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0 | PMID-10085159 | [
{
"id": "PMID-10085159__text",
"type": "abstract",
"text": [
"The Cdc6 protein is ubiquitinated in vivo for proteolysis in Saccharomyces cerevisiae. \nThe Saccharomyces cerevisiae Cdc6 protein is necessary for the formation of pre-replicative complexes that are required for firing DNA replication at origins at the beginning of S phase. Cdc6p protein levels oscillate during the cell cycle. In a normal cell cycle the presence of this protein is restricted to G1, partly because the CDC6 gene is transcribed only during G1 and partly because the Cdc6p protein is rapidly degraded at late G1/early S phase. We report here that the Cdc6p protein is degraded in a Cdc4-dependent manner, suggesting that phosphorylated Cdc6 is specifically recognized by the ubiquitin-mediated proteolysis machinery. Indeed, we have found that Cdc6 is ubiquitinated in vivo and degraded by a Cdc4-dependent mechanism. Our data, together with previous observations regarding Cdc6 stability, suggest that under physiological conditions budding yeast cells degrade ubiquitinated Cdc6 every cell cycle at the beginning of S phase.\n"
],
"offsets": [
[
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}
] | [
{
"id": "PMID-10085159_T1",
"type": "Gene_or_gene_product",
"offsets": [
[
4,
8
]
],
"text": [
"Cdc6"
],
"normalized": []
},
{
"id": "PMID-10085159_T2",
"type": "Gene_or_gene_product",
"offsets": [
[
117,
121
]
],
"text": [
"Cdc6"
],
"normalized": []
},
{
"id": "PMID-10085159_T3",
"type": "Complex",
"offsets": [
[
164,
189
]
],
"text": [
"pre-replicative complexes"
],
"normalized": []
},
{
"id": "PMID-10085159_T4",
"type": "Gene_or_gene_product",
"offsets": [
[
275,
280
]
],
"text": [
"Cdc6p"
],
"normalized": []
},
{
"id": "PMID-10085159_T5",
"type": "Gene_or_gene_product",
"offsets": [
[
421,
425
]
],
"text": [
"CDC6"
],
"normalized": []
},
{
"id": "PMID-10085159_T6",
"type": "Gene_or_gene_product",
"offsets": [
[
484,
489
]
],
"text": [
"Cdc6p"
],
"normalized": []
},
{
"id": "PMID-10085159_T7",
"type": "Gene_or_gene_product",
"offsets": [
[
568,
573
]
],
"text": [
"Cdc6p"
],
"normalized": []
},
{
"id": "PMID-10085159_T8",
"type": "Gene_or_gene_product",
"offsets": [
[
599,
603
]
],
"text": [
"Cdc4"
],
"normalized": []
},
{
"id": "PMID-10085159_T9",
"type": "Gene_or_gene_product",
"offsets": [
[
653,
657
]
],
"text": [
"Cdc6"
],
"normalized": []
},
{
"id": "PMID-10085159_T10",
"type": "Gene_or_gene_product",
"offsets": [
[
692,
701
]
],
"text": [
"ubiquitin"
],
"normalized": []
},
{
"id": "PMID-10085159_T11",
"type": "Gene_or_gene_product",
"offsets": [
[
761,
765
]
],
"text": [
"Cdc6"
],
"normalized": []
},
{
"id": "PMID-10085159_T12",
"type": "Gene_or_gene_product",
"offsets": [
[
809,
813
]
],
"text": [
"Cdc4"
],
"normalized": []
},
{
"id": "PMID-10085159_T13",
"type": "Gene_or_gene_product",
"offsets": [
[
891,
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]
],
"text": [
"Cdc6"
],
"normalized": []
},
{
"id": "PMID-10085159_T14",
"type": "Gene_or_gene_product",
"offsets": [
[
993,
997
]
],
"text": [
"Cdc6"
],
"normalized": []
}
] | [
{
"id": "PMID-10085159_E1",
"type": "Ubiquitination",
"trigger": {
"text": [
"ubiquitinated"
],
"offsets": [
[
20,
33
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10085159_T1"
}
]
},
{
"id": "PMID-10085159_E2",
"type": "Degradation",
"trigger": {
"text": [
"proteolysis"
],
"offsets": [
[
46,
57
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10085159_T1"
}
]
},
{
"id": "PMID-10085159_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"necessary"
],
"offsets": [
[
133,
142
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10085159_E4"
},
{
"role": "Cause",
"ref_id": "PMID-10085159_T2"
}
]
},
{
"id": "PMID-10085159_E4",
"type": "Binding",
"trigger": {
"text": [
"formation"
],
"offsets": [
[
151,
160
]
]
},
"arguments": [
{
"role": "Product",
"ref_id": "PMID-10085159_T3"
}
]
},
{
"id": "PMID-10085159_E5",
"type": "Regulation",
"trigger": {
"text": [
"oscillate"
],
"offsets": [
[
296,
305
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10085159_T4"
},
{
"role": "Cause",
"ref_id": "PMID-10085159_E6"
}
]
},
{
"id": "PMID-10085159_E6",
"type": "Pathway",
"trigger": {
"text": [
"cell cycl"
],
"offsets": [
[
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326
]
]
},
"arguments": []
},
{
"id": "PMID-10085159_E7",
"type": "Transcription",
"trigger": {
"text": [
"transcribed"
],
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10085159_T5"
}
]
},
{
"id": "PMID-10085159_E8",
"type": "Degradation",
"trigger": {
"text": [
"degraded"
],
"offsets": [
[
509,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10085159_T6"
}
]
},
{
"id": "PMID-10085159_E9",
"type": "Degradation",
"trigger": {
"text": [
"degraded"
],
"offsets": [
[
585,
593
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10085159_T7"
}
]
},
{
"id": "PMID-10085159_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"dependent"
],
"offsets": [
[
604,
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]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10085159_T8"
},
{
"role": "Theme",
"ref_id": "PMID-10085159_E9"
}
]
},
{
"id": "PMID-10085159_E11",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
638,
652
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10085159_T9"
}
]
},
{
"id": "PMID-10085159_E12",
"type": "Ubiquitination",
"trigger": {
"text": [
"ubiquitinated"
],
"offsets": [
[
769,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10085159_T11"
}
]
},
{
"id": "PMID-10085159_E13",
"type": "Degradation",
"trigger": {
"text": [
"degraded"
],
"offsets": [
[
795,
803
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10085159_T11"
}
]
},
{
"id": "PMID-10085159_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"dependent"
],
"offsets": [
[
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]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10085159_T12"
},
{
"role": "Theme",
"ref_id": "PMID-10085159_E13"
}
]
},
{
"id": "PMID-10085159_E15",
"type": "Degradation",
"trigger": {
"text": [
"degrade"
],
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]
]
},
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{
"role": "Theme",
"ref_id": "PMID-10085159_T14"
}
]
},
{
"id": "PMID-10085159_E16",
"type": "Ubiquitination",
"trigger": {
"text": [
"ubiquitinated"
],
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[
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10085159_T14"
}
]
},
{
"id": "PMID-10085159_E17",
"type": "Pathway",
"trigger": {
"text": [
"cell cycle"
],
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]
]
},
"arguments": []
},
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"id": "PMID-10085159_E18",
"type": "Pathway",
"trigger": {
"text": [
"cell cycle"
],
"offsets": [
[
341,
351
]
]
},
"arguments": []
}
] | [] | [] |
1 | PMID-10224130 | [
{
"id": "PMID-10224130__text",
"type": "abstract",
"text": [
"Regulation of NF-kappaB RelA phosphorylation and transcriptional activity by p21(ras) and protein kinase Czeta in primary endothelial cells. \nThe activity of the transcription factor NF-kappaB is thought to be regulated mainly through cytoplasmic retention by IkappaB molecules. Here we present evidence of a second mechanism of regulation acting on NF-kappaB after release from IkappaB. In endothelial cells this mechanism involves phosphorylation of the RelA subunit of NF-kappaB through a pathway involving activation of protein kinase Czeta (PKCzeta) and p21(ras). We show that transcriptional activity of RelA is dependent on phosphorylation of the N-terminal Rel homology domain but not the C-terminal transactivation domain. Inhibition of phosphorylation by dominant negative mutants of PKCzeta or p21(ras) results in loss of RelA transcriptional activity without interfering with DNA binding. Raf/MEK, small GTPases, phosphatidylinositol 3-kinase, and stress-activated protein kinase pathways are not involved in this mechanism of regulation.\n"
],
"offsets": [
[
0,
1051
]
]
}
] | [
{
"id": "PMID-10224130_T1",
"type": "Complex",
"offsets": [
[
14,
23
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10224130_T2",
"type": "Gene_or_gene_product",
"offsets": [
[
24,
28
]
],
"text": [
"RelA"
],
"normalized": []
},
{
"id": "PMID-10224130_T3",
"type": "Gene_or_gene_product",
"offsets": [
[
77,
80
]
],
"text": [
"p21"
],
"normalized": []
},
{
"id": "PMID-10224130_T4",
"type": "Gene_or_gene_product",
"offsets": [
[
81,
84
]
],
"text": [
"ras"
],
"normalized": []
},
{
"id": "PMID-10224130_T5",
"type": "Gene_or_gene_product",
"offsets": [
[
90,
110
]
],
"text": [
"protein kinase Czeta"
],
"normalized": []
},
{
"id": "PMID-10224130_T6",
"type": "Complex",
"offsets": [
[
183,
192
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10224130_T7",
"type": "Cellular_component",
"offsets": [
[
235,
246
]
],
"text": [
"cytoplasmic"
],
"normalized": []
},
{
"id": "PMID-10224130_T8",
"type": "Gene_or_gene_product",
"offsets": [
[
260,
267
]
],
"text": [
"IkappaB"
],
"normalized": []
},
{
"id": "PMID-10224130_T9",
"type": "Complex",
"offsets": [
[
350,
359
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10224130_T10",
"type": "Gene_or_gene_product",
"offsets": [
[
379,
386
]
],
"text": [
"IkappaB"
],
"normalized": []
},
{
"id": "PMID-10224130_T11",
"type": "Gene_or_gene_product",
"offsets": [
[
456,
460
]
],
"text": [
"RelA"
],
"normalized": []
},
{
"id": "PMID-10224130_T12",
"type": "Complex",
"offsets": [
[
472,
481
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10224130_T13",
"type": "Gene_or_gene_product",
"offsets": [
[
524,
544
]
],
"text": [
"protein kinase Czeta"
],
"normalized": []
},
{
"id": "PMID-10224130_T14",
"type": "Gene_or_gene_product",
"offsets": [
[
546,
553
]
],
"text": [
"PKCzeta"
],
"normalized": []
},
{
"id": "PMID-10224130_T15",
"type": "Gene_or_gene_product",
"offsets": [
[
559,
562
]
],
"text": [
"p21"
],
"normalized": []
},
{
"id": "PMID-10224130_T16",
"type": "Gene_or_gene_product",
"offsets": [
[
563,
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]
],
"text": [
"ras"
],
"normalized": []
},
{
"id": "PMID-10224130_T17",
"type": "Gene_or_gene_product",
"offsets": [
[
610,
614
]
],
"text": [
"RelA"
],
"normalized": []
},
{
"id": "PMID-10224130_T18",
"type": "Gene_or_gene_product",
"offsets": [
[
665,
668
]
],
"text": [
"Rel"
],
"normalized": []
},
{
"id": "PMID-10224130_T19",
"type": "Gene_or_gene_product",
"offsets": [
[
794,
801
]
],
"text": [
"PKCzeta"
],
"normalized": []
},
{
"id": "PMID-10224130_T20",
"type": "Gene_or_gene_product",
"offsets": [
[
805,
808
]
],
"text": [
"p21"
],
"normalized": []
},
{
"id": "PMID-10224130_T21",
"type": "Gene_or_gene_product",
"offsets": [
[
809,
812
]
],
"text": [
"ras"
],
"normalized": []
},
{
"id": "PMID-10224130_T22",
"type": "Gene_or_gene_product",
"offsets": [
[
833,
837
]
],
"text": [
"RelA"
],
"normalized": []
},
{
"id": "PMID-10224130_T23",
"type": "Gene_or_gene_product",
"offsets": [
[
901,
904
]
],
"text": [
"Raf"
],
"normalized": []
},
{
"id": "PMID-10224130_T24",
"type": "Gene_or_gene_product",
"offsets": [
[
905,
908
]
],
"text": [
"MEK"
],
"normalized": []
},
{
"id": "PMID-10224130_T25",
"type": "Gene_or_gene_product",
"offsets": [
[
925,
954
]
],
"text": [
"phosphatidylinositol 3-kinase"
],
"normalized": []
},
{
"id": "PMID-10224130_T26",
"type": "Gene_or_gene_product",
"offsets": [
[
960,
991
]
],
"text": [
"stress-activated protein kinase"
],
"normalized": []
}
] | [
{
"id": "PMID-10224130_E1",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
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{
"role": "Cause",
"ref_id": "PMID-10224130_T4"
},
{
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"ref_id": "PMID-10224130_E7"
}
]
},
{
"id": "PMID-10224130_E2",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
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{
"role": "Cause",
"ref_id": "PMID-10224130_T5"
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{
"role": "Theme",
"ref_id": "PMID-10224130_E7"
}
]
},
{
"id": "PMID-10224130_E3",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10224130_T5"
},
{
"role": "Theme",
"ref_id": "PMID-10224130_E8"
}
]
},
{
"id": "PMID-10224130_E4",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10224130_T4"
},
{
"role": "Theme",
"ref_id": "PMID-10224130_E8"
}
]
},
{
"id": "PMID-10224130_E5",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10224130_E9"
},
{
"role": "Cause",
"ref_id": "PMID-10224130_T4"
}
]
},
{
"id": "PMID-10224130_E6",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10224130_E9"
},
{
"role": "Cause",
"ref_id": "PMID-10224130_T5"
}
]
},
{
"id": "PMID-10224130_E7",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
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[
29,
44
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10224130_T1"
}
]
},
{
"id": "PMID-10224130_E8",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
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[
29,
44
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10224130_T2"
}
]
},
{
"id": "PMID-10224130_E9",
"type": "Transcription",
"trigger": {
"text": [
"transcriptional"
],
"offsets": [
[
49,
64
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10224130_T2"
}
]
},
{
"id": "PMID-10224130_E10",
"type": "Regulation",
"trigger": {
"text": [
"regulated"
],
"offsets": [
[
210,
219
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10224130_T6"
},
{
"role": "Cause",
"ref_id": "PMID-10224130_E11"
}
]
},
{
"id": "PMID-10224130_E11",
"type": "Localization",
"trigger": {
"text": [
"retention"
],
"offsets": [
[
247,
256
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-10224130_T7"
},
{
"role": "Theme",
"ref_id": "PMID-10224130_T6"
}
]
},
{
"id": "PMID-10224130_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"retention"
],
"offsets": [
[
247,
256
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10224130_E11"
},
{
"role": "Cause",
"ref_id": "PMID-10224130_T8"
}
]
},
{
"id": "PMID-10224130_E13",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
329,
339
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10224130_T9"
}
]
},
{
"id": "PMID-10224130_E14",
"type": "Dissociation",
"trigger": {
"text": [
"release"
],
"offsets": [
[
366,
373
]
]
},
"arguments": [
{
"role": "Product",
"ref_id": "PMID-10224130_T9"
}
]
},
{
"id": "PMID-10224130_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"involves"
],
"offsets": [
[
424,
432
]
]
},
"arguments": [
{
"role": "Theme",
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},
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"ref_id": "PMID-10224130_E17"
}
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"text": [
"phosphorylation"
],
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448
]
]
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"role": "Theme",
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}
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}
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],
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500,
509
]
]
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}
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500,
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}
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510,
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"text": [
"phosphorylation"
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"role": "Theme",
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"role": "Theme",
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},
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}
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"loss"
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825,
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]
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"role": "Theme",
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}
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},
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"transcriptional"
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"role": "Theme",
"ref_id": "PMID-10224130_T22"
}
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]
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"role": "Cause",
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},
{
"role": "Participant",
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}
]
}
] | [
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]
}
] | [] |
2 | PMID-10329026 | [
{
"id": "PMID-10329026__text",
"type": "abstract",
"text": [
"Cloning and characterization of retinol dehydrogenase transcripts expressed in human epidermal keratinocytes. \nThe normal growth and differentiation of the epidermis require an adequate supply of vitamin A. The active form of vitamin A for normal epidermal homeostasis is retinoic acid (RA). Retinoic acid controls the expression of retinoid-responsive genes via interactions of the retinoic acid/nuclear receptor complexes at specific DNA sequences in their control regions. The message conveyed by RA is likely modulated by the concentration of the ligand available for binding to the receptors. Following the uptake of plasma retinol, epidermal keratinocytes synthesize retinoic acid via two sequential reactions with retinaldehyde as an intermediate. Several retinol dehydrogenase (RDH) enzymes, members of the short-chain dehydrogenase/reductase (SDR) gene superfamily, catalyze the first and rate-limiting step that generates retinaldehyde from retinol bound to cellular retinol-binding protein (holo-CRBP). However, little is known about these enzymes and their genes in the epidermal cells. Our work describes the first member of the RDH family found in epidermis. We show that this gene is expressed predominantly in the differentiating spinous layers and that it is under positive, feed-forward regulation by retinoic acid. It encodes a protein that, using NAD+ as a preferred cofactor, utilizes free and CRBP-bound all-trans-retinol and steroids as substrates.\n"
],
"offsets": [
[
0,
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]
]
}
] | [
{
"id": "PMID-10329026_T1",
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[
32,
53
]
],
"text": [
"retinol dehydrogenase"
],
"normalized": []
},
{
"id": "PMID-10329026_T2",
"type": "Simple_chemical",
"offsets": [
[
196,
205
]
],
"text": [
"vitamin A"
],
"normalized": []
},
{
"id": "PMID-10329026_T3",
"type": "Simple_chemical",
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226,
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"text": [
"vitamin A"
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},
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"id": "PMID-10329026_T4",
"type": "Simple_chemical",
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272,
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]
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"text": [
"retinoic acid"
],
"normalized": []
},
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"id": "PMID-10329026_T5",
"type": "Simple_chemical",
"offsets": [
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287,
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]
],
"text": [
"RA"
],
"normalized": []
},
{
"id": "PMID-10329026_T6",
"type": "Simple_chemical",
"offsets": [
[
292,
305
]
],
"text": [
"Retinoic acid"
],
"normalized": []
},
{
"id": "PMID-10329026_T7",
"type": "Simple_chemical",
"offsets": [
[
333,
341
]
],
"text": [
"retinoid"
],
"normalized": []
},
{
"id": "PMID-10329026_T8",
"type": "Complex",
"offsets": [
[
383,
413
]
],
"text": [
"retinoic acid/nuclear receptor"
],
"normalized": []
},
{
"id": "PMID-10329026_T9",
"type": "Simple_chemical",
"offsets": [
[
500,
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]
],
"text": [
"RA"
],
"normalized": []
},
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"id": "PMID-10329026_T10",
"type": "Simple_chemical",
"offsets": [
[
629,
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]
],
"text": [
"retinol"
],
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},
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"id": "PMID-10329026_T11",
"type": "Simple_chemical",
"offsets": [
[
673,
686
]
],
"text": [
"retinoic acid"
],
