Linked Life Data

20226764

Source:http://linkedlifedata.com/resource/pubmed/id/20226764

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-4-12
pubmed:abstractText
The insulin receptor substrate (IRS) proteins are major substrates of both insulin receptor and insulin-like growth factor (IGF)-I receptor tyrosine kinases. Previously, we reported that IRS-3 is localized to both cytosol and nucleus, and possesses transcriptional activity. In the present study, we identified Bcl-3 as a novel binding protein to IRS-3. Bcl-3 is a nuclear protein, which forms a complex with the homodimer of p50 NF-kappaB, leading to enhancement of transcription through p50 NF-kappaB. We found that Bcl-3 interacts with the pleckstrin homology domain and the phosphotyrosine binding domain of IRS-3, and that IRS-3 interacts with the ankyrin repeat domain of Bcl-3. In addition, IRS-3 augmented the binding activity of p50 to the NF-kappaB DNA binding site, as well as the tumor necrosis factor (TNF)-alpha-induced transcriptional activity of NF-kappaB. Lastly, IRS-3 enhanced NF-kappaB-dependent anti-apoptotic gene induction and consequently inhibited TNF-alpha-induced cell death. This series of results proposes a novel function for IRS-3 as a transcriptional regulator in TNF-alpha signaling, distinct from its function as a substrate of insulin/IGF receptor kinases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1090-2104
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
394
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
697-702
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Insulin receptor substrate-3, interacting with Bcl-3, enhances p50 NF-kappaB activity.
pubmed:affiliation
Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't