon diagram of JNK1–MKP7-CD complex in two views related by a 45° rotation around a vertical axis. (b) Structure of MKP7-CD with its active site highlight in cyan.	FIG
140	151	active site	site	(a) Ribbon diagram of JNK1–MKP7-CD complex in two views related by a 45° rotation around a vertical axis. (b) Structure of MKP7-CD with its active site highlight in cyan.	FIG
4	19	2Fo−Fc omit map	evidence	The 2Fo−Fc omit map (contoured at 1.5σ) for the P-loop of MKP7-CD is shown at inset of b. (c) Structure of VHR with its active site highlighted in marine blue. (d) Close-up view of the JNK1–MKP7 interface showing interacting amino acids of JNK1 (orange) and MKP7-CD (cyan).	FIG
48	54	P-loop	structure_element	The 2Fo−Fc omit map (contoured at 1.5σ) for the P-loop of MKP7-CD is shown at inset of b. (c) Structure of VHR with its active site highlighted in marine blue. (d) Close-up view of the JNK1–MKP7 interface showing interacting amino acids of JNK1 (orange) and MKP7-CD (cyan).	FIG
58	62	MKP7	protein	The 2Fo−Fc omit map (contoured at 1.5σ) for the P-loop of MKP7-CD is shown at inset of b. (c) Structure of VHR with its active site highlighted in marine blue. (d) Close-up view of the JNK1–MKP7 interface showing interacting amino acids of JNK1 (orange) and MKP7-CD (cyan).	FIG
63	65	CD	structure_element	The 2Fo−Fc omit map (contoured at 1.5σ) for the P-loop of MKP7-CD is shown at inset of b. (c) Structure of VHR with its active site highlighted in marine blue. (d) Close-up view of the JNK1–MKP7 interface showing interacting amino acids of JNK1 (orange) and MKP7-CD (cyan).	FIG
94	103	Structure	evidence	The 2Fo−Fc omit map (contoured at 1.5σ) for the P-loop of MKP7-CD is shown at inset of b. (c) Structure of VHR with its active site highlighted in marine blue. (d) Close-up view of the JNK1–MKP7 interface showing interacting amino acids of JNK1 (orange) and MKP7-CD (cyan).	FIG
107	110	VHR	protein	The 2Fo−Fc omit map (contoured at 1.5σ) for the P-loop of MKP7-CD is shown at inset of b. (c) Structure of VHR with its active site highlighted in marine blue. (d) Close-up view of the JNK1–MKP7 interface showing interacting amino acids of JNK1 (orange) and MKP7-CD (cyan).	FIG
120	131	active site	site	The 2Fo−Fc omit map (contoured at 1.5σ) for the P-loop of MKP7-CD is shown at inset of b. (c) Structure of VHR with its active site highlighted in marine blue. (d) Close-up view of the JNK1–MKP7 interface showing interacting amino acids of JNK1 (orange) and MKP7-CD (cyan).	FIG
185	204	JNK1–MKP7 interface	site	The 2Fo−Fc omit map (contoured at 1.5σ) for the P-loop of MKP7-CD is shown at inset of b. (c) Structure of VHR with its active site highlighted in marine blue. (d) Close-up view of the JNK1–MKP7 interface showing interacting amino acids of JNK1 (orange) and MKP7-CD (cyan).	FIG
240	244	JNK1	protein	The 2Fo−Fc omit map (contoured at 1.5σ) for the P-loop of MKP7-CD is shown at inset of b. (c) Structure of VHR with its active site highlighted in marine blue. (d) Close-up view of the JNK1–MKP7 interface showing interacting amino acids of JNK1 (orange) and MKP7-CD (cyan).	FIG
258	262	MKP7	protein	The 2Fo−Fc omit map (contoured at 1.5σ) for the P-loop of MKP7-CD is shown at inset of b. (c) Structure of VHR with its active site highlighted in marine blue. (d) Close-up view of the JNK1–MKP7 interface showing interacting amino acids of JNK1 (orange) and MKP7-CD (cyan).	FIG
263	265	CD	structure_element	The 2Fo−Fc omit map (contoured at 1.5σ) for the P-loop of MKP7-CD is shown at inset of b. (c) Structure of VHR with its active site highlighted in marine blue. (d) Close-up view of the JNK1–MKP7 interface showing interacting amino acids of JNK1 (orange) and MKP7-CD (cyan).	FIG
4	8	JNK1	protein	The JNK1 is shown in surface representation coloured according to electrostatic potential (positive, blue; negative, red).	FIG
4	24	Interaction networks	site	(e) Interaction networks mainly involving helices α4 and α5 from MKP7-CD, and αG and α2L14 of JNK1.	FIG
42	49	helices	structure_element	(e) Interaction networks mainly involving helices α4 and α5 from MKP7-CD, and αG and α2L14 of JNK1.	FIG
50	52	α4	structure_element	(e) Interaction networks mainly involving helices α4 and α5 from MKP7-CD, and αG and α2L14 of JNK1.	FIG
57	59	α5	structure_element	(e) Interaction networks mainly involving helices α4 and α5 from MKP7-CD, and αG and α2L14 of JNK1.	FIG
65	69	MKP7	protein	(e) Interaction networks mainly involving helices α4 and α5 from MKP7-CD, and αG and α2L14 of JNK1.	FIG
70	72	CD	structure_element	(e) Interaction networks mainly involving helices α4 and α5 from MKP7-CD, and αG and α2L14 of JNK1.	FIG
78	80	αG	structure_element	(e) Interaction networks mainly involving helices α4 and α5 from MKP7-CD, and αG and α2L14 of JNK1.	FIG
