PROTEIN-TYROSINE-PHOSPHATASE SHPTP2 COUPLES PLATELET-DERIVED GROWTH-FACTOR RECEPTOR-BETA TO RAS

被引：365

作者：

BENNETT, AM ^{[1
]}

TANG, TL ^{[1
]}

SUGIMOTO, S ^{[1
]}

WALSH, CT ^{[1
]}

NEEL, BG ^{[1
]}

机构：

[1] HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02215 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1994年 / 91卷 / 15期

关键词：

SRC HOMOLOGY 2; TYROSINE KINASE; SIGNAL TRANSDUCTION;

D O I：

10.1073/pnas.91.15.7335

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (pY(542)TNI), the major in vivo site of SHPTP2 tyrosine phosphorylation. The pY(542)TNI 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.

引用

页码：7335 / 7339

页数：5

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