GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q92542	P49810	1	binding	up-regulates	0.941	Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2.	SIGNOR-81936
P62873	P59768	2	binding	up-regulates activity	0.94	GNB1 dissociates from the receptor, bound with GNG2 as stable dimer	SIGNOR-251105
P12956	P78527	2	relocalization	up-regulates	0.94	Ku and dna-pkcs only interact in the presence of dna and recruitment of dna-pkcs to sites of dna damage in vivo is ku-dependent. Inward translocation of ku allows dna-pkcs to interact with the extreme termini of the dna, allowing two dna-pkcs molecules to interact across the dsb in a so-called synaptic complex . This interaction stimulates the kinase activity of dna-pkcs, promoting phosphorylation in trans across the dsb (discussed in more detail below). Once assembled at the dna ends, the dna-pkcs-ku-dsb complex serves to tether the ends of the dsb together and protects the dna ends from nuclease attack.	SIGNOR-183276
P59768	P62873	2	binding	up-regulates activity	0.94	GNG2 dissociates from the activated receptor, bound with GNB1 as stable dimer.	SIGNOR-251106
P78527	P12956	2	phosphorylation	up-regulates activity	0.94	Ku70 phosphorylation occurs within minutes of genotoxic stress and involves DNA-PKcs and/or ATM kinase activities.By using specific vectors enabling the simultaneous shRNA-mediated inhibition of endogenous Ku70 and the expression of exogenous Ku70 resistant to shRNA (i.e. S27-S33-Ku70 and A27-A33-Ku70 expressing cells), we showed that phospho-Ku70 contributes to faster but error-prone DNA repair resulting in higher levels of chromosomal breaks.	SIGNOR-274023
Q14289	P49023	1	phosphorylation	down-regulates quantity by destabilization	0.94	P130Cas and paxillin can be phosphorylated by Fak or Pyk2, and bind directly to these kinases.	SIGNOR-279272
P34130	Q16620	1	binding	up-regulates	0.94	Its interactions with trkb can be distinguished from those of brain-derived neurotrophic factor (bdnf) with trkb.	SIGNOR-31644
Q15633	Q9UPY3	1	binding	up-regulates	0.94	Dicer and trbp interact in vivo and in vitro /our data indicate that trbp is primarily required for the assembly and/or functioning of si? Or mi?RISCs In mammalian cells, but it may also facilitate the cleavage of pre?miRNAs By dicer.	SIGNOR-140226
Q8WW43	Q92542	1	binding	up-regulates	0.94	By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain.These data indicate that maph-1 is probably a functional component of the gamma-secretase complex	SIGNOR-93307
P98170	P42574	1	ubiquitination	down-regulates quantity by destabilization	0.939	Xiap promotes the degradation of active-form caspase-3, but not procaspase-3, in living cells. Both the association of XIAP with caspase-3 and the RING finger domain of XIAP were essential for ubiquitination. XIAP promotes the degradation of caspase-3, which enhances its anti-apoptotic effect.	SIGNOR-109243
Q7RTN6	Q15831	2	phosphorylation	up-regulates quantity	0.939	Furthermore, interaction of STRAD with LKB1 promoted LKB1 phosphorylation at a PKA site S431 and elevated the LKB1 level, and overexpressing LKB1 with a serine-to-alanine mutation at S431 (LKB1 (S431A)) prevented axon differentiation.	SIGNOR-280149
Q15831	Q7RTN6	2	phosphorylation	up-regulates activity	0.939	Endogenous LKB1 and STRAD form a complex in which STRAD activates LKB1, resulting in phosphorylation of both partners.LKB1 phosphorylates STRAD at Thr329 and Thr419	SIGNOR-261950
Q13541	P06730	1	binding	down-regulates activity	0.939	The rate-limiting factor for translation is eukaryotic translation initiation factor 4E (eIF4E), which is negatively regulated by eIF4E-binding protein 1 (4E-BP1).	SIGNOR-167176
Q99570	Q8NEB9	1	binding	up-regulates	0.939	Recombinant p150 associated with ptdins 3-kinase in vitro in a stable manner, resulting in a 2-fold increase in lipid kinase activity.	SIGNOR-45664
P51532	Q8TAQ2	1	binding	up-regulates	0.939	The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added.	SIGNOR-65444
P09603	P07333	1	binding	up-regulates activity	0.938	The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34)	SIGNOR-255568
O00512	P35222	1	binding	up-regulates	0.938	The transcriptional activity of beta-catenin depends on bcl-9. Bcl-9 functions in targeting beta-catenin to the nucleus and thus increases the transcriptional activity of beta-catenin	SIGNOR-126059
O14965	Q9Y6A5	1	phosphorylation	up-regulates activity	0.937	We show that this conserved serine on human TACC3 (Ser(558)) is also phosphorylated by Aurora A. Moreover, phosphorylation of TACC3 by Aurora A in human cells is essential for its proper localization to centrosomes and proximal mitotic spindles. Inhibition of Aurora A with the selective small molecule inhibitor MLN8054 in cultured human tumor cells resulted in mislocalization of TACC3 away from mitotic spindles in a concentration-dependent manner.	SIGNOR-262655
P13501	P51681	1	binding	up-regulates activity	0.937	CCL5, also known RANTES (regulated on activation, normal T cell expressed and secreted), is a potent chemoattractant for a variety of leukocytes, including T cells, mono- cytes, NK cells, and basophils, signaling via the CCR1, CCR3, and CCR5 cell surface receptors [59]. Among these receptors, CCL5 has the highest affinity for CCR5.	SIGNOR-277726
P23443	P62753	1	phosphorylation	up-regulates activity	0.937	A knockin mouse carrying mutations at all phosphorylation sites in the primary s6k substrate, ribosomal protein s6 (rps6), has provided insight into the physiological role of this protein phosphorylation event. Of the many known substrates of s6k1, it is rps6 that has been shown to be directly involved, via its phosphorylation, in controlling cell size.	SIGNOR-135176
O95352	O94817	1	binding	up-regulates	0.937	Analogous to ubiquitination, atg12 is conjugated to atg5 by atg7--an e1-like protein--and atg10--an e2-like protein.	SIGNOR-180132
O95786	Q7Z434	1	binding	up-regulates activity	0.937	Initially, RIG-I and MDA5 sense dsRNA in the cytoplasm, produced as a by-product of RNA virus replication.Once one or both of these sensors are activated, they interact with a mitochondrial membrane protein called MAVS (mitochondrial antiviral) (also called IPS1, Cardif, and VISA). They signal to the mitochondrial membrane protein MAVS, which in turn activates the kinases TBK1 and IKKɛ.	SIGNOR-260139
P20827	P29317	1	binding	up-regulates	0.937	Ephrin-a1 binds and activates the tyrosine kinase activity of eph-a2, and has a dissociation constant of 20_30 nm	SIGNOR-56901
Q15628	Q13546	1	binding	up-regulates activity	0.937	We show that tradd interacts strongly with rip;rip is a serinethreonine kinase that is recruited by tradd to tnfr1 in a tnf-dependent process.	SIGNOR-40043
Q9NYJ8	O43318	1	binding	up-regulates activity	0.936	Our results indicate that two distinct TAK1 complexes are present in cells. One comprises TAK1 complexed with TAB1 and TAB2, and the other TAK1 complexed with TAB1 and TAB3. Both complexes are activated in response to tumour necrosis factor-alpha or interleukin-1 in human epithelial KB cells or bacterial lipopolysaccharide in RAW264.7 macrophages	SIGNOR-120268