85	90	α2L14	structure_element	(e) Interaction networks mainly involving helices α4 and α5 from MKP7-CD, and αG and α2L14 of JNK1.	FIG
94	98	JNK1	protein	(e) Interaction networks mainly involving helices α4 and α5 from MKP7-CD, and αG and α2L14 of JNK1.	FIG
0	4	MKP7	protein	MKP7-CD is shown in surface representation coloured according to electrostatic potential (positive, blue; negative, red).	FIG
5	7	CD	structure_element	MKP7-CD is shown in surface representation coloured according to electrostatic potential (positive, blue; negative, red).	FIG
28	46	polar interactions	bond_interaction	Blue dashed lines represent polar interactions.	FIG
28	46	polar interactions	bond_interaction	Blue dashed lines represent polar interactions.	FIG
8	23	2Fo−Fc omit map	evidence	(f) The 2Fo−Fc omit map (contoured at 1.5σ) clearly shows electron density for the 285FNFL288 segment of MKP7-CD.	FIG
58	74	electron density	evidence	(f) The 2Fo−Fc omit map (contoured at 1.5σ) clearly shows electron density for the 285FNFL288 segment of MKP7-CD.	FIG
83	101	285FNFL288 segment	structure_element	(f) The 2Fo−Fc omit map (contoured at 1.5σ) clearly shows electron density for the 285FNFL288 segment of MKP7-CD.	FIG
105	109	MKP7	protein	(f) The 2Fo−Fc omit map (contoured at 1.5σ) clearly shows electron density for the 285FNFL288 segment of MKP7-CD.	FIG
110	112	CD	structure_element	(f) The 2Fo−Fc omit map (contoured at 1.5σ) clearly shows electron density for the 285FNFL288 segment of MKP7-CD.	FIG
0	19	Mutational analysis	experimental_method	Mutational analysis on interactions between MKP7-CD and JNK1.	FIG
44	48	MKP7	protein	Mutational analysis on interactions between MKP7-CD and JNK1.	FIG
49	51	CD	structure_element	Mutational analysis on interactions between MKP7-CD and JNK1.	FIG
56	60	JNK1	protein	Mutational analysis on interactions between MKP7-CD and JNK1.	FIG
28	32	MKP7	protein	(a) Effects of mutations in MKP7-CD on the JNK1 dephosphorylation (mean±s.e.m., n=3).	FIG
33	35	CD	structure_element	(a) Effects of mutations in MKP7-CD on the JNK1 dephosphorylation (mean±s.e.m., n=3).	FIG
43	47	JNK1	protein	(a) Effects of mutations in MKP7-CD on the JNK1 dephosphorylation (mean±s.e.m., n=3).	FIG
48	65	dephosphorylation	ptm	(a) Effects of mutations in MKP7-CD on the JNK1 dephosphorylation (mean±s.e.m., n=3).	FIG
21	57	hydrophobic and hydrophilic contacts	bond_interaction	Residues involved in hydrophobic and hydrophilic contacts are coloured in red and blue, respectively. (b) Gel filtration analysis for interaction of JNK1 with MKP7-CD mutant F285D.	FIG
106	129	Gel filtration analysis	experimental_method	Residues involved in hydrophobic and hydrophilic contacts are coloured in red and blue, respectively. (b) Gel filtration analysis for interaction of JNK1 with MKP7-CD mutant F285D.	FIG
149	153	JNK1	protein	Residues involved in hydrophobic and hydrophilic contacts are coloured in red and blue, respectively. (b) Gel filtration analysis for interaction of JNK1 with MKP7-CD mutant F285D.	FIG
159	163	MKP7	protein	Residues involved in hydrophobic and hydrophilic contacts are coloured in red and blue, respectively. (b) Gel filtration analysis for interaction of JNK1 with MKP7-CD mutant F285D.	FIG
164	166	CD	structure_element	Residues involved in hydrophobic and hydrophilic contacts are coloured in red and blue, respectively. (b) Gel filtration analysis for interaction of JNK1 with MKP7-CD mutant F285D.	FIG
167	173	mutant	protein_state	Residues involved in hydrophobic and hydrophilic contacts are coloured in red and blue, respectively. (b) Gel filtration analysis for interaction of JNK1 with MKP7-CD mutant F285D.	FIG
174	179	F285D	mutant	Residues involved in hydrophobic and hydrophilic contacts are coloured in red and blue, respectively. (b) Gel filtration analysis for interaction of JNK1 with MKP7-CD mutant F285D.	FIG
0	6	Mutant	protein_state	Mutant F285D and JNK1 were eluted as monomers, with the molecular masses of ∼17 and 44 kDa, respectively.	FIG
7	12	F285D	mutant	Mutant F285D and JNK1 were eluted as monomers, with the molecular masses of ∼17 and 44 kDa, respectively.	FIG
17	21	JNK1	protein	Mutant F285D and JNK1 were eluted as monomers, with the molecular masses of ∼17 and 44 kDa, respectively.	FIG
37	45	monomers	oligomeric_state	Mutant F285D and JNK1 were eluted as monomers, with the molecular masses of ∼17 and 44 kDa, respectively.	FIG
28	37	wild-type	protein_state	However, in contrast to the wild-type MKP7-CD, mutant F285D did not co-migrate with JNK1.	FIG
38	42	MKP7	protein	However, in contrast to the wild-type MKP7-CD, mutant F285D did not co-migrate with JNK1.	FIG
43	45	CD	structure_element	However, in contrast to the wild-type MKP7-CD, mutant F285D did not co-migrate with JNK1.	FIG
