SPECIFIC RECRUITMENT OF SH-PTP1 TO THE ERYTHROPOIETIN RECEPTOR CAUSES INACTIVATION OF JAK2 AND TERMINATION OF PROLIFERATIVE SIGNALS
SPECIFIC RECRUITMENT OF SH-PTP1 TO THE ERYTHROPOIETIN RECEPTOR CAUSES INACTIVATION OF JAK2 AND TERMINATION OF PROLIFERATIVE SIGNALS
复制标题
DOI：
10.1016/0092-8674(95)90351-8
复制
发表时间：
1995-03-10
期刊：
影响因子：
64.5
通讯作者：
LODISH, HF
中科院分区：
文献类型：
--
作者：
KLINGMULLER, U;LORENZ, U;LODISH, HF
促红细胞生成素（EPO）与其受体（EPO-R）的结合激活蛋白酪氨酸激酶JAK 2。JAK 2失活的机制尚不清楚。我们发现，造血蛋白酪氨酸磷酸酶SH-PTP 1（也称为HCP和PTP 1C）通过其SH 2结构域与酪氨酸磷酸化的EPO-R相关联。体外结合研究表明，EPO-R胞质结构域中的Y 429是SH-PTP 1的结合位点。缺乏Y 429的突变EPO-Rs不能结合SH-PTP 1;表达这种突变体的细胞对EPO超敏，并显示出延长的EPO诱导的JAK 2自磷酸化。我们的研究结果表明，SH-PTP 1的激活结合到EPO-R在终止增殖信号中起着重要作用。
The binding of erythropoietin (EPO) to its receptor (EPO-R) activates the protein tyrosine kinase JAK2. The mechanism of JAK2 inactivation has been unclear. We show that the hematopoietic protein tyrosine phosphatase SH-PTP1 (also called HCP and PTP1C) associates via its SH2 domains with the tyrosine-phosphorylated EPO-R. In vitro binding studies suggest that Y429 in the cytoplasmic domain of the EPO-R is the binding site for SH-PTP1. Mutant EPO-Rs lacking Y429 are unable to bind SH-PTP1; cells expressing such mutants are hypersensitive to EPO and display prolonged EPO-induced autophosphorylation of JAK2. Our results suggest that activation of SH-PTP1 by binding to the EPO-R plays a major role in terminating proliferative signals.