PROTEIN-TYROSINE-PHOSPHATASE SHPTP2 COUPLES PLATELET-DERIVED GROWTH-FACTOR RECEPTOR-BETA TO RAS
PROTEIN-TYROSINE-PHOSPHATASE SHPTP2 COUPLES PLATELET-DERIVED GROWTH-FACTOR RECEPTOR-BETA TO RAS
复制标题
DOI：
10.1073/pnas.91.15.7335
复制
发表时间：
1994-07-19
影响因子：
11.1
通讯作者：
NEEL, BG
中科院分区：
文献类型：
--
作者：
BENNETT, AM;TANG, TL;NEEL, BG
蛋白质酪氨酸磷酸酶SHPTP 2（Syp/PTP-1D/PTP 2C）是果蝇开瓶器（csw）基因产物的同源物，可传递来自受体酪氨酸激酶的正信号。同样，SHPTP 2与血小板衍生生长因子受体β（PDGFR）的阳性信号传导有关。在PDGF刺激后，SHPTP 2与PDGFR结合并变为酪氨酸磷酸化。我们已经确定了酪氨酸-542（pY（542）TNI），SHPTP 2酪氨酸磷酸化的主要体内位点。pY（542）TNI序列与Grb 2的SH 2结构域的共有结合位点一致，该结构域通过与Sos 1结合，将一些生长因子受体偶联至Ras。在PDGF刺激后，Grb 2结合酪氨酸磷酸化的SHPTP 2。此外，缺乏SHPTP 2结合位点的突变型PDGFR显示Grb 2结合显著降低。这些数据表明SHPTP 2的磷酸化在体内将Grb 2偶联至PDGFR，从而提供了PDGFR激活Ras以及通过SHPTP 2和Csw进行正信号传导的机制。
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.