47	53	mutant	protein_state	However, in contrast to the wild-type MKP7-CD, mutant F285D did not co-migrate with JNK1.	FIG
54	59	F285D	mutant	However, in contrast to the wild-type MKP7-CD, mutant F285D did not co-migrate with JNK1.	FIG
84	88	JNK1	protein	However, in contrast to the wild-type MKP7-CD, mutant F285D did not co-migrate with JNK1.	FIG
4	20	Pull-down assays	experimental_method	(c) Pull-down assays of MKP7-CD by GST-tagged JNK1 mutants.	FIG
24	28	MKP7	protein	(c) Pull-down assays of MKP7-CD by GST-tagged JNK1 mutants.	FIG
29	31	CD	structure_element	(c) Pull-down assays of MKP7-CD by GST-tagged JNK1 mutants.	FIG
35	45	GST-tagged	protein_state	(c) Pull-down assays of MKP7-CD by GST-tagged JNK1 mutants.	FIG
46	50	JNK1	protein	(c) Pull-down assays of MKP7-CD by GST-tagged JNK1 mutants.	FIG
51	58	mutants	protein_state	(c) Pull-down assays of MKP7-CD by GST-tagged JNK1 mutants.	FIG
33	43	affinities	evidence	The top panel shows the relative affinities of MKP7-CD to JNK1 mutants, with the affinity of wild-type JNK1 defined as 100%, the middle panel is the electrophoretic pattern of MKP7-CD and JNK1 mutants after GST pull-down assays.	FIG
47	51	MKP7	protein	The top panel shows the relative affinities of MKP7-CD to JNK1 mutants, with the affinity of wild-type JNK1 defined as 100%, the middle panel is the electrophoretic pattern of MKP7-CD and JNK1 mutants after GST pull-down assays.	FIG
52	54	CD	structure_element	The top panel shows the relative affinities of MKP7-CD to JNK1 mutants, with the affinity of wild-type JNK1 defined as 100%, the middle panel is the electrophoretic pattern of MKP7-CD and JNK1 mutants after GST pull-down assays.	FIG
58	62	JNK1	protein	The top panel shows the relative affinities of MKP7-CD to JNK1 mutants, with the affinity of wild-type JNK1 defined as 100%, the middle panel is the electrophoretic pattern of MKP7-CD and JNK1 mutants after GST pull-down assays.	FIG
63	70	mutants	protein_state	The top panel shows the relative affinities of MKP7-CD to JNK1 mutants, with the affinity of wild-type JNK1 defined as 100%, the middle panel is the electrophoretic pattern of MKP7-CD and JNK1 mutants after GST pull-down assays.	FIG
81	89	affinity	evidence	The top panel shows the relative affinities of MKP7-CD to JNK1 mutants, with the affinity of wild-type JNK1 defined as 100%, the middle panel is the electrophoretic pattern of MKP7-CD and JNK1 mutants after GST pull-down assays.	FIG
93	102	wild-type	protein_state	The top panel shows the relative affinities of MKP7-CD to JNK1 mutants, with the affinity of wild-type JNK1 defined as 100%, the middle panel is the electrophoretic pattern of MKP7-CD and JNK1 mutants after GST pull-down assays.	FIG
103	107	JNK1	protein	The top panel shows the relative affinities of MKP7-CD to JNK1 mutants, with the affinity of wild-type JNK1 defined as 100%, the middle panel is the electrophoretic pattern of MKP7-CD and JNK1 mutants after GST pull-down assays.	FIG
176	180	MKP7	protein	The top panel shows the relative affinities of MKP7-CD to JNK1 mutants, with the affinity of wild-type JNK1 defined as 100%, the middle panel is the electrophoretic pattern of MKP7-CD and JNK1 mutants after GST pull-down assays.	FIG
181	183	CD	structure_element	The top panel shows the relative affinities of MKP7-CD to JNK1 mutants, with the affinity of wild-type JNK1 defined as 100%, the middle panel is the electrophoretic pattern of MKP7-CD and JNK1 mutants after GST pull-down assays.	FIG
188	192	JNK1	protein	The top panel shows the relative affinities of MKP7-CD to JNK1 mutants, with the affinity of wild-type JNK1 defined as 100%, the middle panel is the electrophoretic pattern of MKP7-CD and JNK1 mutants after GST pull-down assays.	FIG
193	200	mutants	protein_state	The top panel shows the relative affinities of MKP7-CD to JNK1 mutants, with the affinity of wild-type JNK1 defined as 100%, the middle panel is the electrophoretic pattern of MKP7-CD and JNK1 mutants after GST pull-down assays.	FIG
207	227	GST pull-down assays	experimental_method	The top panel shows the relative affinities of MKP7-CD to JNK1 mutants, with the affinity of wild-type JNK1 defined as 100%, the middle panel is the electrophoretic pattern of MKP7-CD and JNK1 mutants after GST pull-down assays.	FIG
23	27	MKP7	protein	The protein amounts of MKP7-CD used are shown at the bottom. (d) Circular dichroism spectra for MKP7-CD wild type and mutants.	FIG
28	30	CD	structure_element	The protein amounts of MKP7-CD used are shown at the bottom. (d) Circular dichroism spectra for MKP7-CD wild type and mutants.	FIG
65	83	Circular dichroism	experimental_method	The protein amounts of MKP7-CD used are shown at the bottom. (d) Circular dichroism spectra for MKP7-CD wild type and mutants.	FIG