P42336	P27986	2	phosphorylation	up-regulates activity	0.936	We find that p110 alpha phosphorylates p85 alpha Ser608 in vivo with significant stoichiometry. However, p110 beta is far less efficient at phosphorylating p85 alpha Ser608, identifying a potential difference in the mechanisms by which these two isoforms are regulated. The p85 alpha Ser608 phosphorylation was increased by treatment with insulin, platelet-derived growth factor, and the phosphatase inhibitor okadaic acid. The functional effects of this phosphorylation are highlighted by mutation of Ser608, which results in reduced lipid kinase activity and reduced association of the p110 alpha catalytic subunit with p85 alpha.	SIGNOR-276004
Q8NEB9	Q14457	1	binding	up-regulates activity	0.936	The beclin 1-vps34 interaction regulates autophagy.	SIGNOR-184521
P27986	P42336	2	binding	up-regulates activity	0.936	Signal transduction pathways triggered by Tie2 have been extensively examined. Tyr-1101of Tie2 directly associates in a phosphotyrosine (pTyr)-dependent manner with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, which in turn activate PI 3-kinase, leading to cell motility and survival	SIGNOR-242637
Q9NZQ7	Q15116	1	binding	up-regulates	0.936	Pd-l1, was found to bind pd-1 specifically. The functional significance of this interaction has been demonstrated in t cell assays, in which engagement of pd-1 by pd-l1 leads to the inhibition of tcr-mediated lymphocyte proliferation and cytokine secretion.	SIGNOR-82604
P51671	P51677	1	binding	up-regulates	0.936	Eotaxin (CCL11) is a specific ligand for CCR3 and serves as a potent chemoattractant for eosinophils	SIGNOR-254356
Q7LG56	P23921	1	binding	up-regulates activity	0.935	Taken together, we conclude that UV-induced activation of p53R2 transcription and binding of p53R2 to hRRM1 to form RR holoenzyme are impaired in the p53-mutant cell line PC3.	SIGNOR-259366
P01112	P04049	1	binding	up-regulates	0.935	We have examined whether the other two members of the Raf family, A-Raf and B-Raf, are regulated in a similar way to Raf-1. A-Raf behaves like Raf-1, being weakly activated by oncogenic Ras more strongly activated by oncogenic Src, and these signals synergize to give maximal activation. B-Raf by contrast is strongly activated by oncogenic Ras alone and is not activated by oncogenic Src.	SIGNOR-235786
P06493	Q12834	1	phosphorylation	down-regulates activity	0.935	Cdk1 phosphorylates Cdc20 to negatively regulate its ability to bind and activate the APC/C.	SIGNOR-279321
P49767	P35916	1	binding	up-regulates	0.935	Vegf-c, was isolated as a ligand for the tyrosine kinase vegfr-3 (flt4)	SIGNOR-55205
P21583	P10721	1	binding	up-regulates activity	0.934	The most relevant and still unique mast-cell growth factor is SCF, which is the ligand of KIT, a receptor with tyrosine-kinase activity that is expressed on the surface of all human and murine mast cells	SIGNOR-254946
P01308	P06213	1	binding	up-regulates activity	0.934	Our previous studies indicated that amino acid residues 240-250 in the cysteine-rich region of the human insulin receptor alpha-subunit constitute a site in which insulin binds.	SIGNOR-23001
P31948	P07900	1	binding	down-regulates activity	0.934	Hsp90 chaperone cycle is tightly regulated by another group of proteins referred to as ‘co-chaperones'. Their stability does not depend on Hsp90 function but they interact with distinct Hsp90 conformational states, providing directionality to the Hsp90 cycle. Furthermore, certain co-chaperones, such as HOP and Cdc37p50 inhibit the Hsp90 chaperone cycle, assisting in delivery of distinct sets of client proteins (steroid hormone receptors and kinases, respectively) to the Hsp90 chaperone machine.	SIGNOR-261411
P50591	O14763	1	binding	up-regulates	0.934	Tumour necrosis factor-related apoptosis inducing ligand (trail) receptor 2 (trail-r2) also known as tnfrsf10b (tumour necrosis factor receptor (tnfr) super family 10b) or killer/dr5, a member of the tnfr family, is a promising candidate tumour suppressor gene at 8p21-22.	SIGNOR-134524
P50591	O00220	1	binding	up-regulates	0.934	Trail interacts with tril-r1 and trail-r2 and activetes them	SIGNOR-101082
O00566	Q9NQZ2	1	binding	up-regulates activity	0.934	Mpp10 is able to bind the ribosome biogenesis factor Utp3/Sas10 through two conserved motifs in its N-terminal region. In addition, Mpp10 interacts with the ribosomal protein S5/uS7 using a short stretch within an acidic loop region. Thus, our findings reveal that Mpp10 provides a platform for the simultaneous interaction with multiple proteins in the 90S pre-ribosome.	SIGNOR-261176
P49815	Q92574	1	binding	up-regulates activity	0.934	Furthermore, tsc2 is directly phosphorylated by akt, which is involved in stimulating cell growth and is activated by growth stimulating signals, such as insulin. Tsc2 is inactivated by akt-dependent phosphorylation, which destabilizes tsc2 and disrupts its interaction with tsc1.	SIGNOR-77400
Q9Y4K3	Q9NYJ8	1	binding	up-regulates activity	0.933	The irak1/traf6 complex can also activate jnk and p38 signalling through assembly of a catalytically active tab2-tab3-tak1 complex.	SIGNOR-205458
P49366	P63241	1	post translational modification	up-regulates activity	0.933	Deoxyhypusine synthase (DHPS) utilizes spermidine and NAD as cofactors to incorporate a hypusine modification into the eukaryotic translation initiation factor 5A (eIF5A). Hypusine is essential for eIF5A activation, which, in turn, plays a key role in regulating protein translation of selected mRNA that are associated with the synthesis of oncoproteins, thereby enhancing tumor cell proliferation.	SIGNOR-266374
O43516	O00401	1	binding	up-regulates activity	0.933	Recruitment of N-WASP to vaccinia is mediated by WASP-interacting protein (WIP), whereas in Shigella WIP is recruited by N-WASP. Our observations show that vaccinia and Shigella activate the Arp2/3 complex to achieve actin-based motility, by mimicking either the SH2/SH3-containing adaptor or Cdc42 signalling pathways to recruit the N-WASP-WIP complex.	SIGNOR-261880
P78352	O14490	2	relocalization	up-regulates activity	0.932	Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b).	SIGNOR-264196
Q8IYD8	Q9NPI8	1	binding	up-regulates	0.932	Protein interaction motifs in fancm, designated mm1 and mm2, were identified. Mm1 interacts with the fa core complex by binding to fancf, whereas mm2 interacts with rm1 and topoisomerase iiialpha, components of the bs complex.	SIGNOR-163101
O14490	P78352	2	binding	up-regulates activity	0.932	SAPAPs are specifically expressed in neuronal cells and enriched in the PSD fraction. SAPAPs induce the enrichment of PSD-95/SAP90 to the plasma membrane in transfected cells. Thus, SAPAPs may have a potential activity to maintain the structure of PSD by concentrating its components to the membrane area.	SIGNOR-264209
Q13158	Q14790	1	binding	up-regulates activity	0.931	Fadd recruits caspase-8 through homotypic interactions of death-effector domains (deds), leading to caspase-8 activation and apoptosis. In turn, fadd recruits the zymogen form of the apoptosis-initiating protease caspase-8, through homophilic interaction of death effector domains.	SIGNOR-112061
P01375	P20333	1	binding	up-regulates activity	0.93	The binding of tnf to tnf-r1 triggers a series of intracellular events that ultimately result in the activation of two major transcription factors, nuclear factor kb (nf-kb) and c-jun.	SIGNOR-88216
P30990	P30989	1	binding	up-regulates	0.93	The rat neurotensin receptor cdna sequence was transfected in chinese hamster ovary cells and cellular clones which stably express the corresponding protein were isolated and characterized. The scatchard analysis of the specific binding of [3h]neurotensin indicated a kd value of 0.45 +/- 0.08 nm and a bmax value of 3.27 +/- 0.29 pmol/mg of protein. ...Neurotensin Stimulated the phosphoinositides hydrolysis	SIGNOR-17369