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},
{
"id": "PMID-10329026_T12",
"type": "Simple_chemical",
"offsets": [
[
721,
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]
],
"text": [
"retinaldehyde"
],
"normalized": []
},
{
"id": "PMID-10329026_T13",
"type": "Gene_or_gene_product",
"offsets": [
[
763,
784
]
],
"text": [
"retinol dehydrogenase"
],
"normalized": []
},
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"id": "PMID-10329026_T14",
"type": "Gene_or_gene_product",
"offsets": [
[
786,
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]
],
"text": [
"RDH"
],
"normalized": []
},
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"id": "PMID-10329026_T15",
"type": "Gene_or_gene_product",
"offsets": [
[
815,
850
]
],
"text": [
"short-chain dehydrogenase/reductase"
],
"normalized": []
},
{
"id": "PMID-10329026_T16",
"type": "Gene_or_gene_product",
"offsets": [
[
852,
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]
],
"text": [
"SDR"
],
"normalized": []
},
{
"id": "PMID-10329026_T17",
"type": "Simple_chemical",
"offsets": [
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]
],
"text": [
"retinaldehyde"
],
"normalized": []
},
{
"id": "PMID-10329026_T18",
"type": "Simple_chemical",
"offsets": [
[
951,
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]
],
"text": [
"retinol"
],
"normalized": []
},
{
"id": "PMID-10329026_T19",
"type": "Gene_or_gene_product",
"offsets": [
[
968,
1000
]
],
"text": [
"cellular retinol-binding protein"
],
"normalized": []
},
{
"id": "PMID-10329026_T20",
"type": "Gene_or_gene_product",
"offsets": [
[
1007,
1011
]
],
"text": [
"CRBP"
],
"normalized": []
},
{
"id": "PMID-10329026_T21",
"type": "Gene_or_gene_product",
"offsets": [
[
1142,
1145
]
],
"text": [
"RDH"
],
"normalized": []
},
{
"id": "PMID-10329026_T22",
"type": "Simple_chemical",
"offsets": [
[
1319,
1332
]
],
"text": [
"retinoic acid"
],
"normalized": []
},
{
"id": "PMID-10329026_T23",
"type": "Simple_chemical",
"offsets": [
[
1367,
1371
]
],
"text": [
"NAD+"
],
"normalized": []
},
{
"id": "PMID-10329026_T24",
"type": "Gene_or_gene_product",
"offsets": [
[
1415,
1419
]
],
"text": [
"CRBP"
],
"normalized": []
},
{
"id": "PMID-10329026_T25",
"type": "Simple_chemical",
"offsets": [
[
1426,
1443
]
],
"text": [
"all-trans-retinol"
],
"normalized": []
}
] | [
{
"id": "PMID-10329026_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
66,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10329026_T1"
}
]
},
{
"id": "PMID-10329026_E2",
"type": "Activation",
"trigger": {
"text": [
"active"
],
"offsets": [
[
211,
217
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10329026_T3"
}
]
},
{
"id": "PMID-10329026_E3",
"type": "Binding",
"trigger": {
"text": [
"interactions"
],
"offsets": [
[
363,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10329026_T8"
}
]
},
{
"id": "PMID-10329026_E4",
"type": "Transport",
"trigger": {
"text": [
"uptake"
],
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[
612,
618
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10329026_T10"
}
]
},
{
"id": "PMID-10329026_E5",
"type": "Conversion",
"trigger": {
"text": [
"synthesize"
],
"offsets": [
[
662,
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]
]
},
"arguments": [
{
"role": "Product",
"ref_id": "PMID-10329026_T11"
}
]
},
{
"id": "PMID-10329026_E6",
"type": "Conversion",
"trigger": {
"text": [
"generates"
],
"offsets": [
[
922,
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]
]
},
"arguments": [
{
"role": "Product",
"ref_id": "PMID-10329026_T17"
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"role": "Theme",
"ref_id": "PMID-10329026_T18"
}
]
},
{
"id": "PMID-10329026_E7",
"type": "Binding",
"trigger": {
"text": [
"bound"
],
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959,
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]
},
"arguments": [
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"role": "Theme",
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"role": "Theme",
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}
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"type": "Conversion",
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"text": [
"utilizes"
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},
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"role": "Theme",
"ref_id": "PMID-10329026_T25"
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},
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},
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"role": "Theme",
"ref_id": "PMID-10329026_T24"
},
{
"role": "Theme",
"ref_id": "PMID-10329026_T25"
}
]
}
] | [
{
"id": "PMID-10329026_1",
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"PMID-10329026_T5"
]
},
{
"id": "PMID-10329026_2",
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"PMID-10329026_T13",
"PMID-10329026_T14"
]
},
{
"id": "PMID-10329026_3",
"entity_ids": [
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"PMID-10329026_T16"
]
},
{
"id": "PMID-10329026_4",
"entity_ids": [
"PMID-10329026_T19",
"PMID-10329026_T20"
]
}
] | [] |
3 | PMID-10346818 | [
{
"id": "PMID-10346818__text",
"type": "abstract",
"text": [
"Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. \nInterleukin-1 (IL-1) and tumor necrosis factor (TNF-alpha) stimulate transcription factors AP-1 and NF-kappaB through activation of the MAP kinases JNK and p38 and the IkappaB kinase (IKK), respectively. The TNF-alpha and IL-1 signals are transduced through TRAF2 and TRAF6, respectively. Overexpressed TRAF2 or TRAF6 activate JNK, p38, or IKK in the absence of extracellular stimulation. By replacing the carboxy-terminal TRAF domain of TRAF2 and TRAF6 with repeats of the immunophilin FKBP12, we demonstrate that their effector domains are composed of their amino-terminal Zn and RING fingers. Oligomerization of the TRAF2 effector domain results in specific binding to MEKK1, a protein kinase capable of JNK, p38, and IKK activation, and induction of TNF-alpha and IL-1 responsive genes. TNF-alpha also enhances the binding of native TRAF2 to MEKK1 and stimulates the kinase activity of the latter. Thus, TNF-alpha and IL-1 signaling is based on oligomerization of TRAF2 and TRAF6 leading to activation of effector kinases.\n"
],
"offsets": [
[
0,
1209
]
]
}
] | [
{
"id": "PMID-10346818_T1",
"type": "Gene_or_gene_product",
"offsets": [
[
59,
64
]
],
"text": [
"TRAF2"
],
"normalized": []
},
{
"id": "PMID-10346818_T2",
"type": "Gene_or_gene_product",
"offsets": [
[
69,
74
]
],
"text": [
"TRAF6"
],
"normalized": []
},
{
"id": "PMID-10346818_T3",
"type": "Gene_or_gene_product",
"offsets": [
[
93,
96
]
],
"text": [
"JNK"
],
"normalized": []
},
{
"id": "PMID-10346818_T4",
"type": "Complex",
"offsets": [
[
101,
104
]
],
"text": [
"IKK"
],
"normalized": []
},
{
"id": "PMID-10346818_T5",
"type": "Gene_or_gene_product",
"offsets": [
[
182,
195
]
],
"text": [
"Interleukin-1"
],
"normalized": []
},
{
"id": "PMID-10346818_T6",
"type": "Gene_or_gene_product",
"offsets": [
[
197,
201
]
],
"text": [
"IL-1"
],
"normalized": []
},
{
"id": "PMID-10346818_T7",
"type": "Gene_or_gene_product",
"offsets": [
[
207,
228
]
],
"text": [
"tumor necrosis factor"
],
"normalized": []
},
{
"id": "PMID-10346818_T8",
"type": "Gene_or_gene_product",
"offsets": [
[
230,
239
]
],
"text": [
"TNF-alpha"
],
"normalized": []
},
{
"id": "PMID-10346818_T9",
"type": "Gene_or_gene_product",
"offsets": [
[
273,
277
]
],
"text": [
"AP-1"
],
"normalized": []
},
{
"id": "PMID-10346818_T10",
"type": "Complex",
"offsets": [
[
282,
291
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10346818_T11",
"type": "Gene_or_gene_product",
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[
318,
329
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],
"text": [
"MAP kinases"
],
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},
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"type": "Gene_or_gene_product",
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[
330,
333
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],
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],
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},
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"id": "PMID-10346818_T13",
"type": "Gene_or_gene_product",
"offsets": [
[
338,
341
]
],
"text": [
"p38"
],
"normalized": []
},
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350,
364
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366,
369
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390,
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440,
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450,
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485,
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509,
512
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514,
517
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522,
525
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544,
557
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605,
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620,
625
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630,
635
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669,
675
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757,
759
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801,
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859
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889,
892
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894,
897
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906
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945
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1024
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1028,
1033
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1099
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1155
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1165
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431
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}
] | [
{
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]
}
] | [] |
4 | PMID-10364168 | [
{
"id": "PMID-10364168__text",
"type": "abstract",
"text": [
"Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. \nThe life-threatening complications of sepsis in humans are elicited by infection with Gram-negative as well as Gram-positive bacteria. Recently, lipopolysaccharide (LPS), a major biologically active agent of Gram-negative bacteria, was shown to mediate cellular activation by a member of the human Toll-like receptor family, Toll-like receptor (TLR) 2. Here we investigate the mechanism of cellular activation by soluble peptidoglycan (sPGN) and lipoteichoic acid (LTA), main stimulatory components of Gram-positive bacteria. Like LPS, sPGN and LTA bind to the glycosylphosphatidylinositol-anchored membrane protein CD14 and induce activation of the transcription factor NF-kappaB in host cells like macrophages. We show that whole Gram-positive bacteria, sPGN and LTA induce the activation of NF-kappaB in HEK293 cells expressing TLR2 but not in cells expressing TLR1 or TLR4. The sPGN- and LTA-induced NF-kappaB activation was not inhibited by polymyxin B, an antibiotic that binds and neutralizes LPS. Coexpression together with membrane CD14 enhances sPGN signal transmission through TLR2. In contrast to LPS signaling, activation of TLR2 by sPGN and LTA does not require serum. These findings identify TLR2 as a signal transducer for sPGN and LTA in addition to LPS.\n"
],
"offsets": [
[
0,
1371
]
]
}
] | [
{
"id": "PMID-10364168_T1",
"type": "Simple_chemical",
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[
0,
13
]
],
"text": [
"Peptidoglycan"
],
"normalized": []
},
{
"id": "PMID-10364168_T2",
"type": "Simple_chemical",
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"text": [
"lipoteichoic acid"
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},
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"id": "PMID-10364168_T3",
"type": "Gene_or_gene_product",
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"text": [
"toll-like receptor 2"
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},
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"id": "PMID-10364168_T4",
"type": "Simple_chemical",
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244,
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"text": [
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},
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"id": "PMID-10364168_T5",
"type": "Simple_chemical",
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264,
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"LPS"
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},
{
"id": "PMID-10364168_T6",
"type": "Gene_or_gene_product",
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[
397,
415
]
],
"text": [
"Toll-like receptor"
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},
{
"id": "PMID-10364168_T7",
"type": "Gene_or_gene_product",
"offsets": [
[
424,
450
]
],
"text": [
"Toll-like receptor (TLR) 2"
],
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},
{
"id": "PMID-10364168_T8",
"type": "Simple_chemical",
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[
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],
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"peptidoglycan"
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},
{
"id": "PMID-10364168_T9",
"type": "Simple_chemical",
"offsets": [
[
535,
539
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],
"text": [
"sPGN"
],
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},
{
"id": "PMID-10364168_T10",
"type": "Simple_chemical",
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545,
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]
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"text": [
"lipoteichoic acid"
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},
{
"id": "PMID-10364168_T11",
"type": "Simple_chemical",
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564,
567
]
],
"text": [
"LTA"
],
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},
{
"id": "PMID-10364168_T12",
"type": "Simple_chemical",
"offsets": [
[
630,
633
]
],
"text": [
"LPS"
],
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},
{
"id": "PMID-10364168_T13",
"type": "Simple_chemical",
"offsets": [
[
635,
639
]
],
"text": [
"sPGN"
],
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},
{
"id": "PMID-10364168_T14",
"type": "Simple_chemical",
"offsets": [
[
644,
647
]
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"LTA"
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},
{
"id": "PMID-10364168_T15",
"type": "Simple_chemical",
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660,
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"text": [
"glycosylphosphatidylinositol"
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{
"id": "PMID-10364168_T17",
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"id": "PMID-10364168_T18",
"type": "Complex",
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770,
779
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},
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"id": "PMID-10364168_T19",
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"id": "PMID-10364168_T25",
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},
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994
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},
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"type": "Complex",
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1012
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},
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"id": "PMID-10364168_T28",
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1045,
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]
],
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"polymyxin B"
],
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},
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1099,
1102
]
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"LPS"
],
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},
{
"id": "PMID-10364168_T30",
"type": "Cellular_component",
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1131,
1139
]
],
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"membrane"
],
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},
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"id": "PMID-10364168_T31",
"type": "Gene_or_gene_product",
"offsets": [
[
1140,
1144
]
],
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"CD14"
],
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},
{
"id": "PMID-10364168_T32",
"type": "Simple_chemical",
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[
1154,
1158
]
],
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"sPGN"
],
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},
{
"id": "PMID-10364168_T33",
"type": "Gene_or_gene_product",
"offsets": [
[
1187,
1191
]
],
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"TLR2"
],
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},
{
"id": "PMID-10364168_T34",
"type": "Simple_chemical",
"offsets": [
[
1208,
1211
]
],
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"LPS"
],
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},
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"id": "PMID-10364168_T35",
"type": "Gene_or_gene_product",
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[
1237,
1241
]
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"TLR2"
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},
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"id": "PMID-10364168_T36",
"type": "Simple_chemical",
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[
1245,
1249
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},
{
"id": "PMID-10364168_T37",
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1254,
1257
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],
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"LTA"
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},
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"id": "PMID-10364168_T40",
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1347,
1350
]
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"LTA"
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"id": "PMID-10364168_T41",
"type": "Simple_chemical",
"offsets": [
[
1366,
1369
]
],
"text": [
"LPS"
],
"normalized": []
}
] | [
{
"id": "PMID-10364168_E1",
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"bind"
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"role": "Theme",
"ref_id": "PMID-10364168_T17"
}
]
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"role": "Theme",
"ref_id": "PMID-10364168_T14"
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{
"role": "Theme",
"ref_id": "PMID-10364168_T17"
}
]
},
{
"id": "PMID-10364168_E3",
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"induce"
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"role": "Theme",
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}
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"id": "PMID-10364168_E4",
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}
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},
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}
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},
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"ref_id": "PMID-10364168_E14"
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},
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"id": "PMID-10364168_E13",
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"role": "Theme",
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}
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},
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"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
1032,
1041
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10364168_T28"
},
{
"role": "Theme",
"ref_id": "PMID-10364168_E14"
}
]
},
{
"id": "PMID-10364168_E16",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
1077,
1082
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10364168_T28"
},
{
"role": "Theme",
"ref_id": "PMID-10364168_T29"
}
