rdf:type |
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lifeskim:mentions |
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pubmed:issue |
46
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pubmed:dateCreated |
1997-12-11
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pubmed:abstractText |
The signaling mechanisms utilized by the proinflammatory cytokine interleukin-1 (IL-1) to activate the transcription factors NFkappaB and activator protein-1 (AP-1) are poorly defined. We present evidence here that IL-1 not only stimulates a dramatic increase in phosphatidylinositol 3-kinase (PI 3-kinase) activity but also induces the physical interaction of its type I receptor with the p85 regulatory subunit of PI 3-kinase. Furthermore, two PI 3-kinase-specific inhibitors, wortmannin and a dominant-negative mutant of the p85 subunit, inhibited IL-1-induced activation of both NFkappaB and AP-1. Transient transfection experiments indicated that whereas overexpression of PI 3-kinase may be sufficient to induce AP-1 and increase nuclear c-Fos protein levels, PI 3-kinase may need to cooperate with other IL-1-inducible signals to fully activate NFkappaB-dependent gene expression. In this regard, cotransfection studies suggested that PI 3-kinase may functionally interact with the recently-identified IL-1-receptor-associated kinase to activate NFkappaB. Our results thus indicate that PI 3-kinase is a novel signal transducer in IL-1 signaling and that it may differentially mediate the activation of NFkappaB and AP-1.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Androstadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1 Receptor-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
272
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
29167-73
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:9360994-Androstadienes,
pubmed-meshheading:9360994-Catalysis,
pubmed-meshheading:9360994-Enzyme Activation,
pubmed-meshheading:9360994-Enzyme Inhibitors,
pubmed-meshheading:9360994-Gene Expression Regulation,
pubmed-meshheading:9360994-Genes, Reporter,
pubmed-meshheading:9360994-Humans,
pubmed-meshheading:9360994-Interleukin-1,
pubmed-meshheading:9360994-Interleukin-1 Receptor-Associated Kinases,
pubmed-meshheading:9360994-NF-kappa B,
pubmed-meshheading:9360994-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:9360994-Protein Binding,
pubmed-meshheading:9360994-Protein Kinases,
pubmed-meshheading:9360994-Receptors, Interleukin-1,
pubmed-meshheading:9360994-Signal Transduction,
pubmed-meshheading:9360994-Transcription Factor AP-1,
pubmed-meshheading:9360994-Tumor Cells, Cultured
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pubmed:year |
1997
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pubmed:articleTitle |
Phosphatidylinositol 3-kinase in interleukin 1 signaling. Physical interaction with the interleukin 1 receptor and requirement in NFkappaB and AP-1 activation.
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pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Box 117, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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