84	91	spectra	evidence	The protein amounts of MKP7-CD used are shown at the bottom. (d) Circular dichroism spectra for MKP7-CD wild type and mutants.	FIG
96	100	MKP7	protein	The protein amounts of MKP7-CD used are shown at the bottom. (d) Circular dichroism spectra for MKP7-CD wild type and mutants.	FIG
101	103	CD	structure_element	The protein amounts of MKP7-CD used are shown at the bottom. (d) Circular dichroism spectra for MKP7-CD wild type and mutants.	FIG
104	113	wild type	protein_state	The protein amounts of MKP7-CD used are shown at the bottom. (d) Circular dichroism spectra for MKP7-CD wild type and mutants.	FIG
118	125	mutants	protein_state	The protein amounts of MKP7-CD used are shown at the bottom. (d) Circular dichroism spectra for MKP7-CD wild type and mutants.	FIG
48	66	Circular dichroism	experimental_method	Measurements were averaged for three scans. (e) Circular dichroism spectra for JNK1 wild type and mutants.	FIG
67	74	spectra	evidence	Measurements were averaged for three scans. (e) Circular dichroism spectra for JNK1 wild type and mutants.	FIG
79	83	JNK1	protein	Measurements were averaged for three scans. (e) Circular dichroism spectra for JNK1 wild type and mutants.	FIG
84	93	wild type	protein_state	Measurements were averaged for three scans. (e) Circular dichroism spectra for JNK1 wild type and mutants.	FIG
98	105	mutants	protein_state	Measurements were averaged for three scans. (e) Circular dichroism spectra for JNK1 wild type and mutants.	FIG
15	24	mutations	experimental_method	(f) Effects of mutations in MKP7-CD on the pNPP hydrolysis reaction (mean±s.e.m., n=3).	FIG
28	32	MKP7	protein	(f) Effects of mutations in MKP7-CD on the pNPP hydrolysis reaction (mean±s.e.m., n=3).	FIG
33	35	CD	structure_element	(f) Effects of mutations in MKP7-CD on the pNPP hydrolysis reaction (mean±s.e.m., n=3).	FIG
43	47	pNPP	chemical	(f) Effects of mutations in MKP7-CD on the pNPP hydrolysis reaction (mean±s.e.m., n=3).	FIG
14	22	CDK2-KAP	complex_assembly	Comparison of CDK2-KAP and JNK1–MKP7-CD.	FIG
27	39	JNK1–MKP7-CD	complex_assembly	Comparison of CDK2-KAP and JNK1–MKP7-CD.	FIG
4	17	Superposition	experimental_method	(a) Superposition of the complex structures of CDK2-KAP (PDB 1FQ1) and JNK1–MKP7-CD.	FIG
33	43	structures	evidence	(a) Superposition of the complex structures of CDK2-KAP (PDB 1FQ1) and JNK1–MKP7-CD.	FIG
47	55	CDK2-KAP	complex_assembly	(a) Superposition of the complex structures of CDK2-KAP (PDB 1FQ1) and JNK1–MKP7-CD.	FIG
71	83	JNK1–MKP7-CD	complex_assembly	(a) Superposition of the complex structures of CDK2-KAP (PDB 1FQ1) and JNK1–MKP7-CD.	FIG
4	10	N-lobe	structure_element	The N-lobe and C-lobe of CDK2 are coloured in grey and pink, respectively, and KAP is coloured in green.	FIG
15	21	C-lobe	structure_element	The N-lobe and C-lobe of CDK2 are coloured in grey and pink, respectively, and KAP is coloured in green.	FIG
25	29	CDK2	protein	The N-lobe and C-lobe of CDK2 are coloured in grey and pink, respectively, and KAP is coloured in green.	FIG
79	82	KAP	protein	The N-lobe and C-lobe of CDK2 are coloured in grey and pink, respectively, and KAP is coloured in green.	FIG
75	90	contact regions	site	The interactions between these two proteins consist of three discontinuous contact regions, centred at the multiple hydrogen bonds between the pThr160 of CDK2 and the active site of KAP (region I).	FIG
116	130	hydrogen bonds	bond_interaction	The interactions between these two proteins consist of three discontinuous contact regions, centred at the multiple hydrogen bonds between the pThr160 of CDK2 and the active site of KAP (region I).	FIG
143	150	pThr160	ptm	The interactions between these two proteins consist of three discontinuous contact regions, centred at the multiple hydrogen bonds between the pThr160 of CDK2 and the active site of KAP (region I).	FIG
154	158	CDK2	protein	The interactions between these two proteins consist of three discontinuous contact regions, centred at the multiple hydrogen bonds between the pThr160 of CDK2 and the active site of KAP (region I).	FIG
167	178	active site	site	The interactions between these two proteins consist of three discontinuous contact regions, centred at the multiple hydrogen bonds between the pThr160 of CDK2 and the active site of KAP (region I).	FIG
182	185	KAP	protein	The interactions between these two proteins consist of three discontinuous contact regions, centred at the multiple hydrogen bonds between the pThr160 of CDK2 and the active site of KAP (region I).	FIG
187	195	region I	structure_element	The interactions between these two proteins consist of three discontinuous contact regions, centred at the multiple hydrogen bonds between the pThr160 of CDK2 and the active site of KAP (region I).	FIG