]
},
{
"id": "PMID-10364168_E17",
"type": "Negative_regulation",
"trigger": {
"text": [
"neutralizes"
],
"offsets": [
[
1087,
1098
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10364168_T28"
},
{
"role": "Theme",
"ref_id": "PMID-10364168_T29"
}
]
},
{
"id": "PMID-10364168_E18",
"type": "Gene_expression",
"trigger": {
"text": [
"Coexpression"
],
"offsets": [
[
1104,
1116
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10364168_T31"
}
]
},
{
"id": "PMID-10364168_E19",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhances"
],
"offsets": [
[
1145,
1153
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10364168_T33"
},
{
"role": "Theme",
"ref_id": "PMID-10364168_E18"
}
]
},
{
"id": "PMID-10364168_E20",
"type": "Activation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
1223,
1233
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10364168_T35"
},
{
"role": "Cause",
"ref_id": "PMID-10364168_T36"
}
]
},
{
"id": "PMID-10364168_E21",
"type": "Activation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
1223,
1233
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10364168_T35"
},
{
"role": "Cause",
"ref_id": "PMID-10364168_T37"
}
]
},
{
"id": "PMID-10364168_E22",
"type": "Positive_regulation",
"trigger": {
"text": [
"signal transducer"
],
"offsets": [
[
1316,
1333
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10364168_T38"
},
{
"role": "Theme",
"ref_id": "PMID-10364168_T39"
}
]
},
{
"id": "PMID-10364168_E23",
"type": "Positive_regulation",
"trigger": {
"text": [
"signal transducer"
],
"offsets": [
[
1316,
1333
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10364168_T38"
},
{
"role": "Theme",
"ref_id": "PMID-10364168_T40"
}
]
},
{
"id": "PMID-10364168_E24",
"type": "Positive_regulation",
"trigger": {
"text": [
"signal transducer"
],
"offsets": [
[
1316,
1333
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10364168_T38"
},
{
"role": "Theme",
"ref_id": "PMID-10364168_T41"
}
]
}
] | [
{
"id": "PMID-10364168_1",
"entity_ids": [
"PMID-10364168_T4",
"PMID-10364168_T5"
]
},
{
"id": "PMID-10364168_2",
"entity_ids": [
"PMID-10364168_T8",
"PMID-10364168_T9"
]
},
{
"id": "PMID-10364168_3",
"entity_ids": [
"PMID-10364168_T10",
"PMID-10364168_T11"
]
}
] | [] |
5 | PMID-10369669 | [
{
"id": "PMID-10369669__text",
"type": "abstract",
"text": [
"Glycoprotein reglucosylation and nucleotide sugar utilization in the secretory pathway: identification of a nucleoside diphosphatase in the endoplasmic reticulum. \nUDP is generated in the lumen of the endoplasmic reticulum (ER) as a product of the UDP-glucose-dependent glycoprotein reglucosylation in the calnexin/calreticulin cycle. We describe here the identification, purification and characterization of an ER enzyme that hydrolyzes UDP to UMP. This nucleoside diphosphatase is a ubiquitously expressed, soluble 45 kDa glycoprotein devoid of transmembrane domains and KDEL-related ER localization sequences. It requires divalent cations for activity and hydrolyzes UDP, GDP and IDP but not any other nucleoside di-, mono- or triphosphates, nor thiamine pyrophosphate. By eliminating UDP, which is an inhibitory product of the UDP-Glc:glycoprotein glucosyltransferase, it is likely to promote reglucosylation reactions involved in glycoprotein folding and quality control in the ER.\n"
],
"offsets": [
[
0,
987
]
]
}
] | [
{
"id": "PMID-10369669_T1",
"type": "Gene_or_gene_product",
"offsets": [
[
108,
132
]
],
"text": [
"nucleoside diphosphatase"
],
"normalized": []
},
{
"id": "PMID-10369669_T2",
"type": "Cellular_component",
"offsets": [
[
140,
161
]
],
"text": [
"endoplasmic reticulum"
],
"normalized": []
},
{
"id": "PMID-10369669_T3",
"type": "Simple_chemical",
"offsets": [
[
164,
167
]
],
"text": [
"UDP"
],
"normalized": []
},
{
"id": "PMID-10369669_T4",
"type": "Cellular_component",
"offsets": [
[
188,
193
]
],
"text": [
"lumen"
],
"normalized": []
},
{
"id": "PMID-10369669_T5",
"type": "Cellular_component",
"offsets": [
[
201,
222
]
],
"text": [
"endoplasmic reticulum"
],
"normalized": []
},
{
"id": "PMID-10369669_T6",
"type": "Cellular_component",
"offsets": [
[
224,
226
]
],
"text": [
"ER"
],
"normalized": []
},
{
"id": "PMID-10369669_T7",
"type": "Simple_chemical",
"offsets": [
[
248,
259
]
],
"text": [
"UDP-glucose"
],
"normalized": []
},
{
"id": "PMID-10369669_T8",
"type": "Gene_or_gene_product",
"offsets": [
[
306,
314
]
],
"text": [
"calnexin"
],
"normalized": []
},
{
"id": "PMID-10369669_T9",
"type": "Gene_or_gene_product",
"offsets": [
[
315,
327
]
],
"text": [
"calreticulin"
],
"normalized": []
},
{
"id": "PMID-10369669_T10",
"type": "Cellular_component",
"offsets": [
[
412,
414
]
],
"text": [
"ER"
],
"normalized": []
},
{
"id": "PMID-10369669_T11",
"type": "Simple_chemical",
"offsets": [
[
438,
441
]
],
"text": [
"UDP"
],
"normalized": []
},
{
"id": "PMID-10369669_T12",
"type": "Simple_chemical",
"offsets": [
[
445,
448
]
],
"text": [
"UMP"
],
"normalized": []
},
{
"id": "PMID-10369669_T13",
"type": "Gene_or_gene_product",
"offsets": [
[
455,
479
]
],
"text": [
"nucleoside diphosphatase"
],
"normalized": []
},
{
"id": "PMID-10369669_T14",
"type": "Gene_or_gene_product",
"offsets": [
[
573,
577
]
],
"text": [
"KDEL"
],
"normalized": []
},
{
"id": "PMID-10369669_T15",
"type": "Cellular_component",
"offsets": [
[
586,
588
]
],
"text": [
"ER"
],
"normalized": []
},
{
"id": "PMID-10369669_T16",
"type": "Simple_chemical",
"offsets": [
[
625,
641
]
],
"text": [
"divalent cations"
],
"normalized": []
},
{
"id": "PMID-10369669_T17",
"type": "Simple_chemical",
"offsets": [
[
670,
673
]
],
"text": [
"UDP"
],
"normalized": []
},
{
"id": "PMID-10369669_T18",
"type": "Simple_chemical",
"offsets": [
[
675,
678
]
],
"text": [
"GDP"
],
"normalized": []
},
{
"id": "PMID-10369669_T19",
"type": "Simple_chemical",
"offsets": [
[
683,
686
]
],
"text": [
"IDP"
],
"normalized": []
},
{
"id": "PMID-10369669_T20",
"type": "Simple_chemical",
"offsets": [
[
705,
719
]
],
"text": [
"nucleoside di-"
],
"normalized": []
},
{
"id": "PMID-10369669_T21",
"type": "Simple_chemical",
"offsets": [
[
721,
726
]
],
"text": [
"mono-"
],
"normalized": []
},
{
"id": "PMID-10369669_T22",
"type": "Simple_chemical",
"offsets": [
[
730,
743
]
],
"text": [
"triphosphates"
],
"normalized": []
},
{
"id": "PMID-10369669_T23",
"type": "Simple_chemical",
"offsets": [
[
749,
771
]
],
"text": [
"thiamine pyrophosphate"
],
"normalized": []
},
{
"id": "PMID-10369669_T24",
"type": "Simple_chemical",
"offsets": [
[
788,
791
]
],
"text": [
"UDP"
],
"normalized": []
},
{
"id": "PMID-10369669_T25",
"type": "Simple_chemical",
"offsets": [
[
831,
838
]
],
"text": [
"UDP-Glc"
],
"normalized": []
},
{
"id": "PMID-10369669_T26",
"type": "Gene_or_gene_product",
"offsets": [
[
839,
871
]
],
"text": [
"glycoprotein glucosyltransferase"
],
"normalized": []
},
{
"id": "PMID-10369669_T27",
"type": "Cellular_component",
"offsets": [
[
983,
985
]
],
"text": [
"ER"
],
"normalized": []
}
] | [
{
"id": "PMID-10369669_E1",
"type": "Conversion",
"trigger": {
"text": [
"generated"
],
"offsets": [
[
171,
180
]
]
},
"arguments": [
{
"role": "Product",
"ref_id": "PMID-10369669_T3"
}
]
},
{
"id": "PMID-10369669_E2",
"type": "Pathway",
"trigger": {
"text": [
"cycle"
],
"offsets": [
[
328,
333
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-10369669_T8"
},
{
"role": "Participant",
"ref_id": "PMID-10369669_T9"
}
]
},
{
"id": "PMID-10369669_E3",
"type": "Conversion",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
427,
437
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10369669_T11"
},
{
"role": "Product",
"ref_id": "PMID-10369669_T12"
}
]
},
{
"id": "PMID-10369669_E4",
"type": "Ubiquitination",
"trigger": {
"text": [
"ubiquitously"
],
"offsets": [
[
485,
497
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10369669_T13"
}
]
},
{
"id": "PMID-10369669_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
498,
507
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10369669_T13"
}
]
},
{
"id": "PMID-10369669_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"requires"
],
"offsets": [
[
616,
624
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10369669_T13"
},
{
"role": "Cause",
"ref_id": "PMID-10369669_T16"
}
]
},
{
"id": "PMID-10369669_E7",
"type": "Conversion",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10369669_T17"
}
]
},
{
"id": "PMID-10369669_E8",
"type": "Conversion",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10369669_T20"
}
]
},
{
"id": "PMID-10369669_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10369669_T13"
},
{
"role": "Theme",
"ref_id": "PMID-10369669_E8"
}
]
},
{
"id": "PMID-10369669_E10",
"type": "Conversion",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10369669_T22"
}
]
},
{
"id": "PMID-10369669_E11",
"type": "Conversion",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10369669_T23"
}
]
},
{
"id": "PMID-10369669_E12",
"type": "Conversion",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10369669_T21"
}
]
},
{
"id": "PMID-10369669_E13",
"type": "Conversion",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10369669_T18"
}
]
},
{
"id": "PMID-10369669_E14",
"type": "Conversion",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10369669_T19"
}
]
},
{
"id": "PMID-10369669_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10369669_T13"
},
{
"role": "Theme",
"ref_id": "PMID-10369669_E7"
}
]
},
{
"id": "PMID-10369669_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10369669_T13"
},
{
"role": "Theme",
"ref_id": "PMID-10369669_E10"
}
]
},
{
"id": "PMID-10369669_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10369669_T13"
},
{
"role": "Theme",
"ref_id": "PMID-10369669_E11"
}
]
},
{
"id": "PMID-10369669_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10369669_T13"
},
{
"role": "Theme",
"ref_id": "PMID-10369669_E12"
}
]
},
{
"id": "PMID-10369669_E19",
"type": "Positive_regulation",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10369669_T13"
},
{
"role": "Theme",
"ref_id": "PMID-10369669_E13"
}
]
},
{
"id": "PMID-10369669_E20",
"type": "Positive_regulation",
"trigger": {
"text": [
"hydrolyzes"
],
"offsets": [
[
659,
669
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10369669_T13"
},
{
"role": "Theme",
"ref_id": "PMID-10369669_E14"
}
]
},
{
"id": "PMID-10369669_E21",
"type": "Negative_regulation",
"trigger": {
"text": [
"eliminating"
],
"offsets": [
[
776,
787
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10369669_T24"
},
{
"role": "Cause",
"ref_id": "PMID-10369669_T13"
}
]
},
{
"id": "PMID-10369669_E22",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitory"
],
"offsets": [
[
805,
815
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10369669_T24"
},
{
"role": "Theme",
"ref_id": "PMID-10369669_T26"
}
]
}
] | [
{
"id": "PMID-10369669_1",
"entity_ids": [
"PMID-10369669_T5",
"PMID-10369669_T6"
]
}
] | [] |
6 | PMID-10373560 | [
{
"id": "PMID-10373560__text",
"type": "abstract",
"text": [
"Overproduction of human Myt1 kinase induces a G2 cell cycle delay by interfering with the intracellular trafficking of Cdc2-cyclin B1 complexes. \nThe Myt1 protein kinase functions to negatively regulate Cdc2-cyclin B complexes by phosphorylating Cdc2 on threonine 14 and tyrosine 15. Throughout interphase, human Myt1 localizes to the endoplasmic reticulum and Golgi complex, whereas Cdc2-cyclin B1 complexes shuttle between the nucleus and the cytoplasm. Here we report that overproduction of either kinase-active or kinase-inactive forms of Myt1 blocked the nuclear-cytoplasmic shuttling of cyclin B1 and caused cells to delay in the G2 phase of the cell cycle. The COOH-terminal 63 amino acids of Myt1 were identified as a Cdc2-cyclin B1 interaction domain. Myt1 mutants lacking this domain no longer bound cyclin B1 and did not efficiently phosphorylate Cdc2-cyclin B1 complexes in vitro. In addition, cells overproducing mutant forms of Myt1 lacking the interaction domain exhibited normal trafficking of cyclin B1 and unperturbed cell cycle progression. These results suggest that the docking of Cdc2-cyclin B1 complexes to the COOH terminus of Myt1 facilitates the phosphorylation of Cdc2 by Myt1 and that overproduction of Myt1 perturbs cell cycle progression by sequestering Cdc2-cyclin B1 complexes in the cytoplasm.\n"
],
"offsets": [
[
0,
1327
]
]
}
] | [
{
"id": "PMID-10373560_T1",
"type": "Gene_or_gene_product",
"offsets": [
[
24,
28
]
],
"text": [
"Myt1"
],
"normalized": []
},
{
"id": "PMID-10373560_T2",
"type": "Cellular_component",
"offsets": [
[
90,
103
]
],
"text": [
"intracellular"
],
"normalized": []
},
{
"id": "PMID-10373560_T3",
"type": "Complex",
"offsets": [
[
119,
133
]
],
"text": [
"Cdc2-cyclin B1"
],
"normalized": []
},
{
"id": "PMID-10373560_T4",
"type": "Gene_or_gene_product",
"offsets": [
[
150,
154
]
],
"text": [
"Myt1"
],
"normalized": []
},
{
"id": "PMID-10373560_T5",
"type": "Complex",
"offsets": [
[
203,
216
]
],
"text": [
"Cdc2-cyclin B"
],
"normalized": []
},
{
"id": "PMID-10373560_T6",
"type": "Gene_or_gene_product",
"offsets": [
[
246,
250
]
],
"text": [
"Cdc2"
],
"normalized": []
},
{
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662
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809
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}
] | [] | [] |
7 | PMID-10383454 | [
{
"id": "PMID-10383454__text",
"type": "abstract",
"text": [
"IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family. \nThe interleukin-1 receptor-associated kinase (IRAK) was first described as a signal transducer for interleukin-1 (IL-1) and has later been implicated in signal transduction of other members of the Toll/IL-1 receptor family. We now report the identification and characterization of a novel IRAK-like molecule. In contrast to the ubiquitously expressed IRAK and IRAK-2, this new IRAK-like molecule is found mainly in cells of monomyeloic origin and is, therefore, designated IRAK-M. Although IRAK-M and IRAK-2 exhibit only a negligible autophosphorylation activity, they can reconstitute the IL-1 response in a 293 mutant cell line lacking IRAK. In addition, we show for the first time that members of the IRAK family are indispensable elements of lipopolysaccharide signal transduction. The discovery of IRAK-M adds another level of complexity to our understanding of signaling by members of the Toll/IL-1 receptor family.\n"
],
"offsets": [
[
0,
1017
]
]
}
] | [
{
"id": "PMID-10383454_T1",
"type": "Gene_or_gene_product",
"offsets": [
[
0,
6
]
],
"text": [
"IRAK-M"
],
"normalized": []
},
{
"id": "PMID-10383454_T2",
"type": "Gene_or_gene_product",
"offsets": [
[
32,
37
]
],
"text": [
"Pelle"
],
"normalized": []
},
{
"id": "PMID-10383454_T3",
"type": "Gene_or_gene_product",
"offsets": [
[
38,
78
]
],
"text": [
"interleukin-1 receptor-associated kinase"
],
"normalized": []
},
{
"id": "PMID-10383454_T4",
"type": "Gene_or_gene_product",
"offsets": [
[
80,
84
]
],
"text": [
"IRAK"
],
"normalized": []
},
{
"id": "PMID-10383454_T5",
"type": "Gene_or_gene_product",
"offsets": [
[
99,
139
]
],
"text": [
"interleukin-1 receptor-associated kinase"
],
"normalized": []
},
{
"id": "PMID-10383454_T6",
"type": "Gene_or_gene_product",
"offsets": [
[
141,
145
]
],
"text": [
"IRAK"
],
"normalized": []
},
{
"id": "PMID-10383454_T7",
"type": "Gene_or_gene_product",
"offsets": [
[
194,
207
]
],
"text": [
"interleukin-1"
],
"normalized": []
},
{
"id": "PMID-10383454_T8",
"type": "Gene_or_gene_product",
"offsets": [
[
209,
213
]
],
"text": [
"IL-1"
],
"normalized": []
},
{
"id": "PMID-10383454_T9",
"type": "Gene_or_gene_product",
"offsets": [
[
292,
310
]
],
"text": [
"Toll/IL-1 receptor"
],
"normalized": []
},
{
"id": "PMID-10383454_T10",
"type": "Gene_or_gene_product",
"offsets": [
[
384,
388
]
],
"text": [
"IRAK"
],
"normalized": []
},
{
"id": "PMID-10383454_T11",
"type": "Gene_or_gene_product",
"offsets": [
[
446,
450
]
],
"text": [
"IRAK"
],
"normalized": []
},
{
"id": "PMID-10383454_T12",
"type": "Gene_or_gene_product",
"offsets": [
[
455,
461
]
],
"text": [
"IRAK-2"
],
"normalized": []
},
{
"id": "PMID-10383454_T13",
"type": "Gene_or_gene_product",
"offsets": [
[
472,
476
]
],
"text": [
"IRAK"
],
"normalized": []
},
{
"id": "PMID-10383454_T14",
"type": "Gene_or_gene_product",
"offsets": [
[
568,
574
]
],
"text": [
"IRAK-M"
],
"normalized": []
},
{
"id": "PMID-10383454_T15",
"type": "Gene_or_gene_product",
"offsets": [
[
585,
591
]
],
"text": [
"IRAK-M"
],
"normalized": []
},
{
"id": "PMID-10383454_T16",
"type": "Gene_or_gene_product",
"offsets": [
[
596,
602
]
],
"text": [
"IRAK-2"
],
"normalized": []
},
{
"id": "PMID-10383454_T17",
"type": "Gene_or_gene_product",
"offsets": [
[
685,
689
]
],
"text": [
"IL-1"
],
"normalized": []
},
{
"id": "PMID-10383454_T18",
"type": "Gene_or_gene_product",
"offsets": [
[
733,
737
]
],
"text": [
"IRAK"
],
"normalized": []
},
{
"id": "PMID-10383454_T19",
"type": "Gene_or_gene_product",
"offsets": [
[
799,
803
]
],
"text": [
"IRAK"
],
"normalized": []
},
{
"id": "PMID-10383454_T20",
"type": "Simple_chemical",
"offsets": [
[
841,
859
]
],
"text": [
"lipopolysaccharide"
],
"normalized": []
},
{
"id": "PMID-10383454_T21",
"type": "Gene_or_gene_product",
"offsets": [
[
898,
904
]
],
"text": [
"IRAK-M"
],
"normalized": []
},
{
"id": "PMID-10383454_T22",
"type": "Gene_or_gene_product",
"offsets": [
[
990,
1008
]
],
"text": [
"Toll/IL-1 receptor"
],
"normalized": []
}
] | [
{
"id": "PMID-10383454_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"transducer"
],
"offsets": [
[
179,
189
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10383454_T7"
},
{
"role": "Cause",
"ref_id": "PMID-10383454_T5"
}
]
},
{
"id": "PMID-10383454_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"implicated"
],
"offsets": [
[
234,
244
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10383454_E3"
},
{
"role": "Cause",
"ref_id": "PMID-10383454_T5"
}
]
},
{
"id": "PMID-10383454_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"transduction"
],
"offsets": [
[
255,
267
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10383454_T9"
}
]
},
{
"id": "PMID-10383454_E4",
"type": "Ubiquitination",
"trigger": {
"text": [
"ubiquitously"
],
"offsets": [
[
423,
435
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10383454_T11"
}
]
},
{
"id": "PMID-10383454_E5",
"type": "Ubiquitination",
"trigger": {
"text": [
"ubiquitously"
],
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423,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10383454_T12"
}
]
},
{
"id": "PMID-10383454_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
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[
436,
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]
]
},
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{
"role": "Theme",
"ref_id": "PMID-10383454_T11"
}
]
},
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"id": "PMID-10383454_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
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[
436,
445
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10383454_T12"
}
]
}
] | [
{
"id": "PMID-10383454_1",
"entity_ids": [
"PMID-10383454_T3",
"PMID-10383454_T4",
"PMID-10383454_T2"
]
},
{
"id": "PMID-10383454_2",
"entity_ids": [
"PMID-10383454_T5",
"PMID-10383454_T6"
]
},
{
"id": "PMID-10383454_3",
"entity_ids": [
"PMID-10383454_T7",
"PMID-10383454_T8"
]
}
] | [] |
8 | PMID-10385526 | [
{
"id": "PMID-10385526__text",
"type": "abstract",
"text": [
"The zinc finger protein A20 inhibits TNF-induced NF-kappaB-dependent gene expression by interfering with an RIP- or TRAF2-mediated transactivation signal and directly binds to a novel NF-kappaB-inhibiting protein ABIN. \nThe zinc finger protein A20 is a tumor necrosis factor (TNF)- and interleukin 1 (IL-1)-inducible protein that negatively regulates nuclear factor-kappa B (NF-kappaB)-dependent gene expression. However, the molecular mechanism by which A20 exerts this effect is still unclear. We show that A20 does not inhibit TNF- induced nuclear translocation and DNA binding of NF-kappaB, although it completely prevents the TNF- induced activation of an NF-kappaB-dependent reporter gene, as well as TNF-induced IL-6 and granulocyte macrophage-colony stimulating factor gene expression. Moreover, NF-kappaB activation induced by overexpression of the TNF receptor-associated proteins TNF receptor-associated death domain protein (TRADD), receptor interacting protein (RIP), and TNF recep- tor-associated factor 2 (TRAF2) was also inhibited by expression of A20, whereas NF-kappaB activation induced by overexpression of NF-kappaB-inducing kinase (NIK) or the human T cell leukemia virus type 1 (HTLV-1) Tax was unaffected. These results demonstrate that A20 inhibits NF-kappaB-dependent gene expression by interfering with a novel TNF-induced and RIP- or TRAF2-mediated pathway that is different from the NIK-IkappaB kinase pathway and that is specifically involved in the transactivation of NF-kappaB. Via yeast two-hybrid screening, we found that A20 binds to a novel protein, ABIN, which mimics the NF-kappaB inhibiting effects of A20 upon overexpression, suggesting that the effect of A20 is mediated by its interaction with this NF-kappaB inhibiting protein, ABIN.\n"
