Identification of the major SHPTP2-binding protein that is tyrosine-phosphorylated in response to insulin

Keishi Yamauchi, Vered Ribon, Alan R. Saltiel, Jeffrey E. Pessin

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Immunoprecipitation of the cytosolic Src homology 2 domain-containing protein-tyrosine phosphatase, SHPTP2, from insulin-stimulated 3T3L1 adipocytes or Chinese hamster ovary cells expressing the human insulin receptor resulted in the coimmunoprecipitation of a diffuse tyrosine-phosphorylated band in the 115-kDa protein region on SDS-polyacrylamide gels. Although platelet-derived growth factor induced the tyrosine phosphorylation of the platelet-derived growth factor receptor and SHPTP2, there was no significant increase in the coimmunoprecipitation of tyrosine-phosphorylated pp115 with SHPTP2. SHPTP2 was also associated with tyrosine-phosphorylated insulin receptor substrate-1, but this only accounted for <2% of the total immunoreactive SHPTP2 protein. Similarly, only a small fraction of the total amount of tyrosine-phosphorylated insulin receptor substrate-1 (<4%) was associated with SHPTP2. Expression and immunoprecipitation of a Myc epitope-tagged wild-type SHPTP2 (MycWT-SHPTP2) and a catalytically inactive point mutant of SHPTP2 (Myc-C/S-SHPTP2) also demonstrated an insulin-dependent association of SHPTP2 with tyrosinephosphorylated pp115. Furthermore, expression of the catalytically inactive SHPTP2 mutant resulted in a marked enhancement in the amount of coimmunoprecipitated tyrosine-phosphorylated pp115 compared with the expression of wild-type SHPTP2. These data indicate that the insulin-stimulated tyrosine-phosphorylated 115-kDa protein is the predominant in vivo SHPTP2-binding protein and that pp115 may function as a physiological substrate for the SHPTP2 proteintyrosine phosphatase.

Original languageEnglish (US)
Pages (from-to)17716-17722
Number of pages7
JournalJournal of Biological Chemistry
Volume270
Issue number30
DOIs
StatePublished - Jul 28 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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