34	38	CDK2	protein	Interestingly, the recognition of CDK2 by KAP is augmented by a similar interface as that observed in the complex of JNK1 and MKP7-CD (region II).	FIG
42	45	KAP	protein	Interestingly, the recognition of CDK2 by KAP is augmented by a similar interface as that observed in the complex of JNK1 and MKP7-CD (region II).	FIG
72	81	interface	site	Interestingly, the recognition of CDK2 by KAP is augmented by a similar interface as that observed in the complex of JNK1 and MKP7-CD (region II).	FIG
117	121	JNK1	protein	Interestingly, the recognition of CDK2 by KAP is augmented by a similar interface as that observed in the complex of JNK1 and MKP7-CD (region II).	FIG
126	130	MKP7	protein	Interestingly, the recognition of CDK2 by KAP is augmented by a similar interface as that observed in the complex of JNK1 and MKP7-CD (region II).	FIG
131	133	CD	structure_element	Interestingly, the recognition of CDK2 by KAP is augmented by a similar interface as that observed in the complex of JNK1 and MKP7-CD (region II).	FIG
135	144	region II	structure_element	Interestingly, the recognition of CDK2 by KAP is augmented by a similar interface as that observed in the complex of JNK1 and MKP7-CD (region II).	FIG
33	52	auxiliary region II	structure_element	(b) Interactions networks at the auxiliary region II mainly involving helix α7 from KAP and the αG helix and following L14 loop of CDK2.	FIG
70	75	helix	structure_element	(b) Interactions networks at the auxiliary region II mainly involving helix α7 from KAP and the αG helix and following L14 loop of CDK2.	FIG
76	78	α7	structure_element	(b) Interactions networks at the auxiliary region II mainly involving helix α7 from KAP and the αG helix and following L14 loop of CDK2.	FIG
84	87	KAP	protein	(b) Interactions networks at the auxiliary region II mainly involving helix α7 from KAP and the αG helix and following L14 loop of CDK2.	FIG
96	104	αG helix	structure_element	(b) Interactions networks at the auxiliary region II mainly involving helix α7 from KAP and the αG helix and following L14 loop of CDK2.	FIG
119	127	L14 loop	structure_element	(b) Interactions networks at the auxiliary region II mainly involving helix α7 from KAP and the αG helix and following L14 loop of CDK2.	FIG
131	135	CDK2	protein	(b) Interactions networks at the auxiliary region II mainly involving helix α7 from KAP and the αG helix and following L14 loop of CDK2.	FIG
4	8	CDK2	protein	The CDK2 is shown in surface representation coloured according to the electrostatic potential (positive, blue; negative, red).	FIG
12	15	KAP	protein	Residues of KAP and CDK2 are highlighted as green and red sticks, respectively.	FIG
20	24	CDK2	protein	Residues of KAP and CDK2 are highlighted as green and red sticks, respectively.	FIG
81	86	helix	structure_element	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
87	89	α6	structure_element	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
93	96	KAP	protein	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
115	120	helix	structure_element	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
121	123	α4	structure_element	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
127	131	MKP7	protein	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
132	134	CD	structure_element	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
185	191	stable	protein_state	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
192	203	heterodimer	oligomeric_state	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
207	211	CDK2	protein	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
216	219	KAP	protein	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
225	243	Sequence alignment	experimental_method	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
251	274	JNK-interacting regions	site	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
278	282	MKPs	protein_type	One remarkable difference between these two kinase-phosphatase complexes is that helix α6 of KAP (corresponding to helix α4 of MKP7-CD) plays little, if any, role in the formation of a stable heterodimer of CDK2 and KAP. (c) Sequence alignment of the JNK-interacting regions on MKPs.	FIG
12	16	MKP7	protein	Residues of MKP7-CD involved in JNK1 recognition are indicated by cyan asterisks, and the conserved FXF-motif is highlighted in cyan.	FIG
17	19	CD	structure_element	Residues of MKP7-CD involved in JNK1 recognition are indicated by cyan asterisks, and the conserved FXF-motif is highlighted in cyan.	FIG
32	36	JNK1	protein	Residues of MKP7-CD involved in JNK1 recognition are indicated by cyan asterisks, and the conserved FXF-motif is highlighted in cyan.	FIG
90	99	conserved	protein_state	Residues of MKP7-CD involved in JNK1 recognition are indicated by cyan asterisks, and the conserved FXF-motif is highlighted in cyan.	FIG