],
"offsets": [
[
0,
1777
]
]
}
] | [
{
"id": "PMID-10385526_T1",
"type": "Simple_chemical",
"offsets": [
[
4,
8
]
],
"text": [
"zinc"
],
"normalized": []
},
{
"id": "PMID-10385526_T2",
"type": "Gene_or_gene_product",
"offsets": [
[
24,
27
]
],
"text": [
"A20"
],
"normalized": []
},
{
"id": "PMID-10385526_T3",
"type": "Gene_or_gene_product",
"offsets": [
[
37,
40
]
],
"text": [
"TNF"
],
"normalized": []
},
{
"id": "PMID-10385526_T4",
"type": "Complex",
"offsets": [
[
49,
58
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10385526_T5",
"type": "Gene_or_gene_product",
"offsets": [
[
108,
111
]
],
"text": [
"RIP"
],
"normalized": []
},
{
"id": "PMID-10385526_T6",
"type": "Gene_or_gene_product",
"offsets": [
[
116,
121
]
],
"text": [
"TRAF2"
],
"normalized": []
},
{
"id": "PMID-10385526_T7",
"type": "Complex",
"offsets": [
[
184,
193
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10385526_T8",
"type": "Gene_or_gene_product",
"offsets": [
[
213,
217
]
],
"text": [
"ABIN"
],
"normalized": []
},
{
"id": "PMID-10385526_T9",
"type": "Simple_chemical",
"offsets": [
[
224,
228
]
],
"text": [
"zinc"
],
"normalized": []
},
{
"id": "PMID-10385526_T10",
"type": "Gene_or_gene_product",
"offsets": [
[
244,
247
]
],
"text": [
"A20"
],
"normalized": []
},
{
"id": "PMID-10385526_T11",
"type": "Gene_or_gene_product",
"offsets": [
[
253,
274
]
],
"text": [
"tumor necrosis factor"
],
"normalized": []
},
{
"id": "PMID-10385526_T12",
"type": "Gene_or_gene_product",
"offsets": [
[
276,
279
]
],
"text": [
"TNF"
],
"normalized": []
},
{
"id": "PMID-10385526_T13",
"type": "Gene_or_gene_product",
"offsets": [
[
286,
299
]
],
"text": [
"interleukin 1"
],
"normalized": []
},
{
"id": "PMID-10385526_T14",
"type": "Gene_or_gene_product",
"offsets": [
[
301,
305
]
],
"text": [
"IL-1"
],
"normalized": []
},
{
"id": "PMID-10385526_T15",
"type": "Complex",
"offsets": [
[
351,
373
]
],
"text": [
"nuclear factor-kappa B"
],
"normalized": []
},
{
"id": "PMID-10385526_T16",
"type": "Complex",
"offsets": [
[
375,
384
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10385526_T17",
"type": "Gene_or_gene_product",
"offsets": [
[
455,
458
]
],
"text": [
"A20"
],
"normalized": []
},
{
"id": "PMID-10385526_T18",
"type": "Gene_or_gene_product",
"offsets": [
[
509,
512
]
],
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"A20"
],
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},
{
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"type": "Gene_or_gene_product",
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[
530,
533
]
],
"text": [
"TNF"
],
"normalized": []
},
{
"id": "PMID-10385526_T20",
"type": "Cellular_component",
"offsets": [
[
543,
550
]
],
"text": [
"nuclear"
],
"normalized": []
},
{
"id": "PMID-10385526_T21",
"type": "Complex",
"offsets": [
[
584,
593
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10385526_T22",
"type": "Gene_or_gene_product",
"offsets": [
[
631,
634
]
],
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"TNF"
],
"normalized": []
},
{
"id": "PMID-10385526_T23",
"type": "Complex",
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[
661,
670
]
],
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"NF-kappaB"
],
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},
{
"id": "PMID-10385526_T24",
"type": "Gene_or_gene_product",
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[
707,
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]
],
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"TNF"
],
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},
{
"id": "PMID-10385526_T25",
"type": "Gene_or_gene_product",
"offsets": [
[
719,
723
]
],
"text": [
"IL-6"
],
"normalized": []
},
{
"id": "PMID-10385526_T26",
"type": "Gene_or_gene_product",
"offsets": [
[
728,
776
]
],
"text": [
"granulocyte macrophage-colony stimulating factor"
],
"normalized": []
},
{
"id": "PMID-10385526_T27",
"type": "Complex",
"offsets": [
[
804,
813
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10385526_T28",
"type": "Gene_or_gene_product",
"offsets": [
[
858,
870
]
],
"text": [
"TNF receptor"
],
"normalized": []
},
{
"id": "PMID-10385526_T29",
"type": "Gene_or_gene_product",
"offsets": [
[
891,
935
]
],
"text": [
"TNF receptor-associated death domain protein"
],
"normalized": []
},
{
"id": "PMID-10385526_T30",
"type": "Gene_or_gene_product",
"offsets": [
[
937,
942
]
],
"text": [
"TRADD"
],
"normalized": []
},
{
"id": "PMID-10385526_T31",
"type": "Gene_or_gene_product",
"offsets": [
[
945,
973
]
],
"text": [
"receptor interacting protein"
],
"normalized": []
},
{
"id": "PMID-10385526_T32",
"type": "Gene_or_gene_product",
"offsets": [
[
975,
978
]
],
"text": [
"RIP"
],
"normalized": []
},
{
"id": "PMID-10385526_T33",
"type": "Gene_or_gene_product",
"offsets": [
[
985,
1019
]
],
"text": [
"TNF recep- tor-associated factor 2"
],
"normalized": []
},
{
"id": "PMID-10385526_T34",
"type": "Gene_or_gene_product",
"offsets": [
[
1021,
1026
]
],
"text": [
"TRAF2"
],
"normalized": []
},
{
"id": "PMID-10385526_T35",
"type": "Gene_or_gene_product",
"offsets": [
[
1064,
1067
]
],
"text": [
"A20"
],
"normalized": []
},
{
"id": "PMID-10385526_T36",
"type": "Complex",
"offsets": [
[
1077,
1086
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10385526_T37",
"type": "Gene_or_gene_product",
"offsets": [
[
1127,
1152
]
],
"text": [
"NF-kappaB-inducing kinase"
],
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},
{
"id": "PMID-10385526_T38",
"type": "Gene_or_gene_product",
"offsets": [
[
1154,
1157
]
],
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"NIK"
],
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},
{
"id": "PMID-10385526_T39",
"type": "Gene_or_gene_product",
"offsets": [
[
1210,
1213
]
],
"text": [
"Tax"
],
"normalized": []
},
{
"id": "PMID-10385526_T40",
"type": "Gene_or_gene_product",
"offsets": [
[
1261,
1264
]
],
"text": [
"A20"
],
"normalized": []
},
{
"id": "PMID-10385526_T41",
"type": "Complex",
"offsets": [
[
1274,
1283
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10385526_T42",
"type": "Gene_or_gene_product",
"offsets": [
[
1338,
1341
]
],
"text": [
"TNF"
],
"normalized": []
},
{
"id": "PMID-10385526_T43",
"type": "Gene_or_gene_product",
"offsets": [
[
1354,
1357
]
],
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"RIP"
],
"normalized": []
},
{
"id": "PMID-10385526_T44",
"type": "Gene_or_gene_product",
"offsets": [
[
1362,
1367
]
],
"text": [
"TRAF2"
],
"normalized": []
},
{
"id": "PMID-10385526_T45",
"type": "Gene_or_gene_product",
"offsets": [
[
1412,
1415
]
],
"text": [
"NIK"
],
"normalized": []
},
{
"id": "PMID-10385526_T46",
"type": "Complex",
"offsets": [
[
1416,
1430
]
],
"text": [
"IkappaB kinase"
],
"normalized": []
},
{
"id": "PMID-10385526_T47",
"type": "Complex",
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[
1499,
1508
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10385526_T48",
"type": "Gene_or_gene_product",
"offsets": [
[
1556,
1559
]
],
"text": [
"A20"
],
"normalized": []
},
{
"id": "PMID-10385526_T49",
"type": "Gene_or_gene_product",
"offsets": [
[
1586,
1590
]
],
"text": [
"ABIN"
],
"normalized": []
},
{
"id": "PMID-10385526_T50",
"type": "Complex",
"offsets": [
[
1609,
1618
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10385526_T51",
"type": "Gene_or_gene_product",
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[
1641,
1644
]
],
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"A20"
],
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},
{
"id": "PMID-10385526_T52",
"type": "Gene_or_gene_product",
"offsets": [
[
1696,
1699
]
],
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"A20"
],
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},
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"type": "Complex",
"offsets": [
[
1741,
1750
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10385526_T54",
"type": "Gene_or_gene_product",
"offsets": [
[
1771,
1775
]
],
"text": [
"ABIN"
],
"normalized": []
}
] | [
{
"id": "PMID-10385526_E1",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
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[
167,
172
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10385526_T8"
},
{
"role": "Theme",
"ref_id": "PMID-10385526_T2"
}
]
},
{
"id": "PMID-10385526_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibiting"
],
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194,
204
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10385526_T7"
},
{
"role": "Cause",
"ref_id": "PMID-10385526_T8"
}
]
},
{
"id": "PMID-10385526_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"inducible"
],
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307,
316
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] | [] |
9 | PMID-10389141 | [
{
"id": "PMID-10389141__text",
"type": "abstract",
"text": [
"Role of MAO A and B in neurotransmitter metabolism and behavior. \nMAO (monoamine oxidase) A and B are key isoenzymes that degrade biogenic and dietary amines. MAO A preferentially oxidizes serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE), whereas MAO B preferentially oxidizes phenylethylamine (PEA). Both forms can oxidize dopamine (DA). However, the substrate specificity overlap and the in vivo function of these two isoenzymes is not clear. Recently, we have shown that MAO A and B knock-out (KO) mice exhibit distinct differences in neurotransmitter metabolism and behavior. MAO A KO mice have elevated brain levels of 5-HT, NE and DA and manifest aggressive behavior similar to men with a deletion of MAO A. In contrast, MAO B KO mice do not exhibit aggression and only levels of PEA are increased. Both MAO A and B KO mice show increased reactivity to stress. Taken together, these results suggest that MAO A and B have distinctly different roles in monoamine metabolism. Further, these mice are valuable models for investigating the role of monoamines in psychoses and neurodegenerative and stress-related disorders.\n"
],
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] | [
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},
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{
"id": "PMID-10389141_T26",
"type": "Gene_or_gene_product",
"offsets": [
[
823,
828
]
],
"text": [
"MAO A"
],
"normalized": []
},
{
"id": "PMID-10389141_T27",
"type": "Gene_or_gene_product",
"offsets": [
[
833,
834
]
],
"text": [
"B"
],
"normalized": []
},
{
"id": "PMID-10389141_T28",
"type": "Gene_or_gene_product",
"offsets": [
[
923,
928
]
],
"text": [
"MAO A"
],
"normalized": []
},
{
"id": "PMID-10389141_T29",
"type": "Gene_or_gene_product",
"offsets": [
[
933,
934
]
],
"text": [
"B"
],
"normalized": []
},
{
"id": "PMID-10389141_T30",
"type": "Simple_chemical",
"offsets": [
[
970,
979
]
],
"text": [
"monoamine"
],
"normalized": []
}
] | [
{
"id": "PMID-10389141_E1",
"type": "Conversion",
"trigger": {
"text": [
"oxidizes"
],
"offsets": [
[
180,
188
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10389141_T7"
}
]
},
{
"id": "PMID-10389141_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"oxidizes"
],
"offsets": [
[
180,
188
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10389141_T6"
},
{
"role": "Theme",
"ref_id": "PMID-10389141_E1"
}
]
},
{
"id": "PMID-10389141_E3",
"type": "Conversion",
"trigger": {
"text": [
"oxidizes"
],
"offsets": [
[
180,
188
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10389141_T10"
}
]
},
{
"id": "PMID-10389141_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"oxidizes"
],
"offsets": [
[
180,
188
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10389141_T6"
},
{
"role": "Theme",
"ref_id": "PMID-10389141_E3"
}
]
},
{
"id": "PMID-10389141_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"oxidizes"
],
"offsets": [
[
281,
289
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10389141_T12"
},
{
"role": "Theme",
"ref_id": "PMID-10389141_E6"
}
]
},
{
"id": "PMID-10389141_E6",
"type": "Conversion",
"trigger": {
"text": [
"oxidizes"
],
"offsets": [
[
281,
289
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10389141_T13"
}
]
},
{
"id": "PMID-10389141_E7",
"type": "Conversion",
"trigger": {
"text": [
"oxidize"
],
"offsets": [
[
329,
336
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10389141_T15"
}
]
},
{
"id": "PMID-10389141_E8",
"type": "Inactivation",
"trigger": {
"text": [
"knock-out"
],
"offsets": [
[
499,
508
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10389141_T17"
}
]
},
{
"id": "PMID-10389141_E9",
"type": "Inactivation",
"trigger": {
"text": [
"knock-out"
],
"offsets": [
[
499,
508
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10389141_T18"
}
]
},
{
"id": "PMID-10389141_E10",
"type": "Inactivation",
"trigger": {
"text": [
"KO"
],
"offsets": [
[
599,
601
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10389141_T19"
}
]
},
{
"id": "PMID-10389141_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"elevated"
],
"offsets": [
[
612,
620
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10389141_E10"
},
{
"role": "Theme",
"ref_id": "PMID-10389141_T20"
}
]
},
{
"id": "PMID-10389141_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"elevated"
],
"offsets": [
[
612,
620
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10389141_E10"
},
{
"role": "Theme",
"ref_id": "PMID-10389141_T21"
}
]
},
{
"id": "PMID-10389141_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"elevated"
],
"offsets": [
[
612,
620
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10389141_E10"
},
{
"role": "Theme",
"ref_id": "PMID-10389141_T22"
}
]
},
{
"id": "PMID-10389141_E14",
"type": "Inactivation",
"trigger": {
"text": [
"deletion"
],
"offsets": [
[
708,
716
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10389141_T23"
}
]
},
{
"id": "PMID-10389141_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
807,
816
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10389141_T25"
}
]
}
] | [
{
"id": "PMID-10389141_1",
"entity_ids": [
"PMID-10389141_T7",
"PMID-10389141_T8",
"PMID-10389141_T9"
]
},
{
"id": "PMID-10389141_2",
"entity_ids": [
"PMID-10389141_T10",
"PMID-10389141_T11"
]
},
{
"id": "PMID-10389141_3",
"entity_ids": [
"PMID-10389141_T13",
"PMID-10389141_T14"
]
},
{
"id": "PMID-10389141_4",
"entity_ids": [
"PMID-10389141_T15",
"PMID-10389141_T16"
]
}
] | [] |
10 | PMID-10391247 | [
{
"id": "PMID-10391247__text",
"type": "abstract",
"text": [
"The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF. \nThe Wnt signalling pathway regulates many developmental processes through a complex of beta-catenin and the T-cell factor/lymphoid enhancer factor (TCF/LEF) family of high-mobility-group transcription factors. Wnt stabilizes cytosolic beta-catenin, which then binds to TCF and activates gene transcription. This signalling cascade is conserved in vertebrates, Drosophila and Caenorhabditis elegans. In C. elegans, the proteins MOM-4 and LIT-1 regulate Wnt signalling to polarize responding cells during embryogenesis. MOM-4 and LIT-1 are homologous to TAK1 (a kinase activated by transforming growth factor-beta) mitogen-activated protein-kinase-kinase kinase (MAP3K) and MAP kinase (MAPK)-related NEMO-like kinase (NLK), respectively, in mammalian cells. These results raise the possibility that TAK1 and NLK are also involved in Wnt signalling in mammalian cells. Here we show that TAK1 activation stimulates NLK activity and downregulates transcriptional activation mediated by beta-catenin and TCF. Injection of NLK suppresses the induction of axis duplication by microinjected beta-catenin in Xenopus embryos. NLK phosphorylates TCF/LEF factors and inhibits the interaction of the beta-catenin-TCF complex with DNA. Thus, the TAK1-NLK-MAPK-like pathway negatively regulates the Wnt signalling pathway.\n"
],
"offsets": [
[
0,
1416
]
]
}
] | [
{
"id": "PMID-10391247_T1",
"type": "Gene_or_gene_product",
"offsets": [
[
4,
8
]
],
"text": [
"TAK1"
],
"normalized": []
},
{
"id": "PMID-10391247_T2",
"type": "Gene_or_gene_product",
"offsets": [
[
9,
12
]
],
"text": [
"NLK"
],
"normalized": []
},
{
"id": "PMID-10391247_T3",
"type": "Gene_or_gene_product",
"offsets": [
[
13,
17
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10391247_T4",
"type": "Gene_or_gene_product",
"offsets": [
[
65,
77
]
],
"text": [
"beta-catenin"
],
"normalized": []
},
{
"id": "PMID-10391247_T5",
"type": "Gene_or_gene_product",
"offsets": [
[
103,
106
]
],
"text": [
"TCF"
],
"normalized": []
},
{
"id": "PMID-10391247_T6",
"type": "Gene_or_gene_product",
"offsets": [
[
113,
116
]
],
"text": [
"Wnt"
],
"normalized": []
},
{
"id": "PMID-10391247_T7",
"type": "Gene_or_gene_product",
"offsets": [
[
196,
208
]
],
"text": [
"beta-catenin"
],
"normalized": []
},
{
"id": "PMID-10391247_T8",
"type": "Gene_or_gene_product",
"offsets": [
[
217,
230
]
],
"text": [
"T-cell factor"
],
"normalized": []
},
{
"id": "PMID-10391247_T9",
"type": "Gene_or_gene_product",
"offsets": [
[
231,
255
]
],
"text": [
"lymphoid enhancer factor"
],
"normalized": []
},
{
"id": "PMID-10391247_T10",
"type": "Gene_or_gene_product",
"offsets": [
[
257,
260
]
],
"text": [
"TCF"
],
"normalized": []
},
{
"id": "PMID-10391247_T11",
"type": "Gene_or_gene_product",
"offsets": [
[
261,
264
]
],
"text": [
"LEF"
],
"normalized": []
},
{
"id": "PMID-10391247_T12",
"type": "Gene_or_gene_product",
"offsets": [
[
319,
322
]
],
"text": [
"Wnt"
],
"normalized": []
},
{
"id": "PMID-10391247_T13",
"type": "Cellular_component",
"offsets": [
[
334,
343
]
],
"text": [
"cytosolic"
],
"normalized": []
},
{
"id": "PMID-10391247_T14",
"type": "Gene_or_gene_product",
"offsets": [
[
344,
356
]
],
"text": [
"beta-catenin"
],
"normalized": []
},
{
"id": "PMID-10391247_T15",
"type": "Gene_or_gene_product",
"offsets": [
[
378,
381
]
],
"text": [
"TCF"
],
"normalized": []
},
{
"id": "PMID-10391247_T16",
"type": "Gene_or_gene_product",
"offsets": [
[
536,
541
]
],
"text": [
"MOM-4"
],
"normalized": []
},
{
"id": "PMID-10391247_T17",
"type": "Gene_or_gene_product",
"offsets": [
[
546,
551
]
],
"text": [
"LIT-1"
],
"normalized": []
},
{
"id": "PMID-10391247_T18",
"type": "Gene_or_gene_product",
"offsets": [
[
561,
564
]
],
"text": [
"Wnt"
],
"normalized": []
},
{
"id": "PMID-10391247_T19",
"type": "Gene_or_gene_product",
"offsets": [
[
627,
632
]
],
"text": [
"MOM-4"
],
"normalized": []
},
{
"id": "PMID-10391247_T20",
"type": "Gene_or_gene_product",
"offsets": [
[
637,
642
]
],
"text": [
"LIT-1"
],
"normalized": []
},
{
"id": "PMID-10391247_T21",
"type": "Gene_or_gene_product",
"offsets": [
[
661,
665
]
],
"text": [
"TAK1"
],
"normalized": []
},
{
"id": "PMID-10391247_T22",
"type": "Gene_or_gene_product",
"offsets": [
[
689,
720
]
],
"text": [
"transforming growth factor-beta"
],
"normalized": []
},
{
"id": "PMID-10391247_T23",
"type": "Gene_or_gene_product",
"offsets": [
[
722,
768
]
],
"text": [
"mitogen-activated protein-kinase-kinase kinase"
],
"normalized": []
},
{
"id": "PMID-10391247_T24",
"type": "Gene_or_gene_product",
"offsets": [
[
770,
775
]
],
"text": [
"MAP3K"
],
"normalized": []
},
{
"id": "PMID-10391247_T25",
"type": "Gene_or_gene_product",
"offsets": [
[
781,
791
]
],
"text": [
"MAP kinase"
],
"normalized": []
},
{
"id": "PMID-10391247_T26",
"type": "Gene_or_gene_product",
"offsets": [
[
793,
797
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10391247_T27",
"type": "Gene_or_gene_product",
"offsets": [
[
807,
823
]
],
"text": [
"NEMO-like kinase"
],
"normalized": []
},
{
"id": "PMID-10391247_T28",
"type": "Gene_or_gene_product",
"offsets": [
[
825,
828
]
],
"text": [
