Epidermal Growth Factor-induced Association of the SHPTP2 Protein Tyrosine Phosphatase with a 115-kDa Phosphotyrosine Protein

Abstract

Epidermal growth factor (EGF) stimulation of HepG2 and NIH 3T3 cells expressing high levels of the human EGF receptor (3T3/ER) resulted in the tyrosine phosphorylation of a 115-kDa protein that was co-immunoprecipitated with the Src homology 2 (SH2) domain containing protein tyrosine phosphatase, SHPTP2. In contrast, activation of the EGF receptor resulted in a relatively low level (< 1%) of the total SHPTP2 pool associated with the tyrosine-autophosphorylated EGF receptor itself. Similarly, quantitative immunoprecipitations also demonstrated that only trace amounts of the total EGF receptor pool were associated with SHPTP2. Further, activation of the EGF receptor did not result in any significant tyrosine phosphorylation of SHPTP2 and/or the association of the 115-kDa protein with Grb2. In comparison, activation of Jurkat cells with a T cell receptor agonist monoclonal antibody resulted in the co-immunoprecipitation of a 120-kDa tyrosine-phosphorylated protein with Grb2 and a 105-kDa protein with SHPTP2. Thus, these data have identified the 115- and 105-kDa proteins as the predominant SHPTP2-associated phosphotyrosine proteins in EGF- and T cell receptor-activated cells, respectively.