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 (pp125FAK) 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 pp125FAK.
Dates
Type | When |
---|---|
Created | 19 years, 3 months ago (May 31, 2006, 4:26 a.m.) |
Deposited | 3 years, 4 months ago (April 13, 2022, 1:59 p.m.) |
Indexed | 2 months ago (July 2, 2025, 2:32 p.m.) |
Issued | 30 years, 7 months ago (Jan. 31, 1995) |
Published | 30 years, 7 months ago (Jan. 31, 1995) |
Published Online | 30 years, 7 months ago (Jan. 31, 1995) |
Published Print | 30 years, 7 months ago (Jan. 31, 1995) |
@article{Yamauchi_1995, title={Protein-tyrosine-phosphatase SHPTP2 is a required positive effector for insulin downstream signaling.}, volume={92}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.92.3.664}, DOI={10.1073/pnas.92.3.664}, number={3}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Yamauchi, K and Milarski, K L and Saltiel, A R and Pessin, J E}, year={1995}, month=jan, pages={664–668} }