Regulation of insulin receptor substrate-1 expression levels by caveolin-1

The insulin receptor substrate‐1 (IRS‐1), a docking protein of the type 1 insulin‐like growth factor receptor (IGF‐IR) plays a significant role in cell proliferation and differentiation. The expression of IRS‐1 is down‐regulated in mouse embryo fibroblasts (MEFs) with a deletion of caveolin‐1 (cav1)...

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Veröffentlicht in:Journal of cellular physiology Jg. 217; H. 1; S. 281 - 289
Hauptverfasser: Chen, Jia, Capozza, Franco, Wu, An, deAngelis, Tiziana, Sun, Hongzhi, Lisanti, Michael, Baserga, Renato
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2008
Schlagworte:
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Animals
Blotting, Western
Caveolin 1 - metabolism
Cell Differentiation - physiology
Cell Proliferation
Down-Regulation
Embryo, Mammalian
Fibroblasts - cytology
Fibroblasts - metabolism
Gene Expression
Gene Expression Regulation
Immunoprecipitation
Insulin Receptor Substrate Proteins
Mice
Mice, Knockout
RNA Interference
RNA, Messenger - analysis
RNA, Small Interfering
Transfection
ISSN:0021-9541, 1097-4652, 1097-4652
Online-Zugang:Volltext
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Zusammenfassung:The insulin receptor substrate‐1 (IRS‐1), a docking protein of the type 1 insulin‐like growth factor receptor (IGF‐IR) plays a significant role in cell proliferation and differentiation. The expression of IRS‐1 is down‐regulated in mouse embryo fibroblasts (MEFs) with a deletion of caveolin‐1 (cav1) genes (KO cells). Levels of IRS‐1 mRNA are not affected. Re‐introduction of cav1 into KO cells rescues IRS‐1 expression. Stabilization of protein levels is reciprocal and a strict correlation between IRS‐1 and cav1 levels was confirmed in five cell lines, and in mouse tissues. IRS‐1 binds through its phosphotyrosine binding (PTB) domain to tyrosine 14 (Y14) of cav1, the residue phosphorylated by IGF‐1 stimulation and by v‐src. The down‐regulation of IRS‐1 in cav−/− cells occurs via the proteasome pathway. These results indicate a novel mechanism for the regulation of IRS‐1 expression levels, an important finding in view of IRS‐1 role in cell proliferation and transformation. J. Cell. Physiol. 217: 281–289, 2008. © 2008 Wiley‐Liss, Inc.
Bibliographie:ArticleID:JCP21498
ark:/67375/WNG-M0W9VB1G-M
istex:04ED0CEDF2704BA6EFD1391CAFDAD9AAFC652FC7
National Institutes of Health - No. CA 089640; No. CA 78890
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0021-9541
1097-4652
1097-4652
DOI:10.1002/jcp.21498