100	109	FXF-motif	structure_element	Residues of MKP7-CD involved in JNK1 recognition are indicated by cyan asterisks, and the conserved FXF-motif is highlighted in cyan.	FIG
39	43	MKP7	protein	The secondary structure assignments of MKP7-CD and KAP are shown above and below each sequence.	FIG
44	46	CD	structure_element	The secondary structure assignments of MKP7-CD and KAP are shown above and below each sequence.	FIG
51	54	KAP	protein	The secondary structure assignments of MKP7-CD and KAP are shown above and below each sequence.	FIG
4	22	Sequence alignment	experimental_method	(d) Sequence alignment of the F-site regions on MAPKs.	FIG
30	44	F-site regions	structure_element	(d) Sequence alignment of the F-site regions on MAPKs.	FIG
48	53	MAPKs	protein_type	(d) Sequence alignment of the F-site regions on MAPKs.	FIG
12	16	JNK1	protein	Residues of JNK1 involved in recognition of MKP7 are indicated by orange asterisks, and those forming the F-site are highlighted in yellow.	FIG
44	48	MKP7	protein	Residues of JNK1 involved in recognition of MKP7 are indicated by orange asterisks, and those forming the F-site are highlighted in yellow.	FIG
106	112	F-site	site	Residues of JNK1 involved in recognition of MKP7 are indicated by orange asterisks, and those forming the F-site are highlighted in yellow.	FIG
0	9	FXF-motif	structure_element	FXF-motif is critical for controlling the phosphorylation of JNK and ultraviolet-induced apoptosis.	FIG
42	57	phosphorylation	ptm	FXF-motif is critical for controlling the phosphorylation of JNK and ultraviolet-induced apoptosis.	FIG
61	64	JNK	protein_type	FXF-motif is critical for controlling the phosphorylation of JNK and ultraviolet-induced apoptosis.	FIG
6	15	FXF-motif	structure_element	(a–c) FXF-motif is essential for the dephosphorylation of JNK by MKP7.	FIG
58	61	JNK	protein_type	(a–c) FXF-motif is essential for the dephosphorylation of JNK by MKP7.	FIG
65	69	MKP7	protein	(a–c) FXF-motif is essential for the dephosphorylation of JNK by MKP7.	FIG
33	45	lentiviruses	taxonomy_domain	HEK293T cells were infected with lentiviruses expressing MKP7 and its mutants (1.0 μg).	FIG
57	61	MKP7	protein	HEK293T cells were infected with lentiviruses expressing MKP7 and its mutants (1.0 μg).	FIG
70	77	mutants	protein_state	HEK293T cells were infected with lentiviruses expressing MKP7 and its mutants (1.0 μg).	FIG
71	80	etoposide	chemical	After 36 h infection, cells were untreated in a, stimulated with 30 μM etoposide for 3 h in b or irradiated with 25 J m−2 ultraviolet light at 30 min before lysis in c. Whole-cell extracts were then immunoblotted with antibody indicated.	FIG
34	48	phosphorylated	protein_state	Shown is a typical immunoblot for phosphorylated JNK from three independent experiments.	FIG
49	52	JNK	protein_type	Shown is a typical immunoblot for phosphorylated JNK from three independent experiments.	FIG
4	10	F-site	site	(d) F-site is required for JNK1 to interact with MKP7.	FIG
27	31	JNK1	protein	(d) F-site is required for JNK1 to interact with MKP7.	FIG
49	53	MKP7	protein	(d) F-site is required for JNK1 to interact with MKP7.	FIG
19	33	co-transfected	experimental_method	HEK293T cells were co-transfected with MKP7 full-length (1.0 μg) and JNK1 (wild type or mutants as indicated, 1.0 μg).	FIG
39	43	MKP7	protein	HEK293T cells were co-transfected with MKP7 full-length (1.0 μg) and JNK1 (wild type or mutants as indicated, 1.0 μg).	FIG
44	55	full-length	protein_state	HEK293T cells were co-transfected with MKP7 full-length (1.0 μg) and JNK1 (wild type or mutants as indicated, 1.0 μg).	FIG
69	73	JNK1	protein	HEK293T cells were co-transfected with MKP7 full-length (1.0 μg) and JNK1 (wild type or mutants as indicated, 1.0 μg).	FIG
75	84	wild type	protein_state	HEK293T cells were co-transfected with MKP7 full-length (1.0 μg) and JNK1 (wild type or mutants as indicated, 1.0 μg).	FIG
88	95	mutants	protein_state	HEK293T cells were co-transfected with MKP7 full-length (1.0 μg) and JNK1 (wild type or mutants as indicated, 1.0 μg).	FIG
30	48	immunoprecipitated	experimental_method	Whole-cell extracts were then immunoprecipitated with antibody against Myc for MKP7; immunobloting was carried out with antibodies indicated.	FIG
79	83	MKP7	protein	Whole-cell extracts were then immunoprecipitated with antibody against Myc for MKP7; immunobloting was carried out with antibodies indicated.	FIG
0	2	IP	experimental_method	IP, immunoprecipitation; TCL, total cell lysate.	FIG
4	23	immunoprecipitation	experimental_method	IP, immunoprecipitation; TCL, total cell lysate.	FIG
14	18	MKP7	protein	(e) Effect of MKP7 (wild type or mutants) expression on ultraviolet-induced apoptosis.	FIG
20	29	wild type	protein_state	(e) Effect of MKP7 (wild type or mutants) expression on ultraviolet-induced apoptosis.	FIG