"NLK"
],
"normalized": []
},
{
"id": "PMID-10391247_T29",
"type": "Gene_or_gene_product",
"offsets": [
[
906,
910
]
],
"text": [
"TAK1"
],
"normalized": []
},
{
"id": "PMID-10391247_T30",
"type": "Gene_or_gene_product",
"offsets": [
[
915,
918
]
],
"text": [
"NLK"
],
"normalized": []
},
{
"id": "PMID-10391247_T31",
"type": "Gene_or_gene_product",
"offsets": [
[
940,
943
]
],
"text": [
"Wnt"
],
"normalized": []
},
{
"id": "PMID-10391247_T32",
"type": "Gene_or_gene_product",
"offsets": [
[
993,
997
]
],
"text": [
"TAK1"
],
"normalized": []
},
{
"id": "PMID-10391247_T33",
"type": "Gene_or_gene_product",
"offsets": [
[
1020,
1023
]
],
"text": [
"NLK"
],
"normalized": []
},
{
"id": "PMID-10391247_T34",
"type": "Gene_or_gene_product",
"offsets": [
[
1090,
1102
]
],
"text": [
"beta-catenin"
],
"normalized": []
},
{
"id": "PMID-10391247_T35",
"type": "Gene_or_gene_product",
"offsets": [
[
1107,
1110
]
],
"text": [
"TCF"
],
"normalized": []
},
{
"id": "PMID-10391247_T36",
"type": "Gene_or_gene_product",
"offsets": [
[
1125,
1128
]
],
"text": [
"NLK"
],
"normalized": []
},
{
"id": "PMID-10391247_T37",
"type": "Gene_or_gene_product",
"offsets": [
[
1191,
1203
]
],
"text": [
"beta-catenin"
],
"normalized": []
},
{
"id": "PMID-10391247_T38",
"type": "Gene_or_gene_product",
"offsets": [
[
1224,
1227
]
],
"text": [
"NLK"
],
"normalized": []
},
{
"id": "PMID-10391247_T39",
"type": "Gene_or_gene_product",
"offsets": [
[
1243,
1246
]
],
"text": [
"TCF"
],
"normalized": []
},
{
"id": "PMID-10391247_T40",
"type": "Gene_or_gene_product",
"offsets": [
[
1247,
1258
]
],
"text": [
"LEF factors"
],
"normalized": []
},
{
"id": "PMID-10391247_T41",
"type": "Complex",
"offsets": [
[
1295,
1311
]
],
"text": [
"beta-catenin-TCF"
],
"normalized": []
},
{
"id": "PMID-10391247_T42",
"type": "Gene_or_gene_product",
"offsets": [
[
1340,
1344
]
],
"text": [
"TAK1"
],
"normalized": []
},
{
"id": "PMID-10391247_T43",
"type": "Gene_or_gene_product",
"offsets": [
[
1345,
1348
]
],
"text": [
"NLK"
],
"normalized": []
},
{
"id": "PMID-10391247_T44",
"type": "Gene_or_gene_product",
"offsets": [
[
1349,
1353
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10391247_T45",
"type": "Gene_or_gene_product",
"offsets": [
[
1392,
1395
]
],
"text": [
"Wnt"
],
"normalized": []
}
] | [
{
"id": "PMID-10391247_E1",
"type": "Pathway",
"trigger": {
"text": [
"pathway"
],
"offsets": [
[
26,
33
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-10391247_T1"
},
{
"role": "Participant",
"ref_id": "PMID-10391247_T2"
},
{
"role": "Participant",
"ref_id": "PMID-10391247_T3"
}
]
},
{
"id": "PMID-10391247_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"antagonizes"
],
"offsets": [
[
34,
45
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10391247_E1"
},
{
"role": "Theme",
"ref_id": "PMID-10391247_E3"
}
]
},
{
"id": "PMID-10391247_E3",
"type": "Pathway",
"trigger": {
"text": [
"signalling"
],
"offsets": [
[
46,
56
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-10391247_T4"
},
{
"role": "Participant",
"ref_id": "PMID-10391247_T5"
}
]
},
{
"id": "PMID-10391247_E4",
"type": "Pathway",
"trigger": {
"text": [
"signalling pathway"
],
"offsets": [
[
117,
135
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-10391247_T6"
}
]
},
{
"id": "PMID-10391247_E5",
"type": "Regulation",
"trigger": {
"text": [
"stabilizes"
],
"offsets": [
[
323,
333
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10391247_T12"
},
{
"role": "Theme",
"ref_id": "PMID-10391247_T14"
}
]
},
{
"id": "PMID-10391247_E6",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
369,
374
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10391247_T14"
},
{
"role": "Theme",
"ref_id": "PMID-10391247_T15"
}
]
},
{
"id": "PMID-10391247_E7",
"type": "Regulation",
"trigger": {
"text": [
"regulate"
],
"offsets": [
[
552,
560
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10391247_E9"
},
{
"role": "Cause",
"ref_id": "PMID-10391247_T17"
}
]
},
{
"id": "PMID-10391247_E8",
"type": "Regulation",
"trigger": {
"text": [
"regulate"
],
"offsets": [
[
552,
560
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10391247_E9"
},
{
"role": "Cause",
"ref_id": "PMID-10391247_T16"
}
]
},
{
"id": "PMID-10391247_E9",
"type": "Pathway",
"trigger": {
"text": [
"signalling"
],
"offsets": [
[
565,
575
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-10391247_T18"
}
]
},
{
"id": "PMID-10391247_E10",
"type": "Activation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
676,
685
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10391247_T22"
},
{
"role": "Theme",
"ref_id": "PMID-10391247_T21"
}
]
},
{
"id": "PMID-10391247_E11",
"type": "Regulation",
"trigger": {
"text": [
"involved"
],
"offsets": [
[
928,
936
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10391247_E13"
},
{
"role": "Cause",
"ref_id": "PMID-10391247_T29"
}
]
},
{
"id": "PMID-10391247_E12",
"type": "Regulation",
"trigger": {
"text": [
"involved"
],
"offsets": [
[
928,
936
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10391247_E13"
},
{
"role": "Cause",
"ref_id": "PMID-10391247_T30"
}
]
},
{
"id": "PMID-10391247_E13",
"type": "Pathway",
"trigger": {
"text": [
"signalling"
],
"offsets": [
[
944,
954
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-10391247_T31"
}
]
},
{
"id": "PMID-10391247_E14",
"type": "Activation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
998,
1008
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10391247_T32"
}
]
},
{
"id": "PMID-10391247_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulates"
],
"offsets": [
[
1009,
1019
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10391247_E14"
},
{
"role": "Theme",
"ref_id": "PMID-10391247_T33"
}
]
},
{
"id": "PMID-10391247_E16",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylates"
],
"offsets": [
[
1228,
1242
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10391247_T38"
},
{
"role": "Theme",
"ref_id": "PMID-10391247_T39"
}
]
},
{
"id": "PMID-10391247_E17",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylates"
],
"offsets": [
[
1228,
1242
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10391247_T38"
},
{
"role": "Theme",
"ref_id": "PMID-10391247_T40"
}
]
},
{
"id": "PMID-10391247_E18",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
1263,
1271
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10391247_E19"
},
{
"role": "Cause",
"ref_id": "PMID-10391247_T38"
}
]
},
{
"id": "PMID-10391247_E19",
"type": "Binding",
"trigger": {
"text": [
"interaction"
],
"offsets": [
[
1276,
1287
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10391247_T41"
}
]
},
{
"id": "PMID-10391247_E20",
"type": "Pathway",
"trigger": {
"text": [
"pathway"
],
"offsets": [
[
1359,
1366
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-10391247_T42"
},
{
"role": "Participant",
"ref_id": "PMID-10391247_T43"
},
{
"role": "Participant",
"ref_id": "PMID-10391247_T44"
}
]
},
{
"id": "PMID-10391247_E21",
"type": "Negative_regulation",
"trigger": {
"text": [
"negatively regulates"
],
"offsets": [
[
1367,
1387
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10391247_E20"
},
{
"role": "Theme",
"ref_id": "PMID-10391247_E22"
}
]
},
{
"id": "PMID-10391247_E22",
"type": "Pathway",
"trigger": {
"text": [
"signalling pathway"
],
"offsets": [
[
1396,
1414
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-10391247_T45"
}
]
}
] | [
{
"id": "PMID-10391247_1",
"entity_ids": [
"PMID-10391247_T8",
"PMID-10391247_T10"
]
},
{
"id": "PMID-10391247_2",
"entity_ids": [
"PMID-10391247_T9",
"PMID-10391247_T11"
]
}
] | [] |
11 | PMID-10421629 | [
{
"id": "PMID-10421629__text",
"type": "abstract",
"text": [
"Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex. \nThe stabilization of beta-catenin is a key regulatory step during cell fate changes and transformations to tumor cells. Several interacting proteins, including Axin, APC, and the protein kinase GSK-3beta are implicated in regulating beta-catenin phosphorylation and its subsequent degradation. Wnt signaling stabilizes beta-catenin, but it was not clear whether and how Wnt signaling regulates the beta-catenin complex. Here we show that Axin is dephosphorylated in response to Wnt signaling. The dephosphorylated Axin binds beta-catenin less efficiently than the phosphorylated form. Thus, Wnt signaling lowers Axin's affinity for beta-catenin, thereby disengaging beta-catenin from the degradation machinery. \n"
],
"offsets": [
[
0,
796
]
]
}
] | [
{
"id": "PMID-10421629_T1",
"type": "Gene_or_gene_product",
"offsets": [
[
0,
3
]
],
"text": [
"Wnt"
],
"normalized": []
},
{
"id": "PMID-10421629_T2",
"type": "Gene_or_gene_product",
"offsets": [
[
33,
37
]
],
"text": [
"axin"
],
"normalized": []
},
{
"id": "PMID-10421629_T3",
"type": "Gene_or_gene_product",
"offsets": [
[
47,
59
]
],
"text": [
"beta-catenin"
],
"normalized": []
},
{
"id": "PMID-10421629_T4",
"type": "Complex",
"offsets": [
[
69,
81
]
],
"text": [
"axin complex"
],
"normalized": []
},
{
"id": "PMID-10421629_T5",
"type": "Gene_or_gene_product",
"offsets": [
[
105,
117
]
],
"text": [
"beta-catenin"
],
"normalized": []
},
{
"id": "PMID-10421629_T6",
"type": "Gene_or_gene_product",
"offsets": [
[
244,
248
]
],
"text": [
"Axin"
],
"normalized": []
},
{
"id": "PMID-10421629_T7",
"type": "Gene_or_gene_product",
"offsets": [
[
250,
253
]
],
"text": [
"APC"
],
"normalized": []
},
{
"id": "PMID-10421629_T8",
"type": "Gene_or_gene_product",
"offsets": [
[
278,
287
]
],
"text": [
"GSK-3beta"
],
"normalized": []
},
{
"id": "PMID-10421629_T9",
"type": "Gene_or_gene_product",
"offsets": [
[
317,
329
]
],
"text": [
"beta-catenin"
],
"normalized": []
},
{
"id": "PMID-10421629_T10",
"type": "Gene_or_gene_product",
"offsets": [
[
378,
381
]
],
"text": [
"Wnt"
],
"normalized": []
},
{
"id": "PMID-10421629_T11",
"type": "Gene_or_gene_product",
"offsets": [
[
403,
415
]
],
"text": [
"beta-catenin"
],
"normalized": []
},
{
"id": "PMID-10421629_T12",
"type": "Gene_or_gene_product",
"offsets": [
[
454,
457
]
],
"text": [
"Wnt"
],
"normalized": []
},
{
"id": "PMID-10421629_T13",
"type": "Complex",
"offsets": [
[
482,
502
]
],
"text": [
"beta-catenin complex"
],
"normalized": []
},
{
"id": "PMID-10421629_T14",
"type": "Gene_or_gene_product",
"offsets": [
[
522,
526
]
],
"text": [
"Axin"
],
"normalized": []
},
{
"id": "PMID-10421629_T15",
"type": "Gene_or_gene_product",
"offsets": [
[
562,
565
]
],
"text": [
"Wnt"
],
"normalized": []
},
{
"id": "PMID-10421629_T16",
"type": "Gene_or_gene_product",
"offsets": [
[
598,
602
]
],
"text": [
"Axin"
],
"normalized": []
},
{
"id": "PMID-10421629_T17",
"type": "Gene_or_gene_product",
"offsets": [
[
609,
621
]
],
"text": [
"beta-catenin"
],
"normalized": []
},
{
"id": "PMID-10421629_T18",
"type": "Gene_or_gene_product",
"offsets": [
[
675,
678
]
],
"text": [
"Wnt"
],
"normalized": []
},
{
"id": "PMID-10421629_T19",
"type": "Gene_or_gene_product",
"offsets": [
[
696,
700
]
],
"text": [
"Axin"
],
"normalized": []
},
{
"id": "PMID-10421629_T20",
"type": "Gene_or_gene_product",
"offsets": [
[
716,
728
]
],
"text": [
"beta-catenin"
],
"normalized": []
},
{
"id": "PMID-10421629_T21",
"type": "Gene_or_gene_product",
"offsets": [
[
750,
762
]
],
"text": [
"beta-catenin"
],
"normalized": []
}
] | [
{
"id": "PMID-10421629_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
4,
11
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10421629_T1"
},
{
"role": "Theme",
"ref_id": "PMID-10421629_E2"
}
]
},
{
"id": "PMID-10421629_E2",
"type": "Dephosphorylation",
"trigger": {
"text": [
"dephosphorylation"
],
"offsets": [
[
12,
29
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T2"
}
]
},
{
"id": "PMID-10421629_E3",
"type": "Dissociation",
"trigger": {
"text": [
"releases"
],
"offsets": [
[
38,
46
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T4"
},
{
"role": "Product",
"ref_id": "PMID-10421629_T3"
}
]
},
{
"id": "PMID-10421629_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"releases"
],
"offsets": [
[
38,
46
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10421629_E2"
},
{
"role": "Theme",
"ref_id": "PMID-10421629_E3"
}
]
},
{
"id": "PMID-10421629_E5",
"type": "Regulation",
"trigger": {
"text": [
"stabilization"
],
"offsets": [
[
88,
101
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T5"
}
]
},
{
"id": "PMID-10421629_E6",
"type": "Binding",
"trigger": {
"text": [
"interacting"
],
"offsets": [
[
212,
223
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T6"
}
]
},
{
"id": "PMID-10421629_E7",
"type": "Binding",
"trigger": {
"text": [
"interacting"
],
"offsets": [
[
212,
223
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T7"
}
]
},
{
"id": "PMID-10421629_E8",
"type": "Binding",
"trigger": {
"text": [
"interacting"
],
"offsets": [
[
212,
223
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T8"
}
]
},
{
"id": "PMID-10421629_E9",
"type": "Regulation",
"trigger": {
"text": [
"regulating"
],
"offsets": [
[
306,
316
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_E15"
},
{
"role": "Cause",
"ref_id": "PMID-10421629_T8"
}
]
},
{
"id": "PMID-10421629_E10",
"type": "Regulation",
"trigger": {
"text": [
"regulating"
],
"offsets": [
[
306,
316
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_E15"
},
{
"role": "Cause",
"ref_id": "PMID-10421629_T7"
}
]
},
{
"id": "PMID-10421629_E11",
"type": "Regulation",
"trigger": {
"text": [
"regulating"
],
"offsets": [
[
306,
316
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_E15"
},
{
"role": "Cause",
"ref_id": "PMID-10421629_T6"
}
]
},
{
"id": "PMID-10421629_E12",
"type": "Regulation",
"trigger": {
"text": [
"regulating"
],
"offsets": [
[
306,
316
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_E16"
},
{
"role": "Cause",
"ref_id": "PMID-10421629_T7"
}
]
},
{
"id": "PMID-10421629_E13",
"type": "Regulation",
"trigger": {
"text": [
"regulating"
],
"offsets": [
[
306,
316
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_E16"
},
{
"role": "Cause",
"ref_id": "PMID-10421629_T8"
}
]
},
{
"id": "PMID-10421629_E14",
"type": "Regulation",
"trigger": {
"text": [
"regulating"
],
"offsets": [
[
306,
316
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_E16"
},
{
"role": "Cause",
"ref_id": "PMID-10421629_T6"
}
]
},
{
"id": "PMID-10421629_E15",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
330,
345
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T9"
}
]
},
{
"id": "PMID-10421629_E16",
"type": "Degradation",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
365,
376
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T9"
}
]
},
{
"id": "PMID-10421629_E17",
"type": "Pathway",
"trigger": {
"text": [
"signaling"
],
"offsets": [
[
382,
391
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-10421629_T10"
}
]
},
{
"id": "PMID-10421629_E18",
"type": "Regulation",
"trigger": {
"text": [
"stabilizes"
],
"offsets": [
[
392,
402
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10421629_E17"
},
{
"role": "Theme",
"ref_id": "PMID-10421629_T11"
}
]
},
{
"id": "PMID-10421629_E19",
"type": "Pathway",
"trigger": {
"text": [
"signaling"
],
"offsets": [
[
458,
467
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-10421629_T12"
}
]
},
{
"id": "PMID-10421629_E20",
"type": "Regulation",
"trigger": {
"text": [
"regulates"
],
"offsets": [
[
468,
477
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T13"
},
{
"role": "Cause",
"ref_id": "PMID-10421629_E19"
}
]
},
{
"id": "PMID-10421629_E21",
"type": "Phosphorylation",
"trigger": {
"text": [
"dephosphorylated"
],
"offsets": [
[
530,
546
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T14"
}
]
},
{
"id": "PMID-10421629_E22",
"type": "Regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
550,
558
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_E21"
},
{
"role": "Cause",
"ref_id": "PMID-10421629_E23"
}
]
},
{
"id": "PMID-10421629_E23",
"type": "Pathway",
"trigger": {
"text": [
"signaling"
],
"offsets": [
[
566,
575
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-10421629_T15"
}
]
},
{
"id": "PMID-10421629_E24",
"type": "Dephosphorylation",
"trigger": {
"text": [
"dephosphorylated"
],
"offsets": [
[
581,
597
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T16"
}
]
},
{
"id": "PMID-10421629_E25",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
603,
608
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T16"
},
{
"role": "Theme",
"ref_id": "PMID-10421629_T17"
}
]
},
{
"id": "PMID-10421629_E26",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
648,
662
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T16"
}
]
},
{
"id": "PMID-10421629_E27",
"type": "Pathway",
"trigger": {
"text": [
"signaling"
],
"offsets": [
[
679,
688
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-10421629_T18"
}
]
},
{
"id": "PMID-10421629_E28",
"type": "Negative_regulation",
"trigger": {
"text": [
"lowers"
],
"offsets": [
[
689,
695
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_E29"
},
{
"role": "Cause",
"ref_id": "PMID-10421629_E27"
}
]
},
{
"id": "PMID-10421629_E29",
"type": "Binding",
"trigger": {
"text": [
"affinity"
],
"offsets": [
[
703,
711
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T20"
},
{
"role": "Theme",
"ref_id": "PMID-10421629_T19"
}
]
},
{
"id": "PMID-10421629_E30",
"type": "Negative_regulation",
"trigger": {
"text": [
"disengaging"
],
"offsets": [
[
738,
749
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_E31"
},
{
"role": "Cause",
"ref_id": "PMID-10421629_E28"
}
]
},
{
"id": "PMID-10421629_E31",
"type": "Degradation",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
772,
783
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10421629_T21"
}
]
}
] | [] | [] |
12 | PMID-10455013 | [
{
"id": "PMID-10455013__text",
"type": "abstract",
"text": [
"Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo. \n3-phosphoinositide-dependent protein kinase-1 (PDK1) expressed in unstimulated 293 cells was phosphorylated at Ser-25, Ser-241, Ser-393, Ser-396 and Ser-410 and the level of phosphorylation of each site was unaffected by stimulation with insulin-like growth factor-1. Mutation of Ser-241 to Ala abolished PDK1 activity, whereas mutation of the other phosphorylation sites individually to Ala did not affect PDK1 activity. Ser-241, unlike the other phosphorylation sites on PDK1, was resistant to dephosphorylation by protein phosphatase 2A(1). Ser-241 lies in the activation loop of the PDK1 kinase domain between subdomains VII and VIII in the equivalent position to the site that PDK1 phosphorylates on its protein kinase substrates. PDK1 expressed in bacteria was active and phosphorylated at Ser-241, suggesting that PDK1 can phosphorylate itself at this site, leading to its own activation.\n"
],
"offsets": [
[
0,
1061
]
]
}
] | [
{
"id": "PMID-10455013_T1",
"type": "Simple_chemical",
"offsets": [
[
19,
26
]
],
"text": [
"Ser-241"
],
"normalized": []
},
{
"id": "PMID-10455013_T2",
"type": "Gene_or_gene_product",
"offsets": [
[
60,
105
]
],
"text": [
"3-phosphoinositide-dependent protein kinase-1"
],
"normalized": []
},
{
"id": "PMID-10455013_T3",
"type": "Gene_or_gene_product",
"offsets": [
[
165,
210
]
],
"text": [
"3-phosphoinositide-dependent protein kinase-1"
],
"normalized": []
},
{
"id": "PMID-10455013_T4",
"type": "Gene_or_gene_product",
"offsets": [
[
212,
216
]
],
"text": [
"PDK1"
],
"normalized": []
},
{
"id": "PMID-10455013_T5",
"type": "Simple_chemical",
"offsets": [
[
276,
282
]
],
"text": [
"Ser-25"
],
"normalized": []
},
{
"id": "PMID-10455013_T6",
"type": "Simple_chemical",
"offsets": [
[
284,
291
]
],
"text": [
"Ser-241"
],
"normalized": []
},
{
"id": "PMID-10455013_T7",
"type": "Simple_chemical",
"offsets": [
[
293,
300
]
],
"text": [
"Ser-393"
],
"normalized": []
},
{
"id": "PMID-10455013_T8",
"type": "Simple_chemical",
"offsets": [
[
302,
309
]
],
"text": [
"Ser-396"
],
"normalized": []
},
{
"id": "PMID-10455013_T9",
"type": "Simple_chemical",
"offsets": [
[
314,
321
]
],
"text": [
"Ser-410"
],
"normalized": []
},
{
"id": "PMID-10455013_T10",
"type": "Gene_or_gene_product",
"offsets": [
[
403,
431
]
],
"text": [
"insulin-like growth factor-1"
],
"normalized": []
},
{
"id": "PMID-10455013_T11",
"type": "Simple_chemical",
"offsets": [
[
445,
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]
],
"text": [
"Ser-241"
],
"normalized": []
},
{
"id": "PMID-10455013_T12",
"type": "Simple_chemical",
"offsets": [
[
456,
