Source:http://linkedlifedata.com/resource/pubmed/id/15284232
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
40
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| pubmed:dateCreated |
2004-9-27
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| pubmed:abstractText |
Interferon-gamma (IFNgamma) is a pluripotent cytokine whose major biological effects are mediated through a pathway in which STAT1 is the predominant and essential transcription factor. STAT3 can also be activated weakly by IFNgamma, but the mechanism of activation and function of STAT3 as a part of the interferon response are not known. Here we show that STAT3 activation is much stronger and more prolonged in STAT1-null mouse embryo fibroblasts than in wild-type cells. In response to IFNgamma, SRC-family kinases are required to activate STAT3 (but not STAT1) through tyrosine phosphorylation, whereas the receptor-bound kinases JAK1 and JAK2 are required to activate both STATs. Tyrosine 419 of the IFNgamma receptor subunit 1 (IFNGR1) is required to activate both STATs, suggesting that STAT1 and STAT3 compete with each other for the same receptor phosphotyrosine motif. Activated STAT3 can replace STAT1 in STAT1-null cells to drive the transcription of certain genes, for example, socs-3 and c/ebpdelta, which have gamma-activated sequence motifs in their promoters. Work from Ian Kerr's laboratory reveals that the gp130-linked interleukin-6 receptor, which usually activates STAT3 predominantly, activates STAT1 efficiently when STAT3 is absent. Because STAT1 and STAT3 have opposing biological effects (STAT3 is an oncogene, and STAT1 is a tumor suppressor), the reciprocal activation of these two transcription factors in response to IFNgamma or interleukin-6 suggests that their relative abundance, which may vary substantially in different normal cell types, under different conditions or in tumors is likely to have a major impact on how cells behave in response to different cytokines.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Socs3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stat1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
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| pubmed:volume |
279
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
41679-85
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:15284232-Animals,
pubmed-meshheading:15284232-DNA-Binding Proteins,
pubmed-meshheading:15284232-Fibroblasts,
pubmed-meshheading:15284232-Gene Expression Profiling,
pubmed-meshheading:15284232-Gene Expression Regulation,
pubmed-meshheading:15284232-Interferon-gamma,
pubmed-meshheading:15284232-Mice,
pubmed-meshheading:15284232-Mice, Knockout,
pubmed-meshheading:15284232-Phosphorylation,
pubmed-meshheading:15284232-Repressor Proteins,
pubmed-meshheading:15284232-STAT1 Transcription Factor,
pubmed-meshheading:15284232-STAT3 Transcription Factor,
pubmed-meshheading:15284232-Suppressor of Cytokine Signaling Proteins,
pubmed-meshheading:15284232-Trans-Activators,
pubmed-meshheading:15284232-Transcription Factors,
pubmed-meshheading:15284232-Tyrosine,
pubmed-meshheading:15284232-src-Family Kinases
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| pubmed:year |
2004
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| pubmed:articleTitle |
Alternative activation of STAT1 and STAT3 in response to interferon-gamma.
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| pubmed:affiliation |
Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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