O43318	Q15750	2	phosphorylation	up-regulates activity	0.929	We identified amino acids (aa) 452/453 and 456/457 of TAB1 as novel sites phosphorylated by TAK1 as well as by p38 MAPK in intact cells as well as in vitro.	SIGNOR-276365
P29965	P25942	1	binding	up-regulates activity	0.929	Ramos cells were mixed with increasing numbers of transfected cells that expressed cd70 (cd27l) or cd154 (cd40l), both of which are expressed by activated T cells, in the presence of anti-igm ab. Cd27 ligation as well as cd40 ligation inhibited bcr-mediated apoptosis in a dose-dependent manner. cd40 binds its ligand cd40l.	SIGNOR-93432
P11802	P06400	1	phosphorylation	down-regulates	0.929	Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression.	SIGNOR-200487
O00273	O76075	1	binding	down-regulates	0.929	Dff is a heterodimer of 40 kda and 45 kda subunits.	SIGNOR-29729
P42345	P31749	2	phosphorylation	up-regulates activity	0.929	The rictor-mtor complex directly phosphorylated akt/pkb on ser473 in vitro and facilitated thr308 phosphorylation by pdk1	SIGNOR-252599
Q15750	O43318	2	binding	up-regulates activity	0.929	The yeast two-hybrid system has now revealed two human proteins, termed tab1 and tab2 (for tak1 binding protein), that interact with tak1. Overproduction of tab1 enhanced activity of the plasminogen activator inhibitor 1 gene promoter, which is regulated by tgf-beta, and increased the kinase activity of tak1. Tab1 activates the kinase activity of tak1 by directly binding to its catalytic domain. Tab1 overexpression increase the kinase activity of tak1 in mammalian cells.	SIGNOR-153031
P12643	P36894	1	binding	up-regulates	0.929	BMP interacts with specific receptors on the cell surface, BMP receptor types 1 and 2 (BMPr1 and BMPr2).	SIGNOR-253547
O75381	P50542	1	binding	up-regulates activity	0.929	The peroxisomal docking complex is a key component of the import machinery for matrix proteins. The core protein of this complex, Pex14, is thought to represent the initial docking site for the import receptors Pex5 and Pex7.	SIGNOR-253027
P31749	P42345	2	phosphorylation	up-regulates	0.929	Once phosphorylated, Akt can act on a broad spectrum of substrates that can influence cell survival and proliferation and protein synthesis (65). Phosphorylation of mTOR by Akt leads to mTOR activation (40, 52) and the subsequent activation of p70S6K	SIGNOR-255107
P00797	P01019	2	cleavage	up-regulates activity	0.928	Angiotensinogen, an _-glycoprotein, is released from the liver (152, 250, 444) and is cleaved in the circulation by the enzyme renin that is secreted from the juxtaglomerular apparatus of the kidney (245, 250, 540, 631) to form the decapeptide angiotensin (ANG) I	SIGNOR-252297
P01019	P00797	2	binding	up-regulates activity	0.928	Renin is an aspartic protease that enzymatically cleaves its substrate angiotensinogen, which is produced by the liver, to form an inactive peptide: angiotensin (Ang)I or Ang (1–10).	SIGNOR-260224
P14210	P08581	1	binding	up-regulates	0.928	Hgf is the ligand for p190met, the receptor tyrosine kinase encoded by the met proto-oncogene.	SIGNOR-38429
Q15276	P20339	1	binding	up-regulates	0.928	We have previously shown that rab5, which regulates various steps of transport along the early endocytic pathway, is activated by a complex consisting of rabex-5, a rab5 nucleotide exchange factor, and the effector rabaptin-5.	SIGNOR-109352
P62826	O14980	1	binding	up-regulates activity	0.928	The nuclear export by CRM1 requires an interaction with the small GTPase Ras-related nuclear antigen (Ran), which cycles between GTP- and GDP-bound states. The binding of Ran GTP to CRM1 in the nucleus increases the affinity of CRM1 for cargo proteins	SIGNOR-275848
P46937	Q15561	1	binding	up-regulates activity	0.927	The multifunctional cytokine TGF-β has been identified as a potent inducer of CTGF expression, activating CTGF transcription through the canonical Smad signaling pathway. It is worth noting that TGF-β synergizes with Hippo–Yes-associated protein (YAP) signaling, a key regulator of tumorigenesis, to induce the expression of CTGF by the formation of a YAP-TEAD4-Smad3-p300 complex on the CTGF promoter	SIGNOR-277685
P60568	P01589	1	binding	up-regulates	0.927	Il-2 is a cytokine that functions as a growth factor and central regulator in the immune system and mediates its effects through ligand-induced hetero-trimerization of the receptor subunits il-2r alpha, il-2r beta, and gamma(c).	SIGNOR-144537
Q14242	P16109	1	binding	up-regulates	0.927	The major ligand for p-selectin on leukocytes is p-selectin glycoprotein ligand-1 (PSGL-1)	SIGNOR-47625
P42345	Q13541	1	phosphorylation	down-regulates activity	0.926	Specifically as part of mTORC1, mTOR directly phosphorylates the ribo- somal protein S6 kinases (S6K1 and S6K2) and the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BP1 and 4E-BP2), both of which control specific steps in the initiation of cap-dependent translation	SIGNOR-167184
P25791	P17542	1	binding	up-regulates	0.926	Transcriptional activity of tal1 in t cell acute lymphoblastic leukemia (t-all) requires rbtn1 or -2	SIGNOR-46161
P01375	P19438	1	binding	up-regulates activity	0.925	For TNFR1, the cytokine TNFα binds to the receptor and triggers its trimerization, which leads to the assembly of the receptor complex and initiation of signaling.	SIGNOR-199091
Q13535	O14757	1	phosphorylation	up-regulates	0.925	Atr activation typically leads to chk1 phosphorylation and activation. In response to genotoxic stress, chk1 is phosphorylated on serines 317 (s317) and 345 (s345) by the ataxia-telangiectasia-related (atr) protein kinase.	SIGNOR-134716
Q13131	Q9Y478	1	phosphorylation	up-regulates	0.925	Mutation of serine 108 to alanine, an autophosphorylation site within the glycogen binding domain of the beta1 subunit, almost completely abolishes activation of ampk by a-769662 in cells and in vitro, while only partially reducing activation by amp	SIGNOR-157553
O95760	Q01638	1	binding	up-regulates activity	0.925	We report a member of the IL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T(H)2 cells. In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs.The binding of IL-33 to cells that express ST2 results in the activation of NF-κB and MAP kinases. Administration of purified IL-33 either in vitro or in vivo leads to the production of TH2-associated cytokines.	SIGNOR-277711
Q969D9	Q9HC73	1	binding	up-regulates	0.924	Human tslp is proposed to signal through a heterodimeric receptor complex that consists of a new member of the hemopoietin family termed human tslp receptor and the il-7r alpha-chain.	SIGNOR-108920
Q16552	Q96F46	1	binding	up-regulates	0.924	Binding studies suggest that recombinant hil-17 binds to the hil-17r with low affinity. Monoclonal antibodies (mabs) generated against the hil-17r were able to block the il-17-induced production of cytokine from human foreskin fibroblast (hff) cells.	SIGNOR-53249
O15123	Q02763	1	binding	up-regulates	0.924	Angiopoietin-1 and -2, bound to tek with similar affinities, and angiopoietin-1 effectively induced tek phosphorylation in hematopoietic cells. Angiopoietin-2 also induced a low level of tek phosphorylation and weakened the phosphorylation induced by angiopoietin-1	SIGNOR-59808
