Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
1997-12-11
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29167-73
pubmed:dateRevised
2010-11-18
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
pubmed:year
1997
pubmed:articleTitle
Phosphatidylinositol 3-kinase in interleukin 1 signaling. Physical interaction with the interleukin 1 receptor and requirement in NFkappaB and AP-1 activation.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Box 117, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.