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

✍ Scribed by Jia Chen; Franco Capozza; An Wu; Tiziana deAngelis; Hongzhi Sun; Michael Lisanti; Renato Baserga

Publisher
John Wiley and Sons
Year
2008
Tongue
English
Weight
363 KB
Volume
217
Category
Article
ISSN
0021-9541

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✦ Synopsis

Abstract

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.

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