O43921	P54764	1	binding	up-regulates	0.924	Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor	SIGNOR-52203
Q12824	P51531	1	binding	up-regulates activity	0.924	The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added.	SIGNOR-65181
P01112	P42336	1	binding	up-regulates	0.924	In vivo, dominant negative ras mutant n17 inhibits growth factor induced production of 3' phosphorylated phosphoinositides in pc12 cells, and transfection of ras, but not raf, into cos cells results in a large elevation in the level of these lipids. Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. it was also described that ras interacts with pi3k in a direct manner. lysine residue 227 is essential for the interaction of ras with pi3k	SIGNOR-35878
P01236	P16471	1	binding	up-regulates	0.924	Prolactin-dependent signaling occurs as the result of ligand-induced dimerization of the prolactin receptor (prlr).	SIGNOR-72810
Q15835	P08100	1	phosphorylation	up-regulates activity	0.923	That light-dependent phosphorylation of Rho is mediated primarily by RK. Addition of an inhibitory antibody against rhodopsin kinase (RK) lowered phosphorylation at Ser334, Ser338, and Ser343, without changing the ratio between phosphorylation sites. upon illumination, Ser334c, Ser338, and Ser343 are phosphorylated.	SIGNOR-251190
P00533	P62993	1	binding	up-regulates activity	0.923	Adaptor protein Grb2 binds phosphotyrosines in the epidermal growth factor (EGF) receptor (EGFR) and thereby links receptor activation to intracellular signaling cascades.	SIGNOR-267725
Q92585	P46531	1	binding	up-regulates	0.923	Maml1 binds to the ankyrin repeat domain of all four mammalian notch receptors, forms a dna-binding complex with icn and rbp-jkappa, and amplifies notch-induced transcription of hes1.Maml1 functions as a transcriptional co-activator for notch signalling.	SIGNOR-86117
Q96BI3	P49810	1	binding	up-regulates	0.923	Gamma secretase subunit. Leads to ps1/ps2 eterodimer complex stabilisation. By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain.	SIGNOR-93265
Q9UJ41	P20339	1	binding	up-regulates	0.923	We have previously shown that rab5, which regulates various steps of transport along the early endocytic pathway, is activated by a complex consisting of rabex-5, a rab5 nucleotide exchange factor, and the effector rabaptin-5.	SIGNOR-109398
P12931	O60716	1	phosphorylation	up-regulates activity	0.922	Identification of Src phosphorylation sites in the catenin p120ctn.Using selected tyrosine to phenylalanine p120 mutants as dominant negative reagents, it may now be possible to selectively block events postulated to be dependent on p120 tyrosine phosphorylation.combinations of Tyr _ Phe mutations at residues 96, 112, 228, 257, 280, 291, 296, and 302	SIGNOR-246484
P98170	P55211	1	binding	down-regulates quantity by destabilization	0.922	A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis	SIGNOR-105702
P53350	P14635	1	phosphorylation	up-regulates activity	0.922	Phosphorylation of cyclin b1 is central to its nuclear translocationduring cell-cycle progression in hela cells, a change in the kinase activity of endogenous plk1 toward s147 and/or s133 correlates with a kinase activity in the cell extractsa mutant cyclin b1 in which s133 and s147 are replaced by alanines remains in the cytoplasm, whereas wild-type cyclin b1 accumulates in the nucleus during prophase.Together, these results suggest that phosphorylation of s133 and s147 is necessary for the nuclear translocation of cyclin b1 during prophase, and that phosphorylation of s126 and s128 may stimulate the nuclear translocation.	SIGNOR-105719
P52803	P29317	1	binding	up-regulates	0.922	Members of the epha subfamily of receptor tyrosine kinases and their ephrin-a ligands have been implicated in the guidance of retinal axons along the anterior-posterior axis of the chick optic tectum.	SIGNOR-52467
O14920	P25963	1	phosphorylation	down-regulates activity	0.922	Tak1 become activated and then phosphorilates and activates ikk2 which in turn now phosphorylates ikba, marking it for k48-ubiquitination and proteasomal degradation	SIGNOR-235400
P61764	Q16623	1	binding	up-regulates activity	0.922	Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis. We have now identified two Munc18-1-interacting proteins called Mint1 and Mint2 that may mediate the function of Munc18-1.	SIGNOR-264042
P49815	Q15382	1	gtpase-activating protein	down-regulates activity	0.922	Tsc2 functions as a gap to inhibit rheb activity. Tsc2 displays gap (gtpase-activating protein) activity specifically towards the small g protein rheb and inhibits its ability to stimulate the mtor signaling pathway. It has recently been shown that tsc2 has gtpase-activating protein (gap) activity towards the ras family small gtpase rheb (ras homolog enriched in brain), and tsc1/2 antagonizes the mtor signaling pathway via stimulation of gtp hydrolysis of rheb.	SIGNOR-128432
Q99836	Q9Y4K3	1	binding	up-regulates activity	0.922	In innate immunity, nearly all Toll-like receptors (TLRs), as well as the receptors of the interleukin 1 (IL-1) family of cytokines, initiate signaling by recruiting the adaptor protein MyD88. This is followed by the interaction of IL-1-receptor (IL-R)-associated kinase 4 (IRAK4) with MyD88 and then the interaction of other IRAK family members with IRAK4, to form an oligomeric complex, termed the Myddosome (8, 9). IRAK1 and IRAK2 can then interact with TRAF6 (10, 11) and induce TRAF6 dimerization (12), which triggers the activation of its E3 ligase activity	SIGNOR-260160
P20701	P05362	1	binding	up-regulates	0.922	This leads to further neutrophil-endothelial cell interactions through the binding of LFA-1 to its endothelial counterreceptor ICAM-1 during the slow rolling phase	SIGNOR-255040
P06400	Q01094	1	binding	down-regulates activity	0.921	E2f binds rb. E2f activation domain is the target for rb-induced repression. Rb can silence the 57 residue e2f activation domain. Rb can mask e2f residues involved in the activation process, possibly by mimicking a component of the transcriptional machinery	SIGNOR-37305
P23510	P43489	1	binding	up-regulates	0.921	Activation of nf-kappab in ox40-transfected hsb-2 cells was detected by electrophoretic mobility shift assay within 30 min after the binding of the ligand gp34.	SIGNOR-54927
P13984	P19388	1	binding	up-regulates activity	0.921	Direct Interaction Between the Subunit RAP30 of Transcription Factor IIF (TFIIF) and RNA Polymerase Subunit 5, Which Contributes to the Association Between TFIIF and RNA Polymerase II. we showed that RPB5 binds RAP30 but not RAP74 and associates to TFIIF through the binding to RAP30.	SIGNOR-261179
Q00978	P52630	1	binding	up-regulates activity	0.921	Coimmunoprecipitation assays demonstrate p48 association with STAT2 but not STAT1.The studies demonstrate the in vivo existence of a STAT2.p48 complex and a distinct STAT2.STAT1 complex after IFN-alpha stimulation. Data suggest that distinct bipartite complexes STAT2.p48 and STAT2.STAT1 translocate to the nucleus and associate on the DNA target site as ISGF3.	SIGNOR-217806
Q7L9L4	O95835	1	binding	up-regulates	0.921	Lats1/2 are activated by association with the highly homologous scaffold proteins mps one binder kinase activator-like 1a (mobkl1a) and 1b (mobkl1b), which are collectively referred to as mob1.	SIGNOR-169795
O43791	Q13618	1	binding	up-regulates activity	0.921	Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127.	SIGNOR-268927