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]
],
"text": [
"Ala"
],
"normalized": []
},
{
"id": "PMID-10455013_T13",
"type": "Gene_or_gene_product",
"offsets": [
[
470,
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]
],
"text": [
"PDK1"
],
"normalized": []
},
{
"id": "PMID-10455013_T14",
"type": "Simple_chemical",
"offsets": [
[
553,
556
]
],
"text": [
"Ala"
],
"normalized": []
},
{
"id": "PMID-10455013_T15",
"type": "Gene_or_gene_product",
"offsets": [
[
572,
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]
],
"text": [
"PDK1"
],
"normalized": []
},
{
"id": "PMID-10455013_T16",
"type": "Simple_chemical",
"offsets": [
[
587,
594
]
],
"text": [
"Ser-241"
],
"normalized": []
},
{
"id": "PMID-10455013_T17",
"type": "Gene_or_gene_product",
"offsets": [
[
638,
642
]
],
"text": [
"PDK1"
],
"normalized": []
},
{
"id": "PMID-10455013_T18",
"type": "Gene_or_gene_product",
"offsets": [
[
682,
707
]
],
"text": [
"protein phosphatase 2A(1)"
],
"normalized": []
},
{
"id": "PMID-10455013_T19",
"type": "Simple_chemical",
"offsets": [
[
709,
716
]
],
"text": [
"Ser-241"
],
"normalized": []
},
{
"id": "PMID-10455013_T20",
"type": "Gene_or_gene_product",
"offsets": [
[
752,
756
]
],
"text": [
"PDK1"
],
"normalized": []
},
{
"id": "PMID-10455013_T21",
"type": "Gene_or_gene_product",
"offsets": [
[
847,
851
]
],
"text": [
"PDK1"
],
"normalized": []
},
{
"id": "PMID-10455013_T22",
"type": "Gene_or_gene_product",
"offsets": [
[
901,
905
]
],
"text": [
"PDK1"
],
"normalized": []
},
{
"id": "PMID-10455013_T23",
"type": "Simple_chemical",
"offsets": [
[
961,
968
]
],
"text": [
"Ser-241"
],
"normalized": []
},
{
"id": "PMID-10455013_T24",
"type": "Gene_or_gene_product",
"offsets": [
[
986,
990
]
],
"text": [
"PDK1"
],
"normalized": []
}
] | [
{
"id": "PMID-10455013_E1",
"type": "Phosphorylation",
"trigger": {
"text": [
"Phosphorylation"
],
"offsets": [
[
0,
15
]
]
},
"arguments": [
{
"role": "Site",
"ref_id": "PMID-10455013_T1"
},
{
"role": "Theme",
"ref_id": "PMID-10455013_T2"
}
]
},
{
"id": "PMID-10455013_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"essential"
],
"offsets": [
[
30,
39
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T2"
},
{
"role": "Cause",
"ref_id": "PMID-10455013_E1"
}
]
},
{
"id": "PMID-10455013_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
218,
227
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T3"
}
]
},
{
"id": "PMID-10455013_E4",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
258,
272
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T3"
},
{
"role": "Site",
"ref_id": "PMID-10455013_T5"
}
]
},
{
"id": "PMID-10455013_E5",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
258,
272
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T3"
},
{
"role": "Site",
"ref_id": "PMID-10455013_T6"
}
]
},
{
"id": "PMID-10455013_E6",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
258,
272
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T3"
},
{
"role": "Site",
"ref_id": "PMID-10455013_T7"
}
]
},
{
"id": "PMID-10455013_E7",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
258,
272
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T3"
},
{
"role": "Site",
"ref_id": "PMID-10455013_T8"
}
]
},
{
"id": "PMID-10455013_E8",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
258,
272
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T3"
},
{
"role": "Site",
"ref_id": "PMID-10455013_T9"
}
]
},
{
"id": "PMID-10455013_E9",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
339,
354
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T3"
},
{
"role": "Site",
"ref_id": "PMID-10455013_T5"
}
]
},
{
"id": "PMID-10455013_E10",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
339,
354
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T3"
},
{
"role": "Site",
"ref_id": "PMID-10455013_T6"
}
]
},
{
"id": "PMID-10455013_E11",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
339,
354
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T3"
},
{
"role": "Site",
"ref_id": "PMID-10455013_T7"
}
]
},
{
"id": "PMID-10455013_E12",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
339,
354
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T3"
},
{
"role": "Site",
"ref_id": "PMID-10455013_T8"
}
]
},
{
"id": "PMID-10455013_E13",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
339,
354
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T3"
},
{
"role": "Site",
"ref_id": "PMID-10455013_T9"
}
]
},
{
"id": "PMID-10455013_E14",
"type": "Regulation",
"trigger": {
"text": [
"unaffected"
],
"offsets": [
[
372,
382
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10455013_T10"
},
{
"role": "Theme",
"ref_id": "PMID-10455013_E9"
}
]
},
{
"id": "PMID-10455013_E15",
"type": "Regulation",
"trigger": {
"text": [
"unaffected"
],
"offsets": [
[
372,
382
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10455013_T10"
},
{
"role": "Theme",
"ref_id": "PMID-10455013_E10"
}
]
},
{
"id": "PMID-10455013_E16",
"type": "Regulation",
"trigger": {
"text": [
"unaffected"
],
"offsets": [
[
372,
382
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10455013_T10"
},
{
"role": "Theme",
"ref_id": "PMID-10455013_E11"
}
]
},
{
"id": "PMID-10455013_E17",
"type": "Regulation",
"trigger": {
"text": [
"unaffected"
],
"offsets": [
[
372,
382
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10455013_T10"
},
{
"role": "Theme",
"ref_id": "PMID-10455013_E12"
}
]
},
{
"id": "PMID-10455013_E18",
"type": "Regulation",
"trigger": {
"text": [
"unaffected"
],
"offsets": [
[
372,
382
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10455013_T10"
},
{
"role": "Theme",
"ref_id": "PMID-10455013_E13"
}
]
},
{
"id": "PMID-10455013_E19",
"type": "Negative_regulation",
"trigger": {
"text": [
"resistant"
],
"offsets": [
[
648,
657
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_E20"
}
]
},
{
"id": "PMID-10455013_E20",
"type": "Dephosphorylation",
"trigger": {
"text": [
"dephosphorylation"
],
"offsets": [
[
661,
678
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10455013_T18"
},
{
"role": "Site",
"ref_id": "PMID-10455013_T16"
},
{
"role": "Theme",
"ref_id": "PMID-10455013_T17"
}
]
},
{
"id": "PMID-10455013_E21",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
906,
915
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T22"
}
]
},
{
"id": "PMID-10455013_E22",
"type": "Activation",
"trigger": {
"text": [
"active"
],
"offsets": [
[
932,
938
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T22"
}
]
},
{
"id": "PMID-10455013_E23",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
943,
957
]
]
},
"arguments": [
{
"role": "Site",
"ref_id": "PMID-10455013_T23"
},
{
"role": "Theme",
"ref_id": "PMID-10455013_T22"
}
]
},
{
"id": "PMID-10455013_E24",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylate"
],
"offsets": [
[
995,
1008
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T24"
},
{
"role": "Site",
"ref_id": "PMID-10455013_T23"
},
{
"role": "Cause",
"ref_id": "PMID-10455013_T24"
}
]
},
{
"id": "PMID-10455013_E25",
"type": "Positive_regulation",
"trigger": {
"text": [
"leading"
],
"offsets": [
[
1030,
1037
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_E26"
},
{
"role": "Cause",
"ref_id": "PMID-10455013_E24"
}
]
},
{
"id": "PMID-10455013_E26",
"type": "Activation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
1049,
1059
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10455013_T24"
}
]
}
] | [
{
"id": "PMID-10455013_1",
"entity_ids": [
"PMID-10455013_T3",
"PMID-10455013_T4"
]
}
] | [] |
13 | PMID-10487762 | [
{
"id": "PMID-10487762__text",
"type": "abstract",
"text": [
"NuA4, an essential transcription adaptor/histone H4 acetyltransferase complex containing Esa1p and the ATM-related cofactor Tra1p. \nPost-translational acetylation of histone H4 N-terminal tail in chromatin has been associated with several nuclear processes including transcription. We report the purification and characterization of a native multisubunit complex (NuA4) from yeast that acetylates nucleosomal histone H4. NuA4 has an apparent molecular mass of 1.3 MDa. All four conserved lysines of histone H4 can be acetylated by NuA4. We have identified the catalytic subunit of the complex as the product of ESA1, an essential gene required for cell cycle progression in yeast. Antibodies against Esa1p specifically immunoprecipitate NuA4 activity whereas the complex purified from a temperature-sensitive esa1 mutant loses its acetyltransferase activity at the restrictive temperature. Additionally, we have identified another subunit of the complex as the product of TRA1, an ATM-related essential gene homologous to human TRRAP, an essential cofactor for c-Myc- and E2F-mediated oncogenic transformation. Finally, the ability of NuA4 to stimulate GAL4-VP16-driven transcription from chromatin templates in vitro is also lost in the temperature-sensitive esa1 mutant. The function of the essential Esa1 protein as the HAT subunit of NuA4 and the presence of Tra1p, a putative transcription activator-interacting subunit, supports an essential link between nuclear H4 acetylation, transcriptional regulation and cell cycle control.\n"
],
"offsets": [
[
0,
1536
]
]
}
] | [
{
"id": "PMID-10487762_T1",
"type": "Complex",
"offsets": [
[
0,
4
]
],
"text": [
"NuA4"
],
"normalized": []
},
{
"id": "PMID-10487762_T2",
"type": "Gene_or_gene_product",
"offsets": [
[
19,
40
]
],
"text": [
"transcription adaptor"
],
"normalized": []
},
{
"id": "PMID-10487762_T3",
"type": "Gene_or_gene_product",
"offsets": [
[
41,
69
]
],
"text": [
"histone H4 acetyltransferase"
],
"normalized": []
},
{
"id": "PMID-10487762_T4",
"type": "Gene_or_gene_product",
"offsets": [
[
89,
94
]
],
"text": [
"Esa1p"
],
"normalized": []
},
{
"id": "PMID-10487762_T5",
"type": "Gene_or_gene_product",
"offsets": [
[
103,
106
]
],
"text": [
"ATM"
],
"normalized": []
},
{
"id": "PMID-10487762_T6",
"type": "Gene_or_gene_product",
"offsets": [
[
124,
129
]
],
"text": [
"Tra1p"
],
"normalized": []
},
{
"id": "PMID-10487762_T7",
"type": "Gene_or_gene_product",
"offsets": [
[
166,
176
]
],
"text": [
"histone H4"
],
"normalized": []
},
{
"id": "PMID-10487762_T8",
"type": "Cellular_component",
"offsets": [
[
196,
205
]
],
"text": [
"chromatin"
],
"normalized": []
},
{
"id": "PMID-10487762_T9",
"type": "Cellular_component",
"offsets": [
[
239,
246
]
],
"text": [
"nuclear"
],
"normalized": []
},
{
"id": "PMID-10487762_T10",
"type": "Complex",
"offsets": [
[
364,
368
]
],
"text": [
"NuA4"
],
"normalized": []
},
{
"id": "PMID-10487762_T11",
"type": "Cellular_component",
"offsets": [
[
397,
408
]
],
"text": [
"nucleosomal"
],
"normalized": []
},
{
"id": "PMID-10487762_T12",
"type": "Gene_or_gene_product",
"offsets": [
[
409,
419
]
],
"text": [
"histone H4"
],
"normalized": []
},
{
"id": "PMID-10487762_T13",
"type": "Complex",
"offsets": [
[
421,
425
]
],
"text": [
"NuA4"
],
"normalized": []
},
{
"id": "PMID-10487762_T14",
"type": "Simple_chemical",
"offsets": [
[
488,
495
]
],
"text": [
"lysines"
],
"normalized": []
},
{
"id": "PMID-10487762_T15",
"type": "Gene_or_gene_product",
"offsets": [
[
499,
509
]
],
"text": [
"histone H4"
],
"normalized": []
},
{
"id": "PMID-10487762_T16",
"type": "Complex",
"offsets": [
[
531,
535
]
],
"text": [
"NuA4"
],
"normalized": []
},
{
"id": "PMID-10487762_T17",
"type": "Gene_or_gene_product",
"offsets": [
[
611,
615
]
],
"text": [
"ESA1"
],
"normalized": []
},
{
"id": "PMID-10487762_T18",
"type": "Gene_or_gene_product",
"offsets": [
[
700,
705
]
],
"text": [
"Esa1p"
],
"normalized": []
},
{
"id": "PMID-10487762_T19",
"type": "Complex",
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[
737,
741
]
],
"text": [
"NuA4"
],
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},
{
"id": "PMID-10487762_T20",
"type": "Gene_or_gene_product",
"offsets": [
[
809,
813
]
],
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"esa1"
],
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},
{
"id": "PMID-10487762_T21",
"type": "Gene_or_gene_product",
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[
972,
976
]
],
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"TRA1"
],
"normalized": []
},
{
"id": "PMID-10487762_T22",
"type": "Gene_or_gene_product",
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[
981,
984
]
],
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"ATM"
],
"normalized": []
},
{
"id": "PMID-10487762_T23",
"type": "Gene_or_gene_product",
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[
1028,
1033
]
],
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"TRRAP"
],
"normalized": []
},
{
"id": "PMID-10487762_T24",
"type": "Gene_or_gene_product",
"offsets": [
[
1061,
1066
]
],
"text": [
"c-Myc"
],
"normalized": []
},
{
"id": "PMID-10487762_T25",
"type": "Gene_or_gene_product",
"offsets": [
[
1072,
1075
]
],
"text": [
"E2F"
],
"normalized": []
},
{
"id": "PMID-10487762_T26",
"type": "Complex",
"offsets": [
[
1135,
1139
]
],
"text": [
"NuA4"
],
"normalized": []
},
{
"id": "PMID-10487762_T27",
"type": "Gene_or_gene_product",
"offsets": [
[
1153,
1162
]
],
"text": [
"GAL4-VP16"
],
"normalized": []
},
{
"id": "PMID-10487762_T28",
"type": "Cellular_component",
"offsets": [
[
1189,
1198
]
],
"text": [
"chromatin"
],
"normalized": []
},
{
"id": "PMID-10487762_T29",
"type": "Gene_or_gene_product",
"offsets": [
[
1260,
1264
]
],
"text": [
"esa1"
],
"normalized": []
},
{
"id": "PMID-10487762_T30",
"type": "Gene_or_gene_product",
"offsets": [
[
1303,
1307
]
],
"text": [
"Esa1"
],
"normalized": []
},
{
"id": "PMID-10487762_T31",
"type": "Gene_or_gene_product",
"offsets": [
[
1323,
1326
]
],
"text": [
"HAT"
],
"normalized": []
},
{
"id": "PMID-10487762_T32",
"type": "Complex",
"offsets": [
[
1338,
1342
]
],
"text": [
"NuA4"
],
"normalized": []
},
{
"id": "PMID-10487762_T33",
"type": "Gene_or_gene_product",
"offsets": [
[
1363,
1368
]
],
"text": [
"Tra1p"
],
"normalized": []
},
{
"id": "PMID-10487762_T34",
"type": "Cellular_component",
"offsets": [
[
1461,
1468
]
],
"text": [
"nuclear"
],
"normalized": []
},
{
"id": "PMID-10487762_T35",
"type": "Gene_or_gene_product",
"offsets": [
[
1469,
1471
]
],
"text": [
"H4"
],
"normalized": []
}
] | [
{
"id": "PMID-10487762_E1",
"type": "Binding",
"trigger": {
"text": [
"containing"
],
"offsets": [
[
78,
88
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487762_T3"
},
{
"role": "Theme",
"ref_id": "PMID-10487762_T4"
},
{
"role": "Theme",
"ref_id": "PMID-10487762_T6"
}
]
},
{
"id": "PMID-10487762_E2",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
151,
162
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487762_T7"
}
]
},
{
"id": "PMID-10487762_E3",
"type": "Regulation",
"trigger": {
"text": [
"associated"
],
"offsets": [
[
215,
225
]
]
},
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{
"role": "Theme",
"ref_id": "PMID-10487762_E2"
}
]
},
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"id": "PMID-10487762_E4",
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"text": [
"acetylates"
],
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[
386,
396
]
]
},
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{
"role": "Theme",
"ref_id": "PMID-10487762_T12"
},
{
"role": "Cause",
"ref_id": "PMID-10487762_T10"
}
]
},
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"id": "PMID-10487762_E5",
"type": "Acetylation",
"trigger": {
"text": [
"acetylated"
],
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[
517,
527
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487762_T15"
},
{
"role": "Site",
"ref_id": "PMID-10487762_T14"
},
{
"role": "Cause",
"ref_id": "PMID-10487762_T16"
}
]
},
{
"id": "PMID-10487762_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
635,
643
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487762_E7"
},
{
"role": "Cause",
"ref_id": "PMID-10487762_T17"
}
]
},
{
"id": "PMID-10487762_E7",
"type": "Pathway",
"trigger": {
"text": [
"cell cycle"
],
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[
648,
658
]
]
},
"arguments": []
},
{
"id": "PMID-10487762_E8",
"type": "Regulation",
"trigger": {
"text": [
"related"
],
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[
985,
992
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10487762_T22"
},
{
"role": "Theme",
"ref_id": "PMID-10487762_E9"
}
]
},
{
"id": "PMID-10487762_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"essential"
],
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[
993,
1002
]
]
},
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{
"role": "Theme",
"ref_id": "PMID-10487762_T21"
}
]
},
{
"id": "PMID-10487762_E10",
"type": "Positive_regulation",
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"text": [
"supports"
],
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1426,
1434
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487762_E11"
},
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"role": "Cause",
"ref_id": "PMID-10487762_T30"
}
]
},
{
"id": "PMID-10487762_E11",
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"text": [
"essential"
],
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[
1438,
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]
]
},
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{
"role": "Theme",
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"link"
],
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]
},
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"role": "Cause",
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"role": "Theme",
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}
]
},
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"acetylation"
],
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]
]
},
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"role": "Theme",
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}
]
},
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]
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487762_E14"
}
]
}
] | [] | [] |
14 | PMID-10508167 | [
{
"id": "PMID-10508167__text",
"type": "abstract",
"text": [
"Two co-existing mechanisms for nuclear import of MAP kinase: passive diffusion of a monomer and active transport of a dimer. \nIn response to extracellular stimuli, mitogen-activated protein kinase (MAPK, also known as ERK) translocates from the cytoplasm to the nucleus. MAP kinase kinase (MAPKK, also know as MEK), which possesses a nuclear export signal (NES), acts as a cytoplasmic anchor of MAPK. Here we show evidence that tyrosine (Tyr190 in Xenopus MPK1/ERK2) phosphorylation of MAPK by MAPKK is necessary and sufficient for the dissociation of the MAPKK-MAPK complex, and that the dissociation of the complex is required for the nuclear translocation of MAPK. We then show that nuclear entry of MAPK through a nuclear pore occurs via two distinct mechanisms. Nuclear import of wild-type MAPK (mol. wt 42 kDa) was induced by activation of the MAPK pathway even in the presence of wheat germ agglutinin or dominant-negative Ran, whereas nuclear import of beta-galactosidase (beta-gal)-fused MAPK (mol. wt 160 kDa), which occurred in response to stimuli, was completely blocked by these inhibitors. Moreover, while a dimerization-deficient mutant of MAPK was able to translocate to the nucleus upon stimulation, this mutant MAPK, when fused to beta-gal, became unable to enter the nucleus. These results suggest that monomeric and dimeric forms of MAPK enter the nucleus by passive diffusion and active transport mechanisms, respectively.\n"
],
"offsets": [
[
0,
1444
]
]
}
] | [
{
"id": "PMID-10508167_T1",
"type": "Cellular_component",
"offsets": [
[
31,
38
]
],
"text": [
"nuclear"
],
"normalized": []
},
{
"id": "PMID-10508167_T2",
"type": "Gene_or_gene_product",
"offsets": [
[
49,
59
]
],
"text": [
"MAP kinase"
],
"normalized": []
},
{
"id": "PMID-10508167_T3",
"type": "Gene_or_gene_product",
"offsets": [
[
164,
196
]
],
"text": [
"mitogen-activated protein kinase"
],
"normalized": []
},
{
"id": "PMID-10508167_T4",
"type": "Gene_or_gene_product",
"offsets": [
[
198,
202
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10508167_T5",
"type": "Gene_or_gene_product",
"offsets": [
[
218,
221
]
],
"text": [
"ERK"
],
"normalized": []
},
{
"id": "PMID-10508167_T6",
"type": "Cellular_component",
"offsets": [
[
245,
254
]
],
"text": [
"cytoplasm"
],
"normalized": []
},
{
"id": "PMID-10508167_T7",
"type": "Cellular_component",
