Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras

作者: A. M. Bennett , T. L. Tang , S. Sugimoto , C. T. Walsh , B. G. Neel

DOI: 10.1073/PNAS.91.15.7335

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摘要: Abstract Protein-tyrosine-phosphatase SHPTP2 (Syp/PTP-1D/PTP2C) is the homologue of Drosophila corkscrew (csw) gene product, which transmits positive signals from receptor tyrosine kinases. Likewise, has been implicated in signaling platelet-derived growth factor beta (PDGFR). Upon PDGF stimulation, binds to PDGFR and becomes tyrosine-phosphorylated. We have identified tyrosine-542 (pY542TNI) as major vivo site phosphorylation. The pY542TNI sequence conforms consensus binding for SH2 domain Grb2, which, by association with Sos1, couples some receptors Ras. Following Grb2 tyrosine-phosphorylated SHPTP2. Moreover, a mutant lacking its displays markedly reduced binding. These data indicate that phosphorylation vivo, providing mechanism Ras activation via Csw.

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