Q92542

P49810

1

binding

up-regulates

0.941

Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2.

SIGNOR-81936

P62873

P59768

2

binding

up-regulates activity

0.94

GNB1 dissociates from the receptor, bound with GNG2 as stable dimer

SIGNOR-251105

P12956

P78527

2

relocalization

up-regulates

0.94

Ku and dna-pkcs only interact in the presence of dna and recruitment of dna-pkcs to sites of dna damage in vivo is ku-dependent. Inward translocation of ku allows dna-pkcs to interact with the extreme termini of the dna, allowing two dna-pkcs molecules to interact across the dsb in a so-called synaptic complex . This interaction stimulates the kinase activity of dna-pkcs, promoting phosphorylation in trans across the dsb (discussed in more detail below). Once assembled at the dna ends, the dna-pkcs-ku-dsb complex serves to tether the ends of the dsb together and protects the dna ends from nuclease attack.

SIGNOR-183276

P59768

P62873

2

binding

up-regulates activity

0.94

GNG2 dissociates from the activated receptor, bound with GNB1 as stable dimer.

SIGNOR-251106

P78527

P12956

2

phosphorylation

up-regulates activity

0.94

Ku70 phosphorylation occurs within minutes of genotoxic stress and involves DNA-PKcs and/or ATM kinase activities.By using specific vectors enabling the simultaneous shRNA-mediated inhibition of endogenous Ku70 and the expression of exogenous Ku70 resistant to shRNA (i.e. S27-S33-Ku70 and A27-A33-Ku70 expressing cells), we showed that phospho-Ku70 contributes to faster but error-prone DNA repair resulting in higher levels of chromosomal breaks.

SIGNOR-274023

Q14289

P49023

1

phosphorylation

down-regulates quantity by destabilization

0.94

P130Cas and paxillin can be phosphorylated by Fak or Pyk2, and bind directly to these kinases.

SIGNOR-279272

P34130

Q16620

1

binding

up-regulates

0.94

Its interactions with trkb can be distinguished from those of brain-derived neurotrophic factor (bdnf) with trkb.

SIGNOR-31644

Q15633

Q9UPY3

1

binding

up-regulates

0.94

Dicer and trbp interact in vivo and in vitro /our data indicate that trbp is primarily required for the assembly and/or functioning of si? Or mi?RISCs In mammalian cells, but it may also facilitate the cleavage of pre?miRNAs By dicer.

SIGNOR-140226

Q8WW43

Q92542

1

binding

up-regulates

0.94

By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain.These data indicate that maph-1 is probably a functional component of the gamma-secretase complex

SIGNOR-93307

P98170

P42574

1

ubiquitination

down-regulates quantity by destabilization

0.939

Xiap promotes the degradation of active-form caspase-3, but not procaspase-3, in living cells. Both the association of XIAP with caspase-3 and the RING finger domain of XIAP were essential for ubiquitination. XIAP promotes the degradation of caspase-3, which enhances its anti-apoptotic effect.

SIGNOR-109243

Q7RTN6

Q15831

2

phosphorylation

up-regulates quantity

0.939

Furthermore, interaction of STRAD with LKB1 promoted LKB1 phosphorylation at a PKA site S431 and elevated the LKB1 level, and overexpressing LKB1 with a serine-to-alanine mutation at S431 (LKB1 (S431A)) prevented axon differentiation.

SIGNOR-280149

Q15831

Q7RTN6

2

phosphorylation

up-regulates activity

0.939

Endogenous LKB1 and STRAD form a complex in which STRAD activates LKB1, resulting in phosphorylation of both partners.LKB1 phosphorylates STRAD at Thr329 and Thr419

SIGNOR-261950

Q13541

P06730

1

binding

down-regulates activity

0.939

The rate-limiting factor for translation is eukaryotic translation initiation factor 4E (eIF4E), which is negatively regulated by eIF4E-binding protein 1 (4E-BP1).

SIGNOR-167176

Q99570

Q8NEB9

1

binding

up-regulates

0.939

Recombinant p150 associated with ptdins 3-kinase in vitro in a stable manner, resulting in a 2-fold increase in lipid kinase activity.

SIGNOR-45664

P51532

Q8TAQ2

1

binding

up-regulates

0.939

The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added.

SIGNOR-65444

P09603

P07333

1

binding

up-regulates activity

0.938

The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34)

SIGNOR-255568

O00512

P35222

1

binding

up-regulates

0.938

The transcriptional activity of beta-catenin depends on bcl-9. Bcl-9 functions in targeting beta-catenin to the nucleus and thus increases the transcriptional activity of beta-catenin

SIGNOR-126059

O14965

Q9Y6A5

1

phosphorylation

up-regulates activity

0.937

We show that this conserved serine on human TACC3 (Ser(558)) is also phosphorylated by Aurora A. Moreover, phosphorylation of TACC3 by Aurora A in human cells is essential for its proper localization to centrosomes and proximal mitotic spindles. Inhibition of Aurora A with the selective small molecule inhibitor MLN8054 in cultured human tumor cells resulted in mislocalization of TACC3 away from mitotic spindles in a concentration-dependent manner.

SIGNOR-262655

P13501

P51681

1

binding

up-regulates activity

0.937

CCL5, also known RANTES (regulated on activation, normal T cell expressed and secreted), is a potent chemoattractant for a variety of leukocytes, including T cells, mono- cytes, NK cells, and basophils, signaling via the CCR1, CCR3, and CCR5 cell surface receptors [59]. Among these receptors, CCL5 has the highest affinity for CCR5.

SIGNOR-277726

P23443

P62753

1

phosphorylation

up-regulates activity

0.937

A knockin mouse carrying mutations at all phosphorylation sites in the primary s6k substrate, ribosomal protein s6 (rps6), has provided insight into the physiological role of this protein phosphorylation event. Of the many known substrates of s6k1, it is rps6 that has been shown to be directly involved, via its phosphorylation, in controlling cell size.

SIGNOR-135176

O95352

O94817

1

binding

up-regulates

0.937

Analogous to ubiquitination, atg12 is conjugated to atg5 by atg7--an e1-like protein--and atg10--an e2-like protein.

SIGNOR-180132

O95786

Q7Z434

1

binding

up-regulates activity

0.937

Initially, RIG-I and MDA5 sense dsRNA in the cytoplasm, produced as a by-product of RNA virus replication.Once one or both of these sensors are activated, they interact with a mitochondrial membrane protein called MAVS (mitochondrial antiviral) (also called IPS1, Cardif, and VISA). They signal to the mitochondrial membrane protein MAVS, which in turn activates the kinases TBK1 and IKKɛ.

SIGNOR-260139

P20827

P29317

1

binding

up-regulates

0.937

Ephrin-a1 binds and activates the tyrosine kinase activity of eph-a2, and has a dissociation constant of 20_30 nm

SIGNOR-56901

Q15628

Q13546

1

binding

up-regulates activity

0.937

We show that tradd interacts strongly with rip;rip is a serinethreonine kinase that is recruited by tradd to tnfr1 in a tnf-dependent process.

SIGNOR-40043

Q9NYJ8

O43318

1

binding

up-regulates activity

0.936

Our results indicate that two distinct TAK1 complexes are present in cells. One comprises TAK1 complexed with TAB1 and TAB2, and the other TAK1 complexed with TAB1 and TAB3. Both complexes are activated in response to tumour necrosis factor-alpha or interleukin-1 in human epithelial KB cells or bacterial lipopolysaccharide in RAW264.7 macrophages

SIGNOR-120268

P42336

P27986

2

phosphorylation

up-regulates activity

0.936

We find that p110 alpha phosphorylates p85 alpha Ser608 in vivo with significant stoichiometry. However, p110 beta is far less efficient at phosphorylating p85 alpha Ser608, identifying a potential difference in the mechanisms by which these two isoforms are regulated. The p85 alpha Ser608 phosphorylation was increased by treatment with insulin, platelet-derived growth factor, and the phosphatase inhibitor okadaic acid. The functional effects of this phosphorylation are highlighted by mutation of Ser608, which results in reduced lipid kinase activity and reduced association of the p110 alpha catalytic subunit with p85 alpha.