"offsets": [
[
262,
269
]
],
"text": [
"nucleus"
],
"normalized": []
},
{
"id": "PMID-10508167_T8",
"type": "Gene_or_gene_product",
"offsets": [
[
271,
288
]
],
"text": [
"MAP kinase kinase"
],
"normalized": []
},
{
"id": "PMID-10508167_T9",
"type": "Gene_or_gene_product",
"offsets": [
[
290,
295
]
],
"text": [
"MAPKK"
],
"normalized": []
},
{
"id": "PMID-10508167_T10",
"type": "Gene_or_gene_product",
"offsets": [
[
310,
313
]
],
"text": [
"MEK"
],
"normalized": []
},
{
"id": "PMID-10508167_T11",
"type": "Cellular_component",
"offsets": [
[
334,
341
]
],
"text": [
"nuclear"
],
"normalized": []
},
{
"id": "PMID-10508167_T12",
"type": "Cellular_component",
"offsets": [
[
373,
384
]
],
"text": [
"cytoplasmic"
],
"normalized": []
},
{
"id": "PMID-10508167_T13",
"type": "Gene_or_gene_product",
"offsets": [
[
395,
399
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10508167_T14",
"type": "Simple_chemical",
"offsets": [
[
428,
436
]
],
"text": [
"tyrosine"
],
"normalized": []
},
{
"id": "PMID-10508167_T15",
"type": "Simple_chemical",
"offsets": [
[
438,
444
]
],
"text": [
"Tyr190"
],
"normalized": []
},
{
"id": "PMID-10508167_T16",
"type": "Gene_or_gene_product",
"offsets": [
[
456,
460
]
],
"text": [
"MPK1"
],
"normalized": []
},
{
"id": "PMID-10508167_T17",
"type": "Gene_or_gene_product",
"offsets": [
[
461,
465
]
],
"text": [
"ERK2"
],
"normalized": []
},
{
"id": "PMID-10508167_T18",
"type": "Gene_or_gene_product",
"offsets": [
[
486,
490
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10508167_T19",
"type": "Gene_or_gene_product",
"offsets": [
[
494,
499
]
],
"text": [
"MAPKK"
],
"normalized": []
},
{
"id": "PMID-10508167_T20",
"type": "Complex",
"offsets": [
[
556,
566
]
],
"text": [
"MAPKK-MAPK"
],
"normalized": []
},
{
"id": "PMID-10508167_T21",
"type": "Cellular_component",
"offsets": [
[
637,
644
]
],
"text": [
"nuclear"
],
"normalized": []
},
{
"id": "PMID-10508167_T22",
"type": "Gene_or_gene_product",
"offsets": [
[
662,
666
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10508167_T23",
"type": "Cellular_component",
"offsets": [
[
686,
693
]
],
"text": [
"nuclear"
],
"normalized": []
},
{
"id": "PMID-10508167_T24",
"type": "Gene_or_gene_product",
"offsets": [
[
703,
707
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10508167_T25",
"type": "Cellular_component",
"offsets": [
[
718,
730
]
],
"text": [
"nuclear pore"
],
"normalized": []
},
{
"id": "PMID-10508167_T26",
"type": "Cellular_component",
"offsets": [
[
767,
774
]
],
"text": [
"Nuclear"
],
"normalized": []
},
{
"id": "PMID-10508167_T27",
"type": "Gene_or_gene_product",
"offsets": [
[
795,
799
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10508167_T28",
"type": "Gene_or_gene_product",
"offsets": [
[
850,
854
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10508167_T29",
"type": "Gene_or_gene_product",
"offsets": [
[
898,
908
]
],
"text": [
"agglutinin"
],
"normalized": []
},
{
"id": "PMID-10508167_T30",
"type": "Gene_or_gene_product",
"offsets": [
[
930,
933
]
],
"text": [
"Ran"
],
"normalized": []
},
{
"id": "PMID-10508167_T31",
"type": "Cellular_component",
"offsets": [
[
943,
950
]
],
"text": [
"nuclear"
],
"normalized": []
},
{
"id": "PMID-10508167_T32",
"type": "Gene_or_gene_product",
"offsets": [
[
961,
979
]
],
"text": [
"beta-galactosidase"
],
"normalized": []
},
{
"id": "PMID-10508167_T33",
"type": "Gene_or_gene_product",
"offsets": [
[
981,
989
]
],
"text": [
"beta-gal"
],
"normalized": []
},
{
"id": "PMID-10508167_T34",
"type": "Gene_or_gene_product",
"offsets": [
[
997,
1001
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10508167_T35",
"type": "Gene_or_gene_product",
"offsets": [
[
1155,
1159
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10508167_T36",
"type": "Cellular_component",
"offsets": [
[
1191,
1198
]
],
"text": [
"nucleus"
],
"normalized": []
},
{
"id": "PMID-10508167_T37",
"type": "Gene_or_gene_product",
"offsets": [
[
1229,
1233
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10508167_T38",
"type": "Gene_or_gene_product",
"offsets": [
[
1249,
1257
]
],
"text": [
"beta-gal"
],
"normalized": []
},
{
"id": "PMID-10508167_T39",
"type": "Cellular_component",
"offsets": [
[
1286,
1293
]
],
"text": [
"nucleus"
],
"normalized": []
},
{
"id": "PMID-10508167_T40",
"type": "Gene_or_gene_product",
"offsets": [
[
1353,
1357
]
],
"text": [
"MAPK"
],
"normalized": []
},
{
"id": "PMID-10508167_T41",
"type": "Cellular_component",
"offsets": [
[
1368,
1375
]
],
"text": [
"nucleus"
],
"normalized": []
}
] | [
{
"id": "PMID-10508167_E1",
"type": "Transport",
"trigger": {
"text": [
"import"
],
"offsets": [
[
39,
45
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508167_T2"
},
{
"role": "ToLoc",
"ref_id": "PMID-10508167_T1"
}
]
},
{
"id": "PMID-10508167_E2",
"type": "Transport",
"trigger": {
"text": [
"translocates"
],
"offsets": [
[
223,
235
]
]
},
"arguments": [
{
"role": "FromLoc",
"ref_id": "PMID-10508167_T6"
},
{
"role": "ToLoc",
"ref_id": "PMID-10508167_T7"
},
{
"role": "Theme",
"ref_id": "PMID-10508167_T3"
}
]
},
{
"id": "PMID-10508167_E3",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
467,
482
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508167_T18"
},
{
"role": "Cause",
"ref_id": "PMID-10508167_T19"
},
{
"role": "Site",
"ref_id": "PMID-10508167_T14"
}
]
},
{
"id": "PMID-10508167_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"necessary"
],
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[
503,
512
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508167_E5"
},
{
"role": "Cause",
"ref_id": "PMID-10508167_E3"
}
]
},
{
"id": "PMID-10508167_E5",
"type": "Dissociation",
"trigger": {
"text": [
"dissociation"
],
"offsets": [
[
536,
548
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508167_T20"
}
]
},
{
"id": "PMID-10508167_E6",
"type": "Dissociation",
"trigger": {
"text": [
"dissociation"
],
"offsets": [
[
589,
601
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508167_T20"
}
]
},
{
"id": "PMID-10508167_E7",
"type": "Positive_regulation",
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"text": [
"required"
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620,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508167_E8"
},
{
"role": "Cause",
"ref_id": "PMID-10508167_E6"
}
]
},
{
"id": "PMID-10508167_E8",
"type": "Transport",
"trigger": {
"text": [
"translocation"
],
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645,
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]
]
},
"arguments": [
{
"role": "ToLoc",
"ref_id": "PMID-10508167_T21"
},
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"role": "Theme",
"ref_id": "PMID-10508167_T22"
}
]
},
{
"id": "PMID-10508167_E9",
"type": "Transport",
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"text": [
"entry"
],
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694,
699
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508167_T24"
},
{
"role": "ToLoc",
"ref_id": "PMID-10508167_T23"
}
]
},
{
"id": "PMID-10508167_E10",
"type": "Transport",
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"text": [
"import"
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775,
781
]
]
},
"arguments": [
{
"role": "ToLoc",
"ref_id": "PMID-10508167_T26"
},
{
"role": "Theme",
"ref_id": "PMID-10508167_T27"
}
]
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"id": "PMID-10508167_E11",
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"text": [
"induced"
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]
]
},
"arguments": [
{
"role": "Cause",
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"role": "Theme",
"ref_id": "PMID-10508167_E10"
}
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},
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"text": [
"activation"
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]
]
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{
"role": "Theme",
"ref_id": "PMID-10508167_E13"
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},
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"pathway"
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"role": "Participant",
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"enter"
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]
},
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"role": "ToLoc",
"ref_id": "PMID-10508167_T41"
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{
"role": "Theme",
"ref_id": "PMID-10508167_T40"
}
]
}
] | [
{
"id": "PMID-10508167_1",
"entity_ids": [
"PMID-10508167_T3",
"PMID-10508167_T4",
"PMID-10508167_T5"
]
},
{
"id": "PMID-10508167_2",
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"PMID-10508167_T8",
"PMID-10508167_T9",
"PMID-10508167_T10"
]
},
{
"id": "PMID-10508167_3",
"entity_ids": [
"PMID-10508167_T16",
"PMID-10508167_T17"
]
},
{
"id": "PMID-10508167_4",
"entity_ids": [
"PMID-10508167_T32",
"PMID-10508167_T33"
]
}
] | [] |
15 | PMID-10508788 | [
{
"id": "PMID-10508788__text",
"type": "abstract",
"text": [
"The structure of phosphorylated p38gamma is monomeric and reveals a conserved activation-loop conformation. \nBACKGROUND: Mitogen-activated protein (MAP) kinases mediate the cellular response to stimuli such as pro-inflammatory cytokines and environmental stress. P38gamma is a new member of the MAP kinase family, and is expressed at its highest levels in skeletal muscle. P38gamma is 63% identical in sequence to P38alpha. The structure of P38alpha MAP kinase has been determined in the apo, unphosphorylated, inactive form. The structures of apo unphosphorylated ERK2, a related MAP kinase, and apo phosphorylated ERK2 have also been determined. RESULTS: We have determined the structure of doubly phosphorylated P38gamma in complex with an ATP analog by X-ray crystallography. This is the first report of a structure of an activated kinase in the P38 subfamily, and the first bound to a nucleotide. P38gamma residue phosphoryl-Thr183 forms hydrogen bonds with five basic amino acids, and these interactions induce an interdomain rotation. The conformation of the activation loop of P38gamma is almost identical to that observed in the structure of activated ERK2. However, unlike ERK2, the crystal structure and solution studies indicate that activated P38gamma exists as a monomer. CONCLUSIONS: Interactions mediated by phosphoryl-Thr183 induce structural changes that direct the domains and active-site residues of P38gamma into a conformation consistent with catalytic activity. The conformation of the phosphorylation loop is likely to be similar in all activated MAP kinases, but not all activated MAP kinases form dimers.\n"
],
"offsets": [
[
0,
1631
]
]
}
] | [
{
"id": "PMID-10508788_T1",
"type": "Gene_or_gene_product",
"offsets": [
[
32,
40
]
],
"text": [
"p38gamma"
],
"normalized": []
},
{
"id": "PMID-10508788_T2",
"type": "Gene_or_gene_product",
"offsets": [
[
121,
160
]
],
"text": [
"Mitogen-activated protein (MAP) kinases"
],
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},
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"id": "PMID-10508788_T3",
"type": "Gene_or_gene_product",
"offsets": [
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263,
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]
],
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"P38gamma"
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"id": "PMID-10508788_T4",
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295,
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]
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"MAP kinase"
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"offsets": [
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373,
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],
"text": [
"P38gamma"
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"id": "PMID-10508788_T6",
"type": "Gene_or_gene_product",
"offsets": [
[
414,
422
]
],
"text": [
"P38alpha"
],
"normalized": []
},
{
"id": "PMID-10508788_T7",
"type": "Gene_or_gene_product",
"offsets": [
[
441,
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]
],
"text": [
"P38alpha MAP kinase"
],
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},
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"id": "PMID-10508788_T8",
"type": "Gene_or_gene_product",
"offsets": [
[
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]
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"text": [
"ERK2"
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"id": "PMID-10508788_T9",
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]
],
"text": [
"MAP kinase"
],
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},
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"id": "PMID-10508788_T10",
"type": "Gene_or_gene_product",
"offsets": [
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616,
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]
],
"text": [
"ERK2"
],
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},
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"id": "PMID-10508788_T11",
"type": "Gene_or_gene_product",
"offsets": [
[
715,
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]
],
"text": [
"P38gamma"
],
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},
{
"id": "PMID-10508788_T12",
"type": "Simple_chemical",
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743,
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]
],
"text": [
"ATP"
],
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},
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"id": "PMID-10508788_T13",
"type": "Gene_or_gene_product",
"offsets": [
[
850,
853
]
],
"text": [
"P38"
],
"normalized": []
},
{
"id": "PMID-10508788_T14",
"type": "Gene_or_gene_product",
"offsets": [
[
902,
910
]
],
"text": [
"P38gamma"
],
"normalized": []
},
{
"id": "PMID-10508788_T15",
"type": "Simple_chemical",
"offsets": [
[
930,
936
]
],
"text": [
"Thr183"
],
"normalized": []
},
{
"id": "PMID-10508788_T16",
"type": "Simple_chemical",
"offsets": [
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943,
951
]
],
"text": [
"hydrogen"
],
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},
{
"id": "PMID-10508788_T17",
"type": "Gene_or_gene_product",
"offsets": [
[
1085,
1093
]
],
"text": [
"P38gamma"
],
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},
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"id": "PMID-10508788_T18",
"type": "Gene_or_gene_product",
"offsets": [
[
1161,
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]
],
"text": [
"ERK2"
],
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},
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"id": "PMID-10508788_T19",
"type": "Gene_or_gene_product",
"offsets": [
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1183,
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]
],
"text": [
"ERK2"
],
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},
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"id": "PMID-10508788_T20",
"type": "Gene_or_gene_product",
"offsets": [
[
1256,
1264
]
],
"text": [
"P38gamma"
],
"normalized": []
},
{
"id": "PMID-10508788_T21",
"type": "Simple_chemical",
"offsets": [
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1335,
1341
]
],
"text": [
"Thr183"
],
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},
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"id": "PMID-10508788_T22",
"type": "Gene_or_gene_product",
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1420,
1428
]
],
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"P38gamma"
],
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},
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"id": "PMID-10508788_T23",
"type": "Gene_or_gene_product",
"offsets": [
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1571,
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]
],
"text": [
"MAP kinases"
],
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},
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"id": "PMID-10508788_T24",
"type": "Gene_or_gene_product",
"offsets": [
[
1606,
1617
]
],
"text": [
"MAP kinases"
],
"normalized": []
}
] | [
{
"id": "PMID-10508788_E1",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
17,
31
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T1"
}
]
},
{
"id": "PMID-10508788_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
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321,
330
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T3"
}
]
},
{
"id": "PMID-10508788_E3",
"type": "Phosphorylation",
"trigger": {
"text": [
"unphosphorylated"
],
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[
493,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T7"
}
]
},
{
"id": "PMID-10508788_E4",
"type": "Activation",
"trigger": {
"text": [
"inactive"
],
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[
511,
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]
]
},
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{
"role": "Theme",
"ref_id": "PMID-10508788_T7"
}
]
},
{
"id": "PMID-10508788_E5",
"type": "Phosphorylation",
"trigger": {
"text": [
"unphosphorylated"
],
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548,
564
]
]
},
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{
"role": "Theme",
"ref_id": "PMID-10508788_T8"
}
]
},
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"id": "PMID-10508788_E6",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
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601,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T10"
}
]
},
{
"id": "PMID-10508788_E7",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
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700,
714
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T11"
}
]
},
{
"id": "PMID-10508788_E8",
"type": "Binding",
"trigger": {
"text": [
"complex"
],
"offsets": [
[
727,
734
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T11"
},
{
"role": "Theme",
"ref_id": "PMID-10508788_T12"
}
]
},
{
"id": "PMID-10508788_E9",
"type": "Activation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
826,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T13"
}
]
},
{
"id": "PMID-10508788_E10",
"type": "Binding",
"trigger": {
"text": [
"bound"
],
"offsets": [
[
879,
884
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T13"
},
{
"role": "Theme",
"ref_id": "PMID-10508788_T12"
}
]
},
{
"id": "PMID-10508788_E11",
"type": "Conversion",
"trigger": {
"text": [
"bonds"
],
"offsets": [
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952,
957
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T15"
}
]
},
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"id": "PMID-10508788_E12",
"type": "Conversion",
"trigger": {
"text": [
"interactions"
],
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997,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T15"
}
]
},
{
"id": "PMID-10508788_E13",
"type": "Activation",
"trigger": {
"text": [
"activated"
],
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1151,
1160
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T18"
}
]
},
{
"id": "PMID-10508788_E14",
"type": "Activation",
"trigger": {
"text": [
"activated"
],
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[
1246,
1255
]
]
},
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{
"role": "Theme",
"ref_id": "PMID-10508788_T20"
}
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},
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"id": "PMID-10508788_E15",
"type": "Activation",
"trigger": {
"text": [
"activated"
],
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1561,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T23"
}
]
},
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"id": "PMID-10508788_E16",
"type": "Activation",
"trigger": {
"text": [
"activated"
],
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1596,
1605
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T24"
}
]
},
{
"id": "PMID-10508788_E17",
"type": "Binding",
"trigger": {
"text": [
"form dimers"
],
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1618,
1629
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10508788_T24"
}
]
}
] | [] | [] |
16 | PMID-10517323 | [
{
"id": "PMID-10517323__text",
"type": "abstract",
"text": [
