Identification of the major SHPTP2-binding protein that is tyrosine-phosphorylated in response to insulin.
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 (Myc-WT-SHPTP2) and a catalytically inactive point mutant of SHPTP2 (Myc-C/S-SHPTP2) also demonstrated an insulin-dependent association of SHPTP2 with tyrosine-phosphorylated 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 protein-tyrosine phosphatase.
Mesh Terms:
3T3 Cells, Adaptor Proteins, Signal Transducing, Adipocytes, Amino Acid Sequence, Animals, CHO Cells, Catalysis, Cricetinae, GRB2 Adaptor Protein, Humans, Insulin, Intracellular Signaling Peptides and Proteins, Kinetics, Mice, Molecular Sequence Data, Mutation, Oncogene Proteins, Phosphoproteins, Phosphorylation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-crk, Tyrosine
3T3 Cells, Adaptor Proteins, Signal Transducing, Adipocytes, Amino Acid Sequence, Animals, CHO Cells, Catalysis, Cricetinae, GRB2 Adaptor Protein, Humans, Insulin, Intracellular Signaling Peptides and Proteins, Kinetics, Mice, Molecular Sequence Data, Mutation, Oncogene Proteins, Phosphoproteins, Phosphorylation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-crk, Tyrosine
J. Biol. Chem.
Date: Jul. 28, 1995
PubMed ID: 7629070
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