SIGNOR-276004

Q8NEB9

Q14457

1

binding

up-regulates activity

0.936

The beclin 1-vps34 interaction regulates autophagy.

SIGNOR-184521

P27986

P42336

2

binding

up-regulates activity

0.936

Signal transduction pathways triggered by Tie2 have been extensively examined. Tyr-1101of Tie2 directly associates in a phosphotyrosine (pTyr)-dependent manner with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, which in turn activate PI 3-kinase, leading to cell motility and survival

SIGNOR-242637

Q9NZQ7

Q15116

1

binding

up-regulates

0.936

Pd-l1, was found to bind pd-1 specifically. The functional significance of this interaction has been demonstrated in t cell assays, in which engagement of pd-1 by pd-l1 leads to the inhibition of tcr-mediated lymphocyte proliferation and cytokine secretion.

SIGNOR-82604

P51671

P51677

1

binding

up-regulates

0.936

Eotaxin (CCL11) is a specific ligand for CCR3 and serves as a potent chemoattractant for eosinophils

SIGNOR-254356

Q7LG56

P23921

1

binding

up-regulates activity

0.935

Taken together, we conclude that UV-induced activation of p53R2 transcription and binding of p53R2 to hRRM1 to form RR holoenzyme are impaired in the p53-mutant cell line PC3.

SIGNOR-259366

P01112

P04049

1

binding

up-regulates

0.935

We have examined whether the other two members of the Raf family, A-Raf and B-Raf, are regulated in a similar way to Raf-1. A-Raf behaves like Raf-1, being weakly activated by oncogenic Ras more strongly activated by oncogenic Src, and these signals synergize to give maximal activation. B-Raf by contrast is strongly activated by oncogenic Ras alone and is not activated by oncogenic Src.

SIGNOR-235786

P06493

Q12834

1

phosphorylation

down-regulates activity

0.935

Cdk1 phosphorylates Cdc20 to negatively regulate its ability to bind and activate the APC/C.

SIGNOR-279321

P49767

P35916

1

binding

up-regulates

0.935

Vegf-c, was isolated as a ligand for the tyrosine kinase vegfr-3 (flt4)

SIGNOR-55205

P21583

P10721

1

binding

up-regulates activity

0.934

The most relevant and still unique mast-cell growth factor is SCF, which is the ligand of KIT, a receptor with tyrosine-kinase activity that is expressed on the surface of all human and murine mast cells

SIGNOR-254946

P01308

P06213

1

binding

up-regulates activity

0.934

Our previous studies indicated that amino acid residues 240-250 in the cysteine-rich region of the human insulin receptor alpha-subunit constitute a site in which insulin binds.

SIGNOR-23001

P31948

P07900

1

binding

down-regulates activity

0.934

Hsp90 chaperone cycle is tightly regulated by another group of proteins referred to as ‘co-chaperones'. Their stability does not depend on Hsp90 function but they interact with distinct Hsp90 conformational states, providing directionality to the Hsp90 cycle. Furthermore, certain co-chaperones, such as HOP and Cdc37p50 inhibit the Hsp90 chaperone cycle, assisting in delivery of distinct sets of client proteins (steroid hormone receptors and kinases, respectively) to the Hsp90 chaperone machine.

SIGNOR-261411

P50591

O14763

1

binding

up-regulates

0.934

Tumour necrosis factor-related apoptosis inducing ligand (trail) receptor 2 (trail-r2) also known as tnfrsf10b (tumour necrosis factor receptor (tnfr) super family 10b) or killer/dr5, a member of the tnfr family, is a promising candidate tumour suppressor gene at 8p21-22.

SIGNOR-134524

P50591

O00220

1

binding

up-regulates

0.934

Trail interacts with tril-r1 and trail-r2 and activetes them

SIGNOR-101082

O00566

Q9NQZ2

1

binding

up-regulates activity

0.934

Mpp10 is able to bind the ribosome biogenesis factor Utp3/Sas10 through two conserved motifs in its N-terminal region. In addition, Mpp10 interacts with the ribosomal protein S5/uS7 using a short stretch within an acidic loop region. Thus, our findings reveal that Mpp10 provides a platform for the simultaneous interaction with multiple proteins in the 90S pre-ribosome.

SIGNOR-261176

P49815

Q92574

1

binding

up-regulates activity

0.934

Furthermore, tsc2 is directly phosphorylated by akt, which is involved in stimulating cell growth and is activated by growth stimulating signals, such as insulin. Tsc2 is inactivated by akt-dependent phosphorylation, which destabilizes tsc2 and disrupts its interaction with tsc1.

SIGNOR-77400

Q9Y4K3

Q9NYJ8

1

binding

up-regulates activity

0.933

The irak1/traf6 complex can also activate jnk and p38 signalling through assembly of a catalytically active tab2-tab3-tak1 complex.

SIGNOR-205458

P49366

P63241

1

post translational modification

up-regulates activity

0.933

Deoxyhypusine synthase (DHPS) utilizes spermidine and NAD as cofactors to incorporate a hypusine modification into the eukaryotic translation initiation factor 5A (eIF5A). Hypusine is essential for eIF5A activation, which, in turn, plays a key role in regulating protein translation of selected mRNA that are associated with the synthesis of oncoproteins, thereby enhancing tumor cell proliferation.

SIGNOR-266374

O43516

O00401

1

binding

up-regulates activity

0.933

Recruitment of N-WASP to vaccinia is mediated by WASP-interacting protein (WIP), whereas in Shigella WIP is recruited by N-WASP. Our observations show that vaccinia and Shigella activate the Arp2/3 complex to achieve actin-based motility, by mimicking either the SH2/SH3-containing adaptor or Cdc42 signalling pathways to recruit the N-WASP-WIP complex.

SIGNOR-261880

P78352

O14490

2

relocalization

up-regulates activity

0.932

Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b).

SIGNOR-264196

Q8IYD8

Q9NPI8

1

binding

up-regulates

0.932

Protein interaction motifs in fancm, designated mm1 and mm2, were identified. Mm1 interacts with the fa core complex by binding to fancf, whereas mm2 interacts with rm1 and topoisomerase iiialpha, components of the bs complex.

SIGNOR-163101

O14490

P78352

2

binding

up-regulates activity

0.932

SAPAPs are specifically expressed in neuronal cells and enriched in the PSD fraction. SAPAPs induce the enrichment of PSD-95/SAP90 to the plasma membrane in transfected cells. Thus, SAPAPs may have a potential activity to maintain the structure of PSD by concentrating its components to the membrane area.

SIGNOR-264209

Q13158

Q14790

1

binding

up-regulates activity

0.931

Fadd recruits caspase-8 through homotypic interactions of death-effector domains (deds), leading to caspase-8 activation and apoptosis. In turn, fadd recruits the zymogen form of the apoptosis-initiating protease caspase-8, through homophilic interaction of death effector domains.

SIGNOR-112061

P01375

P20333

1

binding

up-regulates activity

0.93

The binding of tnf to tnf-r1 triggers a series of intracellular events that ultimately result in the activation of two major transcription factors, nuclear factor kb (nf-kb) and c-jun.