33	40	mutants	protein_state	(e) Effect of MKP7 (wild type or mutants) expression on ultraviolet-induced apoptosis.	FIG
30	42	lentiviruses	taxonomy_domain	HeLa cells were infected with lentiviruses expressing MKP7 full-length and its mutants.	FIG
54	58	MKP7	protein	HeLa cells were infected with lentiviruses expressing MKP7 full-length and its mutants.	FIG
59	70	full-length	protein_state	HeLa cells were infected with lentiviruses expressing MKP7 full-length and its mutants.	FIG
79	86	mutants	protein_state	HeLa cells were infected with lentiviruses expressing MKP7 full-length and its mutants.	FIG
29	43	flow cytometry	experimental_method	Cells were then subjected to flow cytometry analysis.	FIG
35	48	Annexin-V-APC	chemical	Apoptotic cells were determined by Annexin-V-APC/PI staining.	FIG
49	51	PI	chemical	Apoptotic cells were determined by Annexin-V-APC/PI staining.	FIG
18	27	Annexin-V	chemical	The results using Annexin-V stain for membrane phosphatidylserine eversion, combined with propidium iodide (PI) uptake to evaluate cells whose membranes had been compromised.	FIG
90	106	propidium iodide	chemical	The results using Annexin-V stain for membrane phosphatidylserine eversion, combined with propidium iodide (PI) uptake to evaluate cells whose membranes had been compromised.	FIG
108	110	PI	chemical	The results using Annexin-V stain for membrane phosphatidylserine eversion, combined with propidium iodide (PI) uptake to evaluate cells whose membranes had been compromised.	FIG
19	28	Annexin-V	chemical	Staining with both Annexin-V and PI indicate apoptosis (upper right quadrant).	FIG
33	35	PI	chemical	Staining with both Annexin-V and PI indicate apoptosis (upper right quadrant).	FIG
64	66	*P	evidence	(f) Statistical analysis of apoptotic cells (mean±s.e.m., n=3), *P<0.05, ***P<0.001 (ANOVA followed by Tukey's test).	FIG
73	77	***P	evidence	(f) Statistical analysis of apoptotic cells (mean±s.e.m., n=3), *P<0.05, ***P<0.001 (ANOVA followed by Tukey's test).	FIG
85	90	ANOVA	experimental_method	(f) Statistical analysis of apoptotic cells (mean±s.e.m., n=3), *P<0.05, ***P<0.001 (ANOVA followed by Tukey's test).	FIG
103	115	Tukey's test	experimental_method	(f) Statistical analysis of apoptotic cells (mean±s.e.m., n=3), *P<0.05, ***P<0.001 (ANOVA followed by Tukey's test).	FIG
0	4	MKP5	protein	MKP5-CD is crucial for JNK1 binding and enzyme catalysis.	FIG
5	7	CD	structure_element	MKP5-CD is crucial for JNK1 binding and enzyme catalysis.	FIG
23	27	JNK1	protein	MKP5-CD is crucial for JNK1 binding and enzyme catalysis.	FIG
27	32	human	species	(a) Domain organization of human MKP5.	FIG
33	37	MKP5	protein	(a) Domain organization of human MKP5.	FIG
4	7	KBD	structure_element	The KBD and CD of MKP5 are shown in brown and grey, respectively. (b) Plots of initial velocity of the MKP5-catalysed reaction versus phospho-JNK1 concentration.	FIG
12	14	CD	structure_element	The KBD and CD of MKP5 are shown in brown and grey, respectively. (b) Plots of initial velocity of the MKP5-catalysed reaction versus phospho-JNK1 concentration.	FIG
18	22	MKP5	protein	The KBD and CD of MKP5 are shown in brown and grey, respectively. (b) Plots of initial velocity of the MKP5-catalysed reaction versus phospho-JNK1 concentration.	FIG
70	95	Plots of initial velocity	evidence	The KBD and CD of MKP5 are shown in brown and grey, respectively. (b) Plots of initial velocity of the MKP5-catalysed reaction versus phospho-JNK1 concentration.	FIG
103	107	MKP5	protein	The KBD and CD of MKP5 are shown in brown and grey, respectively. (b) Plots of initial velocity of the MKP5-catalysed reaction versus phospho-JNK1 concentration.	FIG
134	141	phospho	protein_state	The KBD and CD of MKP5 are shown in brown and grey, respectively. (b) Plots of initial velocity of the MKP5-catalysed reaction versus phospho-JNK1 concentration.	FIG
142	146	JNK1	protein	The KBD and CD of MKP5 are shown in brown and grey, respectively. (b) Plots of initial velocity of the MKP5-catalysed reaction versus phospho-JNK1 concentration.	FIG
89	91	Km	evidence	The solid lines are best-fitting results according to the Michaelis–Menten equation with Km and kcat values indicated.	FIG
96	100	kcat	evidence	The solid lines are best-fitting results according to the Michaelis–Menten equation with Km and kcat values indicated.	FIG
36	57	Structural comparison	experimental_method	The error bars represent s.e.m. (c) Structural comparison of the JNK-interacting residues on MKP5-CD (PDB 1ZZW) and MKP7-CD.	FIG
65	89	JNK-interacting residues	site	The error bars represent s.e.m. (c) Structural comparison of the JNK-interacting residues on MKP5-CD (PDB 1ZZW) and MKP7-CD.	FIG
93	97	MKP5	protein	The error bars represent s.e.m. (c) Structural comparison of the JNK-interacting residues on MKP5-CD (PDB 1ZZW) and MKP7-CD.	FIG