"Regulated nuclear localisation of the yeast transcription factor Ace2p controls expression of chitinase (CTS1) in Saccharomyces cerevisiae. \nThe yeast transcription factor Ace2p regulates expression of the chitinase gene CTS1 in a cell cycle-dependent manner. Nuclear localisation of Ace2p is restricted to late M and early G phases of the mitotic cell cycle. We show here that this nuclear localisation is directly associated with regulation of CTS1 expression. Using a version of Ace2p tagged with a c-myc epitope, we show that the protein is excluded from the nucleus of cells during most phases of the mitotic cell cycle. A mutant derivative in which one threonine and two serine residues, which are candidate phosphorylation sites, were replaced by alanine (to mimic constitutive dephosphorylation) is localised in the nucleus throughout the cell cycle. The mechanism of localisation of Ace2p therefore involves regulation of its phosphorylation state, and closely resembles that used by the homologous transcription factor Swi5p. The wild-type Ace2 protein associates with Cdc28p in vivo, suggesting this may be the kinase that mediates the phosphorylation event. The stability of the protein is greatly reduced in a mutant that is constitutively localised to the nucleus, but is restored in a deletion derivative which remains in the cytoplasm. Ace2p is therefore controlled throughout the cell cycle at three levels: transcription, nuclear localisation, and proteolysis.\n"
],
"offsets": [
[
0,
1479
]
]
}
] | [
{
"id": "PMID-10517323_T1",
"type": "Cellular_component",
"offsets": [
[
10,
17
]
],
"text": [
"nuclear"
],
"normalized": []
},
{
"id": "PMID-10517323_T2",
"type": "Gene_or_gene_product",
"offsets": [
[
65,
70
]
],
"text": [
"Ace2p"
],
"normalized": []
},
{
"id": "PMID-10517323_T3",
"type": "Gene_or_gene_product",
"offsets": [
[
94,
103
]
],
"text": [
"chitinase"
],
"normalized": []
},
{
"id": "PMID-10517323_T4",
"type": "Gene_or_gene_product",
"offsets": [
[
105,
109
]
],
"text": [
"CTS1"
],
"normalized": []
},
{
"id": "PMID-10517323_T5",
"type": "Gene_or_gene_product",
"offsets": [
[
172,
177
]
],
"text": [
"Ace2p"
],
"normalized": []
},
{
"id": "PMID-10517323_T6",
"type": "Gene_or_gene_product",
"offsets": [
[
206,
215
]
],
"text": [
"chitinase"
],
"normalized": []
},
{
"id": "PMID-10517323_T7",
"type": "Gene_or_gene_product",
"offsets": [
[
221,
225
]
],
"text": [
"CTS1"
],
"normalized": []
},
{
"id": "PMID-10517323_T8",
"type": "Cellular_component",
"offsets": [
[
260,
267
]
],
"text": [
"Nuclear"
],
"normalized": []
},
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"id": "PMID-10517323_T9",
"type": "Gene_or_gene_product",
"offsets": [
[
284,
289
]
],
"text": [
"Ace2p"
],
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},
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"id": "PMID-10517323_T10",
"type": "Cellular_component",
"offsets": [
[
383,
390
]
],
"text": [
"nuclear"
],
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},
{
"id": "PMID-10517323_T11",
"type": "Gene_or_gene_product",
"offsets": [
[
446,
450
]
],
"text": [
"CTS1"
],
"normalized": []
},
{
"id": "PMID-10517323_T12",
"type": "Gene_or_gene_product",
"offsets": [
[
482,
487
]
],
"text": [
"Ace2p"
],
"normalized": []
},
{
"id": "PMID-10517323_T13",
"type": "Gene_or_gene_product",
"offsets": [
[
502,
507
]
],
"text": [
"c-myc"
],
"normalized": []
},
{
"id": "PMID-10517323_T14",
"type": "Cellular_component",
"offsets": [
[
563,
570
]
],
"text": [
"nucleus"
],
"normalized": []
},
{
"id": "PMID-10517323_T15",
"type": "Simple_chemical",
"offsets": [
[
659,
668
]
],
"text": [
"threonine"
],
"normalized": []
},
{
"id": "PMID-10517323_T16",
"type": "Simple_chemical",
"offsets": [
[
677,
683
]
],
"text": [
"serine"
],
"normalized": []
},
{
"id": "PMID-10517323_T17",
"type": "Simple_chemical",
"offsets": [
[
754,
761
]
],
"text": [
"alanine"
],
"normalized": []
},
{
"id": "PMID-10517323_T18",
"type": "Cellular_component",
"offsets": [
[
824,
831
]
],
"text": [
"nucleus"
],
"normalized": []
},
{
"id": "PMID-10517323_T19",
"type": "Gene_or_gene_product",
"offsets": [
[
892,
897
]
],
"text": [
"Ace2p"
],
"normalized": []
},
{
"id": "PMID-10517323_T20",
"type": "Gene_or_gene_product",
"offsets": [
[
1029,
1034
]
],
"text": [
"Swi5p"
],
"normalized": []
},
{
"id": "PMID-10517323_T21",
"type": "Gene_or_gene_product",
"offsets": [
[
1050,
1054
]
],
"text": [
"Ace2"
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1341,
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"nuclear"
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}
] | [
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]
]
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"role": "Theme",
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"cell cycle"
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]
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"associated"
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]
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"regulation"
],
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]
]
},
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"role": "Theme",
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"expression"
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]
]
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"role": "Theme",
"ref_id": "PMID-10517323_T11"
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"cell cycle"
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]
]
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},
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"cell cycle"
],
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]
]
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},
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"localisation"
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"text": [
"involves"
],
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908,
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]
]
},
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"role": "Cause",
"ref_id": "PMID-10517323_E20"
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"regulation"
],
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]
]
},
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"role": "Theme",
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},
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"type": "Phosphorylation",
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"text": [
"phosphorylation"
],
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]
]
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"role": "Theme",
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],
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]
]
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"role": "Cause",
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]
]
},
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]
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"type": "Degradation",
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"proteolysis"
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]
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"arguments": [
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"role": "Theme",
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}
]
}
] | [] | [] |
17 | PMID-10523842 | [
{
"id": "PMID-10523842__text",
"type": "abstract",
"text": [
"Role of two upstream open reading frames in the translational control of oncogene mdm2. \nOverexpression of oncoprotein MDM2 has been found in a significant number of human soft tissue tumors. In a subset of these tumors, overexpression is a result of enhanced translation of mdm2 mRNA. There are two transcripts from the mdm2 gene that differ only in their 5' leaders: a long form (L-mdm2) and a short form (S-mdm2) that arise from the use of different promoters. L-mdm2 mRNA contains two upstream open reading frames (uORFs) and this mRNA was loaded with ribosomes inefficiently in comparison with S-mdm2. The 5' leader of L-mdm2 was sufficient to transfer translational repression to a reporter gene and the two uORFs acted synergistically to achieve full suppression. In contrast, the 5' leader of S-mdm2 allowed efficient translation of an attached reporter gene in the tumor cells. These results are consistent with a model in which overexpression of MDM2 in certain tumors results from a change in mRNA structure due to a switch in promoter usage.\n"
],
"offsets": [
[
0,
1054
]
]
}
] | [
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"id": "PMID-10523842_T1",
"type": "Gene_or_gene_product",
"offsets": [
[
82,
86
]
],
"text": [
"mdm2"
],
"normalized": []
},
{
"id": "PMID-10523842_T2",
"type": "Gene_or_gene_product",
"offsets": [
[
119,
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]
],
"text": [
"MDM2"
],
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},
{
"id": "PMID-10523842_T3",
"type": "Gene_or_gene_product",
"offsets": [
[
275,
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]
],
"text": [
"mdm2"
],
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},
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"id": "PMID-10523842_T4",
"type": "Gene_or_gene_product",
"offsets": [
[
321,
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]
],
"text": [
"mdm2"
],
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},
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"id": "PMID-10523842_T5",
"type": "Gene_or_gene_product",
"offsets": [
[
382,
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]
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"text": [
"L-mdm2"
],
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},
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"id": "PMID-10523842_T6",
"type": "Gene_or_gene_product",
"offsets": [
[
408,
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]
],
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"S-mdm2"
],
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"type": "Gene_or_gene_product",
"offsets": [
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464,
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]
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"L-mdm2"
],
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]
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"S-mdm2"
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]
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"L-mdm2"
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801,
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]
],
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"S-mdm2"
],
"normalized": []
},
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"type": "Gene_or_gene_product",
"offsets": [
[
956,
960
]
],
"text": [
"MDM2"
],
"normalized": []
}
] | [
{
"id": "PMID-10523842_E1",
"type": "Translation",
"trigger": {
"text": [
"translational"
],
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[
48,
61
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10523842_T1"
}
]
},
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"id": "PMID-10523842_E2",
"type": "Regulation",
"trigger": {
"text": [
"control"
],
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[
62,
69
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10523842_E1"
}
]
},
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"id": "PMID-10523842_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"Overexpression"
],
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[
89,
103
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10523842_T2"
}
]
},
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"type": "Gene_expression",
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"text": [
"overexpression"
],
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[
221,
235
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10523842_T2"
}
]
},
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"id": "PMID-10523842_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"result"
],
"offsets": [
[
241,
247
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10523842_E6"
},
{
"role": "Theme",
"ref_id": "PMID-10523842_E4"
}
]
},
{
"id": "PMID-10523842_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
251,
259
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10523842_E7"
}
]
},
{
"id": "PMID-10523842_E7",
"type": "Translation",
"trigger": {
"text": [
"translation"
],
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[
260,
271
]
]
},
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{
"role": "Theme",
"ref_id": "PMID-10523842_T3"
}
]
},
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"id": "PMID-10523842_E8",
"type": "Transcription",
"trigger": {
"text": [
"loaded with ribosomes"
],
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[
544,
565
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10523842_T7"
}
]
},
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"id": "PMID-10523842_E9",
"type": "Transcription",
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"text": [
"loaded with ribosomes"
],
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544,
565
]
]
},
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{
"role": "Theme",
"ref_id": "PMID-10523842_T8"
}
]
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"type": "Gene_expression",
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"text": [
"overexpression"
],
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[
938,
952
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10523842_T11"
}
]
}
] | [] | [] |
18 | PMID-10542212 | [
{
"id": "PMID-10542212__text",
"type": "abstract",
"text": [
"Interleukin-10 signaling blocks inhibitor of kappaB kinase activity and nuclear factor kappaB DNA binding. \nThe transcription factor nuclear factor kappaB (NF-kappaB) coordinates the activation of numerous genes in response to pathogens and proinflammatory cytokines and is, therefore, pivotal in the development of acute and chronic inflammatory diseases. In its inactive state, NF-kappaB is constitutively present in the cytoplasm as a p50-p65 heterodimer bound to its inhibitory protein IkappaB. Proinflammatory cytokines, such as tumor necrosis factor (TNF), activate NF-kappaB by stimulating the activity of the IkappaB kinases (IKKs) which phosphorylate IkappaBalpha on serine residues 32 and 36, targeting it for rapid degradation by the 26 S proteasome. This enables the release and nuclear translocation of the NF-kappaB complex and activation of gene transcription. Interleukin-10 (IL-10) is a pleiotropic cytokine that controls inflammatory processes by suppressing the production of proinflammatory cytokines which are known to be transcriptionally controlled by NF-kappaB. Conflicting data exists on the effects of IL-10 on TNF- and LPS-induced NF-kappaB activity in human monocytes and the molecular mechanisms involved have not been elucidated. In this study, we show that IL-10 functions to block NF-kappaB activity at two levels: 1) through the suppression of IKK activity and 2) through the inhibition of NF-kappaB DNA binding activity. This is the first evidence of an anti-inflammatory protein inhibiting IKK activity and demonstrates that IKK is a logical target for blocking inflammatory diseases.\n"
],
"offsets": [
[
0,
1620
]
]
}
] | [
{
"id": "PMID-10542212_T1",
"type": "Gene_or_gene_product",
"offsets": [
[
0,
14
]
],
"text": [
"Interleukin-10"
],
"normalized": []
},
{
"id": "PMID-10542212_T2",
"type": "Complex",
"offsets": [
[
32,
58
]
],
"text": [
"inhibitor of kappaB kinase"
],
"normalized": []
},
{
"id": "PMID-10542212_T3",
"type": "Complex",
"offsets": [
[
72,
93
]
],
"text": [
"nuclear factor kappaB"
],
"normalized": []
},
{
"id": "PMID-10542212_T4",
"type": "Complex",
"offsets": [
[
133,
154
]
],
"text": [
"nuclear factor kappaB"
],
"normalized": []
},
{
"id": "PMID-10542212_T5",
"type": "Complex",
"offsets": [
[
156,
165
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10542212_T6",
"type": "Complex",
"offsets": [
[
380,
389
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10542212_T7",
"type": "Cellular_component",
"offsets": [
[
423,
432
]
],
"text": [
"cytoplasm"
],
"normalized": []
},
{
"id": "PMID-10542212_T8",
"type": "Complex",
"offsets": [
[
438,
445
]
],
"text": [
"p50-p65"
],
"normalized": []
},
{
"id": "PMID-10542212_T9",
"type": "Gene_or_gene_product",
"offsets": [
[
490,
497
]
],
"text": [
"IkappaB"
],
"normalized": []
},
{
"id": "PMID-10542212_T10",
"type": "Gene_or_gene_product",
"offsets": [
[
534,
555
]
],
"text": [
"tumor necrosis factor"
],
"normalized": []
},
{
"id": "PMID-10542212_T11",
"type": "Gene_or_gene_product",
"offsets": [
[
557,
560
]
],
"text": [
"TNF"
],
"normalized": []
},
{
"id": "PMID-10542212_T12",
"type": "Complex",
"offsets": [
[
572,
581
]
],
"text": [
"NF-kappaB"
],
"normalized": []
},
{
"id": "PMID-10542212_T13",
"type": "Complex",
"offsets": [
[
617,
632
]
],
"text": [
"IkappaB kinases"
],
"normalized": []
},
{
"id": "PMID-10542212_T14",
"type": "Complex",
"offsets": [
[
634,
638
]
],
"text": [
"IKKs"
],
"normalized": []
},
{
"id": "PMID-10542212_T15",
"type": "Gene_or_gene_product",
"offsets": [
[
660,
672
]
],
"text": [
"IkappaBalpha"
],
"normalized": []
},
{
"id": "PMID-10542212_T16",
"type": "Simple_chemical",
"offsets": [
[
676,
694
]
],
"text": [
"serine residues 32"
],
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] | [] |
19 | PMID-10556521 | [
{
"id": "PMID-10556521__text",
"type": "abstract",
"text": [
"Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2. \nTwo sodium-dependent vitamin C transporters, hSVCT1 and hSVCT2, were cloned from a human kidney cDNA library. hSVCT1 had a 1797 bp open reading frame encoding a 598 amino acid polypeptide. The 1953 bp open reading frame of hSVCT2 encoded a 650 amino acid polypeptide. Using a Xenopus laevis oocyte expression system, both transporters were functionally expressed. By Eadie-Hofstee transformation the apparent K(m) of hSVCT1 for ascorbate was 252.0 microM and of hSVCT2 for ascorbate was 21.3 microM. Both transporters were sodium-dependent and did not transport dehydroascorbic acid. Incubation of oocytes expressing either transporter with phorbol 12-myristate 13-acetate (PMA) inhibited ascorbate transport activity. Availability of the human transporter clones may facilitate new strategies for determining vitamin C intake.\n"
],
"offsets": [
[
0,
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]
]
}
] | [
{
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]
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"text": [
"sodium"
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{
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104,
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[
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586,
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[
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],
"text": [
"vitamin C"
],
"normalized": []
}
] | [
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Dataset Card for BioNLP 2013 PC
the Pathway Curation (PC) task is a main event extraction task of the BioNLP shared task (ST) 2013. The PC task concerns the automatic extraction of biomolecular reactions from text. The task setting, representation and semantics are defined with respect to pathway model standards and ontologies (SBML, BioPAX, SBO) and documents selected by relevance to specific model reactions. Two BioNLP ST 2013 participants successfully completed the PC task. The highest achieved F-score, 52.8%, indicates that event extraction is a promising approach to supporting pathway curation efforts.
Citation Information
@inproceedings{ohta-etal-2013-overview,
title = "Overview of the Pathway Curation ({PC}) task of {B}io{NLP} Shared Task 2013",
author = "Ohta, Tomoko and
Pyysalo, Sampo and
Rak, Rafal and
Rowley, Andrew and
Chun, Hong-Woo and
Jung, Sung-Jae and
Choi, Sung-Pil and
Ananiadou, Sophia and
Tsujii, Jun{'}ichi",
booktitle = "Proceedings of the {B}io{NLP} Shared Task 2013 Workshop",
month = aug,
year = "2013",
address = "Sofia, Bulgaria",
publisher = "Association for Computational Linguistics",
url = "https://aclanthology.org/W13-2009",
pages = "67--75",
}
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