SIGNOR-88216

P30990

P30989

1

binding

up-regulates

0.93

The rat neurotensin receptor cdna sequence was transfected in chinese hamster ovary cells and cellular clones which stably express the corresponding protein were isolated and characterized. The scatchard analysis of the specific binding of [3h]neurotensin indicated a kd value of 0.45 +/- 0.08 nm and a bmax value of 3.27 +/- 0.29 pmol/mg of protein. ...Neurotensin Stimulated the phosphoinositides hydrolysis

SIGNOR-17369

O43318

Q15750

2

phosphorylation

up-regulates activity

0.929

We identified amino acids (aa) 452/453 and 456/457 of TAB1 as novel sites phosphorylated by TAK1 as well as by p38 MAPK in intact cells as well as in vitro.

SIGNOR-276365

P29965

P25942

1

binding

up-regulates activity

0.929

Ramos cells were mixed with increasing numbers of transfected cells that expressed cd70 (cd27l) or cd154 (cd40l), both of which are expressed by activated T cells, in the presence of anti-igm ab. Cd27 ligation as well as cd40 ligation inhibited bcr-mediated apoptosis in a dose-dependent manner. cd40 binds its ligand cd40l.

SIGNOR-93432

P11802

P06400

1

phosphorylation

down-regulates

0.929

Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression.

SIGNOR-200487

O00273

O76075

1

binding

down-regulates

0.929

Dff is a heterodimer of 40 kda and 45 kda subunits.

SIGNOR-29729

P42345

P31749

2

phosphorylation

up-regulates activity

0.929

The rictor-mtor complex directly phosphorylated akt/pkb on ser473 in vitro and facilitated thr308 phosphorylation by pdk1

SIGNOR-252599

Q15750

O43318

2

binding

up-regulates activity

0.929

The yeast two-hybrid system has now revealed two human proteins, termed tab1 and tab2 (for tak1 binding protein), that interact with tak1. Overproduction of tab1 enhanced activity of the plasminogen activator inhibitor 1 gene promoter, which is regulated by tgf-beta, and increased the kinase activity of tak1. Tab1 activates the kinase activity of tak1 by directly binding to its catalytic domain. Tab1 overexpression increase the kinase activity of tak1 in mammalian cells.

SIGNOR-153031

P12643

P36894

1

binding

up-regulates

0.929

BMP interacts with specific receptors on the cell surface, BMP receptor types 1 and 2 (BMPr1 and BMPr2).

SIGNOR-253547

O75381

P50542

1

binding

up-regulates activity

0.929

The peroxisomal docking complex is a key component of the import machinery for matrix proteins. The core protein of this complex, Pex14, is thought to represent the initial docking site for the import receptors Pex5 and Pex7.

SIGNOR-253027

P31749

P42345

2

phosphorylation

up-regulates

0.929

Once phosphorylated, Akt can act on a broad spectrum of substrates that can influence cell survival and proliferation and protein synthesis (65). Phosphorylation of mTOR by Akt leads to mTOR activation (40, 52) and the subsequent activation of p70S6K

SIGNOR-255107

P00797

P01019

2

cleavage

up-regulates activity

0.928

Angiotensinogen, an _-glycoprotein, is released from the liver (152, 250, 444) and is cleaved in the circulation by the enzyme renin that is secreted from the juxtaglomerular apparatus of the kidney (245, 250, 540, 631) to form the decapeptide angiotensin (ANG) I

SIGNOR-252297

P01019

P00797

2

binding

up-regulates activity

0.928

Renin is an aspartic protease that enzymatically cleaves its substrate angiotensinogen, which is produced by the liver, to form an inactive peptide: angiotensin (Ang)I or Ang (1–10).

SIGNOR-260224

P14210

P08581

1

binding

up-regulates

0.928

Hgf is the ligand for p190met, the receptor tyrosine kinase encoded by the met proto-oncogene.

SIGNOR-38429

Q15276

P20339

1

binding

up-regulates

0.928

We have previously shown that rab5, which regulates various steps of transport along the early endocytic pathway, is activated by a complex consisting of rabex-5, a rab5 nucleotide exchange factor, and the effector rabaptin-5.

SIGNOR-109352

P62826

O14980

1

binding

up-regulates activity

0.928

The nuclear export by CRM1 requires an interaction with the small GTPase Ras-related nuclear antigen (Ran), which cycles between GTP- and GDP-bound states. The binding of Ran GTP to CRM1 in the nucleus increases the affinity of CRM1 for cargo proteins

SIGNOR-275848

P46937

Q15561

1

binding

up-regulates activity

0.927

The multifunctional cytokine TGF-β has been identified as a potent inducer of CTGF expression, activating CTGF transcription through the canonical Smad signaling pathway. It is worth noting that TGF-β synergizes with Hippo–Yes-associated protein (YAP) signaling, a key regulator of tumorigenesis, to induce the expression of CTGF by the formation of a YAP-TEAD4-Smad3-p300 complex on the CTGF promoter

SIGNOR-277685

P60568

P01589

1

binding

up-regulates

0.927

Il-2 is a cytokine that functions as a growth factor and central regulator in the immune system and mediates its effects through ligand-induced hetero-trimerization of the receptor subunits il-2r alpha, il-2r beta, and gamma(c).

SIGNOR-144537

Q14242

P16109

1

binding

up-regulates

0.927

The major ligand for p-selectin on leukocytes is p-selectin glycoprotein ligand-1 (PSGL-1)

SIGNOR-47625

P42345

Q13541

1

phosphorylation

down-regulates activity

0.926

Specifically as part of mTORC1, mTOR directly phosphorylates the ribo- somal protein S6 kinases (S6K1 and S6K2) and the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BP1 and 4E-BP2), both of which control specific steps in the initiation of cap-dependent translation

SIGNOR-167184

P25791

P17542

1

binding

up-regulates

0.926

Transcriptional activity of tal1 in t cell acute lymphoblastic leukemia (t-all) requires rbtn1 or -2

SIGNOR-46161

P01375

P19438

1

binding

up-regulates activity

0.925

For TNFR1, the cytokine TNFα binds to the receptor and triggers its trimerization, which leads to the assembly of the receptor complex and initiation of signaling.

SIGNOR-199091

Q13535

O14757

1

phosphorylation

up-regulates

0.925

Atr activation typically leads to chk1 phosphorylation and activation. In response to genotoxic stress, chk1 is phosphorylated on serines 317 (s317) and 345 (s345) by the ataxia-telangiectasia-related (atr) protein kinase.

SIGNOR-134716

Q13131

Q9Y478

1

phosphorylation

up-regulates

0.925

Mutation of serine 108 to alanine, an autophosphorylation site within the glycogen binding domain of the beta1 subunit, almost completely abolishes activation of ampk by a-769662 in cells and in vitro, while only partially reducing activation by amp

SIGNOR-157553

O95760

Q01638

1

binding

up-regulates activity

0.925

We report a member of the IL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T(H)2 cells. In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs.The binding of IL-33 to cells that express ST2 results in the activation of NF-κB and MAP kinases. Administration of purified IL-33 either in vitro or in vivo leads to the production of TH2-associated cytokines.

SIGNOR-277711

Q969D9

Q9HC73

1

binding

up-regulates

0.924

Human tslp is proposed to signal through a heterodimeric receptor complex that consists of a new member of the hemopoietin family termed human tslp receptor and the il-7r alpha-chain.

SIGNOR-108920

Q16552

Q96F46

1

binding

up-regulates

0.924

Binding studies suggest that recombinant hil-17 binds to the hil-17r with low affinity. Monoclonal antibodies (mabs) generated against the hil-17r were able to block the il-17-induced production of cytokine from human foreskin fibroblast (hff) cells.

