Protein-tyrosine-phosphatase SHPTP2 is a required positive effector for insulin downstream signaling

Keishi Yamauchi, Kim L. Milarski, Alan R. Saltiel, Jeffrey E. Pessin

Research output: Contribution to journalArticle

263 Scopus citations

Abstract

SHPTP2 is a ubiquitously expressed tyrosine-specific protein phosphatase that contains two amino-terminal Src homology 2 (SH2) domains responsible for its association with tyrosine-phosphorylated proteins. In this study, expression of dominant interfering mutants of SHPTP2 was found to inhibit insulin stimulation of c-fos reporter gene expression and activation of the 42-kDa (Erk2) and 44-kDa (Erk1) mitogen-activated protein kinases. Cotransfection of dominant interfering SHPTP2 mutants with v-Ras or Grb2 indicated that SHPTP2 regulated insulin signaling either upstream of or in parallel to Ras function. Furthermore, phosphotyrosine blotting and immunoprecipitation identified the 125-kDa focal adhesion kinase (pp125(FAK)) as a substrate for insulin-dependent tyrosine dephosphorylation. These data demonstrate that SHPTP2 functions as a positive regulator of insulin action and that insulin signaling results in the dephosphorylation of tyrosine- phosphorylated pp125(FAK).

Original languageEnglish (US)
Pages (from-to)664-668
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number3
DOIs
StatePublished - Jan 31 1995
Externally publishedYes

ASJC Scopus subject areas

  • General

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