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

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Walsh, C. T. Bennett, A. M. Neel, B. G. Sugimoto, S. Tang, T. L.
Description	Author Affiliation: Bennett AM ( Molecular Medicine Unit, Beth Israel Hospital, Boston, MA 02215.);
Abstract	Protein-tyrosine-phosphatase SHPTP2 (Syp/PTP-1D/PTP2C) is the homologue of the Drosophila corkscrew (csw) gene product, which transmits positive signals from receptor tyrosine kinases. Likewise, SHPTP2 has been implicated in positive signaling from platelet-derived growth factor receptor beta (PDGFR). Upon PDGF stimulation, SHPTP2 binds to the PDGFR and becomes tyrosine-phosphorylated. We have identified tyrosine-542 (pY542TNI) as the major in vivo site of SHPTP2 tyrosine phosphorylation. The pY542TNI sequence conforms to the consensus binding site for the SH2 domain of Grb2, which, by association with Sos1, couples some growth factor receptors to Ras. Following PDGF stimulation, Grb2 binds tyrosine-phosphorylated SHPTP2. Moreover, a mutant PDGFR lacking its SHPTP2 binding site displays markedly reduced Grb2 binding. These data indicate that phosphorylation of SHPTP2 couples Grb2 to PDGFR in vivo, providing a mechanism for Ras activation by PDGFR and for positive signaling via SHPTP2 and Csw.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	15
Volume Number	91
Language	English
Publisher	National Academy of Sciences
Publisher Date	1994-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Genes, Ras Protein Tyrosine Phosphatases Metabolism Receptors, Platelet-Derived Growth Factor 3T3 Cells Animals Binding Sites Cell Line DNA Intracellular Signaling Peptides And Proteins Mice Mice, Inbred BALB C Molecular Sequence Data Phosphorylation Protein Tyrosine Phosphatase, Non-Receptor Type 11 Protein Tyrosine Phosphatase, Non-Receptor Type 6 SH2 Domain-Containing Protein Tyrosine Phosphatases Signal Transduction Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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