SIGNOR-53249

O15123

Q02763

1

binding

up-regulates

0.924

Angiopoietin-1 and -2, bound to tek with similar affinities, and angiopoietin-1 effectively induced tek phosphorylation in hematopoietic cells. Angiopoietin-2 also induced a low level of tek phosphorylation and weakened the phosphorylation induced by angiopoietin-1

SIGNOR-59808

O43921

P54764

1

binding

up-regulates

0.924

Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor

SIGNOR-52203

Q12824

P51531

1

binding

up-regulates activity

0.924

The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added.

SIGNOR-65181

P01112

P42336

1

binding

up-regulates

0.924

In vivo, dominant negative ras mutant n17 inhibits growth factor induced production of 3' phosphorylated phosphoinositides in pc12 cells, and transfection of ras, but not raf, into cos cells results in a large elevation in the level of these lipids. Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. it was also described that ras interacts with pi3k in a direct manner. lysine residue 227 is essential for the interaction of ras with pi3k

SIGNOR-35878

P01236

P16471

1

binding

up-regulates

0.924

Prolactin-dependent signaling occurs as the result of ligand-induced dimerization of the prolactin receptor (prlr).

SIGNOR-72810

Q15835

P08100

1

phosphorylation

up-regulates activity

0.923

That light-dependent phosphorylation of Rho is mediated primarily by RK. Addition of an inhibitory antibody against rhodopsin kinase (RK) lowered phosphorylation at Ser334, Ser338, and Ser343, without changing the ratio between phosphorylation sites. upon illumination, Ser334c, Ser338, and Ser343 are phosphorylated.

SIGNOR-251190

P00533

P62993

1

binding

up-regulates activity

0.923

Adaptor protein Grb2 binds phosphotyrosines in the epidermal growth factor (EGF) receptor (EGFR) and thereby links receptor activation to intracellular signaling cascades.

SIGNOR-267725

Q92585

P46531

1

binding

up-regulates

0.923

Maml1 binds to the ankyrin repeat domain of all four mammalian notch receptors, forms a dna-binding complex with icn and rbp-jkappa, and amplifies notch-induced transcription of hes1.Maml1 functions as a transcriptional co-activator for notch signalling.

SIGNOR-86117

Q96BI3

P49810

1

binding

up-regulates

0.923

Gamma secretase subunit. Leads to ps1/ps2 eterodimer complex stabilisation. By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain.

SIGNOR-93265

Q9UJ41

P20339

1

binding

up-regulates

0.923

We have previously shown that rab5, which regulates various steps of transport along the early endocytic pathway, is activated by a complex consisting of rabex-5, a rab5 nucleotide exchange factor, and the effector rabaptin-5.

SIGNOR-109398

P12931

O60716

1

phosphorylation

up-regulates activity

0.922

Identification of Src phosphorylation sites in the catenin p120ctn.Using selected tyrosine to phenylalanine p120 mutants as dominant negative reagents, it may now be possible to selectively block events postulated to be dependent on p120 tyrosine phosphorylation.combinations of Tyr _ Phe mutations at residues 96, 112, 228, 257, 280, 291, 296, and 302

SIGNOR-246484

P98170

P55211

1

binding

down-regulates quantity by destabilization

0.922

A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis

SIGNOR-105702

P53350

P14635

1

phosphorylation

up-regulates activity

0.922

Phosphorylation of cyclin b1 is central to its nuclear translocationduring cell-cycle progression in hela cells, a change in the kinase activity of endogenous plk1 toward s147 and/or s133 correlates with a kinase activity in the cell extractsa mutant cyclin b1 in which s133 and s147 are replaced by alanines remains in the cytoplasm, whereas wild-type cyclin b1 accumulates in the nucleus during prophase.Together, these results suggest that phosphorylation of s133 and s147 is necessary for the nuclear translocation of cyclin b1 during prophase, and that phosphorylation of s126 and s128 may stimulate the nuclear translocation.

SIGNOR-105719

P52803

P29317

1

binding

up-regulates

0.922

Members of the epha subfamily of receptor tyrosine kinases and their ephrin-a ligands have been implicated in the guidance of retinal axons along the anterior-posterior axis of the chick optic tectum.

SIGNOR-52467

O14920

P25963

1

phosphorylation

down-regulates activity

0.922

Tak1 become activated and then phosphorilates and activates ikk2 which in turn now phosphorylates ikba, marking it for k48-ubiquitination and proteasomal degradation

SIGNOR-235400

P61764

Q16623

1

binding

up-regulates activity

0.922

Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis. We have now identified two Munc18-1-interacting proteins called Mint1 and Mint2 that may mediate the function of Munc18-1.

SIGNOR-264042

P49815

Q15382

1

gtpase-activating protein

down-regulates activity

0.922

Tsc2 functions as a gap to inhibit rheb activity. Tsc2 displays gap (gtpase-activating protein) activity specifically towards the small g protein rheb and inhibits its ability to stimulate the mtor signaling pathway. It has recently been shown that tsc2 has gtpase-activating protein (gap) activity towards the ras family small gtpase rheb (ras homolog enriched in brain), and tsc1/2 antagonizes the mtor signaling pathway via stimulation of gtp hydrolysis of rheb.

SIGNOR-128432

Q99836

Q9Y4K3

1

binding

up-regulates activity

0.922

In innate immunity, nearly all Toll-like receptors (TLRs), as well as the receptors of the interleukin 1 (IL-1) family of cytokines, initiate signaling by recruiting the adaptor protein MyD88. This is followed by the interaction of IL-1-receptor (IL-R)-associated kinase 4 (IRAK4) with MyD88 and then the interaction of other IRAK family members with IRAK4, to form an oligomeric complex, termed the Myddosome (8, 9). IRAK1 and IRAK2 can then interact with TRAF6 (10, 11) and induce TRAF6 dimerization (12), which triggers the activation of its E3 ligase activity

SIGNOR-260160

P20701

P05362

1

binding

up-regulates

0.922

This leads to further neutrophil-endothelial cell interactions through the binding of LFA-1 to its endothelial counterreceptor ICAM-1 during the slow rolling phase

SIGNOR-255040

P06400

Q01094

1

binding

down-regulates activity

0.921

E2f binds rb. E2f activation domain is the target for rb-induced repression. Rb can silence the 57 residue e2f activation domain. Rb can mask e2f residues involved in the activation process, possibly by mimicking a component of the transcriptional machinery

SIGNOR-37305

P23510

P43489

1

binding

up-regulates

0.921

Activation of nf-kappab in ox40-transfected hsb-2 cells was detected by electrophoretic mobility shift assay within 30 min after the binding of the ligand gp34.

SIGNOR-54927

P13984

P19388

1

binding

up-regulates activity

0.921

Direct Interaction Between the Subunit RAP30 of Transcription Factor IIF (TFIIF) and RNA Polymerase Subunit 5, Which Contributes to the Association Between TFIIF and RNA Polymerase II. we showed that RPB5 binds RAP30 but not RAP74 and associates to TFIIF through the binding to RAP30.

SIGNOR-261179

Q00978

P52630

1

binding

up-regulates activity

0.921

Coimmunoprecipitation assays demonstrate p48 association with STAT2 but not STAT1.The studies demonstrate the in vivo existence of a STAT2.p48 complex and a distinct STAT2.STAT1 complex after IFN-alpha stimulation. Data suggest that distinct bipartite complexes STAT2.p48 and STAT2.STAT1 translocate to the nucleus and associate on the DNA target site as ISGF3.

SIGNOR-217806

Q7L9L4

O95835

1

binding

up-regulates

0.921

Lats1/2 are activated by association with the highly homologous scaffold proteins mps one binder kinase activator-like 1a (mobkl1a) and 1b (mobkl1b), which are collectively referred to as mob1.

SIGNOR-169795

O43791

Q13618

1

binding

up-regulates activity

0.921

Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127.

SIGNOR-268927