98	100	CD	structure_element	The error bars represent s.e.m. (c) Structural comparison of the JNK-interacting residues on MKP5-CD (PDB 1ZZW) and MKP7-CD.	FIG
116	120	MKP7	protein	The error bars represent s.e.m. (c) Structural comparison of the JNK-interacting residues on MKP5-CD (PDB 1ZZW) and MKP7-CD.	FIG
121	123	CD	structure_element	The error bars represent s.e.m. (c) Structural comparison of the JNK-interacting residues on MKP5-CD (PDB 1ZZW) and MKP7-CD.	FIG
30	34	MKP5	protein	The corresponding residues on MKP5 are depicted as orange sticks, and MKP5 residues numbers are in parentheses.	FIG
70	74	MKP5	protein	The corresponding residues on MKP5 are depicted as orange sticks, and MKP5 residues numbers are in parentheses.	FIG
4	27	Gel filtration analysis	experimental_method	(d) Gel filtration analysis for interaction of JNK1 with MKP5-CD and MKP5-KBD. (e) GST-mediated pull-down assays for interaction of JNK1 with MKP5-CD and MKP5-KBD.	FIG
47	51	JNK1	protein	(d) Gel filtration analysis for interaction of JNK1 with MKP5-CD and MKP5-KBD. (e) GST-mediated pull-down assays for interaction of JNK1 with MKP5-CD and MKP5-KBD.	FIG
57	61	MKP5	protein	(d) Gel filtration analysis for interaction of JNK1 with MKP5-CD and MKP5-KBD. (e) GST-mediated pull-down assays for interaction of JNK1 with MKP5-CD and MKP5-KBD.	FIG
62	64	CD	structure_element	(d) Gel filtration analysis for interaction of JNK1 with MKP5-CD and MKP5-KBD. (e) GST-mediated pull-down assays for interaction of JNK1 with MKP5-CD and MKP5-KBD.	FIG
69	73	MKP5	protein	(d) Gel filtration analysis for interaction of JNK1 with MKP5-CD and MKP5-KBD. (e) GST-mediated pull-down assays for interaction of JNK1 with MKP5-CD and MKP5-KBD.	FIG
74	77	KBD	structure_element	(d) Gel filtration analysis for interaction of JNK1 with MKP5-CD and MKP5-KBD. (e) GST-mediated pull-down assays for interaction of JNK1 with MKP5-CD and MKP5-KBD.	FIG
83	112	GST-mediated pull-down assays	experimental_method	(d) Gel filtration analysis for interaction of JNK1 with MKP5-CD and MKP5-KBD. (e) GST-mediated pull-down assays for interaction of JNK1 with MKP5-CD and MKP5-KBD.	FIG
132	136	JNK1	protein	(d) Gel filtration analysis for interaction of JNK1 with MKP5-CD and MKP5-KBD. (e) GST-mediated pull-down assays for interaction of JNK1 with MKP5-CD and MKP5-KBD.	FIG
142	146	MKP5	protein	(d) Gel filtration analysis for interaction of JNK1 with MKP5-CD and MKP5-KBD. (e) GST-mediated pull-down assays for interaction of JNK1 with MKP5-CD and MKP5-KBD.	FIG
147	149	CD	structure_element	(d) Gel filtration analysis for interaction of JNK1 with MKP5-CD and MKP5-KBD. (e) GST-mediated pull-down assays for interaction of JNK1 with MKP5-CD and MKP5-KBD.	FIG
154	158	MKP5	protein	(d) Gel filtration analysis for interaction of JNK1 with MKP5-CD and MKP5-KBD. (e) GST-mediated pull-down assays for interaction of JNK1 with MKP5-CD and MKP5-KBD.	FIG
159	162	KBD	structure_element	(d) Gel filtration analysis for interaction of JNK1 with MKP5-CD and MKP5-KBD. (e) GST-mediated pull-down assays for interaction of JNK1 with MKP5-CD and MKP5-KBD.	FIG
63	72	mutations	experimental_method	The panels are arranged the same as in Fig. 2d. (f) Effects of mutations in MKP5-CD on the JNK1 dephosphorylation (mean±s.e.m., n=3).	FIG
76	80	MKP5	protein	The panels are arranged the same as in Fig. 2d. (f) Effects of mutations in MKP5-CD on the JNK1 dephosphorylation (mean±s.e.m., n=3).	FIG
81	83	CD	structure_element	The panels are arranged the same as in Fig. 2d. (f) Effects of mutations in MKP5-CD on the JNK1 dephosphorylation (mean±s.e.m., n=3).	FIG
91	95	JNK1	protein	The panels are arranged the same as in Fig. 2d. (f) Effects of mutations in MKP5-CD on the JNK1 dephosphorylation (mean±s.e.m., n=3).	FIG
15	24	mutations	experimental_method	(g) Effects of mutations in MKP5-CD on the pNPP hydrolysis reaction (mean±s.e.m., n=3).	FIG
28	32	MKP5	protein	(g) Effects of mutations in MKP5-CD on the pNPP hydrolysis reaction (mean±s.e.m., n=3).	FIG
33	35	CD	structure_element	(g) Effects of mutations in MKP5-CD on the pNPP hydrolysis reaction (mean±s.e.m., n=3).	FIG
43	47	pNPP	chemical	(g) Effects of mutations in MKP5-CD on the pNPP hydrolysis reaction (mean±s.e.m., n=3).	FIG
4	20	Pull-down assays	experimental_method	(h) Pull-down assays of MKP5-CD by GST-tagged JNK1 mutants.	FIG
24	28	MKP5	protein	(h) Pull-down assays of MKP5-CD by GST-tagged JNK1 mutants.	FIG
29	31	CD	structure_element	(h) Pull-down assays of MKP5-CD by GST-tagged JNK1 mutants.	FIG
35	45	GST-tagged	protein_state	(h) Pull-down assays of MKP5-CD by GST-tagged JNK1 mutants.	FIG
46	50	JNK1	protein	(h) Pull-down assays of MKP5-CD by GST-tagged JNK1 mutants.	FIG
51	58	mutants	protein_state	(h) Pull-down assays of MKP5-CD by GST-tagged JNK1 mutants.	FIG