Linked Life Data

10744748

Source:http://linkedlifedata.com/resource/pubmed/id/10744748

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2000-5-8
pubmed:abstractText
The insulin receptor substrate (IRS) family of proteins mediate a variety of intracellular signaling events by serving as signaling platforms downstream of several receptor tyrosine kinases including the insulin and insulin-like growth factor-1 (IGF-1) receptors. Recently, several new members of this family have been identified including IRS-3, IRS-4, and growth factor receptor-binding protein 2-associated binder-1 (Gab-1). 3T3 cell lines derived from IRS-1-deficient embryos exhibit a 70-80% reduction in IGF-1-stimulated S-phase entry and a parallel decrease in the induction of the immediate-early genes c-fos and egr-1 but unaltered activation of the mitogen-activated protein kinases extracellular signal-regulated kinase-1 and extracellular signal-regulated kinase-2. Reconstitution of IRS-1 expression in IRS-1-deficient fibroblasts by retroviral mediated gene transduction is capable of restoring these defects. Overexpression of Gab-1 in IRS-1-deficient fibroblasts also results in the restoration of egr-1 induction to levels similar to those achieved by IRS-1 reconstitution and markedly increases IGF-1-stimulated S-phase progression. Gab-1 is capable of regulating these biological end points despite the absence of IGF-1 stimulated tyrosine phosphorylation. These data provide evidence that Gab-1 may serve as a unique signaling intermediate in insulin/IGF-1 signaling for induction of early gene expression and stimulation of mitogenesis without direct tyrosine phosphorylation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10545-50
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10744748-3T3 Cells, pubmed-meshheading:10744748-Animals, pubmed-meshheading:10744748-Cell Division, pubmed-meshheading:10744748-Enzyme Activation, pubmed-meshheading:10744748-Epidermal Growth Factor, pubmed-meshheading:10744748-Female, pubmed-meshheading:10744748-Genetic Vectors, pubmed-meshheading:10744748-Insulin Receptor Substrate Proteins, pubmed-meshheading:10744748-Insulin-Like Growth Factor I, pubmed-meshheading:10744748-Mice, pubmed-meshheading:10744748-Mice, Knockout, pubmed-meshheading:10744748-Mitogen-Activated Protein Kinases, pubmed-meshheading:10744748-Phosphoproteins, pubmed-meshheading:10744748-Phosphotyrosine, pubmed-meshheading:10744748-Recombinant Proteins, pubmed-meshheading:10744748-Retroviridae, pubmed-meshheading:10744748-Signal Transduction, pubmed-meshheading:10744748-Transfection
pubmed:year
2000
pubmed:articleTitle
Gab-1-mediated IGF-1 signaling in IRS-1-deficient 3T3 fibroblasts.
pubmed:affiliation
Division of Cellular and Molecular Physiology, Joslin Diabetes Center and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't