ERYTHROPOIETIN-INDUCED RECRUITMENT OF SHC VIA A RECEPTOR PHOSPHOTYROSINE-INDEPENDENT, JAK2-ASSOCIATED PATHWAY
ERYTHROPOIETIN-INDUCED RECRUITMENT OF SHC VIA A RECEPTOR PHOSPHOTYROSINE-INDEPENDENT, JAK2-ASSOCIATED PATHWAY
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DOI：
10.1074/jbc.270.19.11055
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发表时间：
1995-05-12
影响因子：
4.8
通讯作者：
WOJCHOWSKI, DM
中科院分区：
文献类型：
--
作者：
HE, TC;JIANG, N;WOJCHOWSKI, DM
基于Shc作为I型细胞因子受体的信号传导效应物的最近牵连的作用，已经研究了在促红细胞生成素受体（EPOR）系统中介导Shc的募集和磷酸化的因子。稳定表达野生型鼠EPOR的FDC-P1细胞支持EPO诱导的Shc与Jak 2的结合及其快速酪氨酸磷酸化。然而，这并不依赖于磷酸酪氨酸位点内的EPOR的存在，并介导的有丝分裂缺陷型受体（EPOR 329）缺乏胞质酪氨酸残基。这一点通过Shc和Jak 2共免疫沉淀物的Western印迹以及通过对精氨酸诱导的Shc磷酸化的体外测定的开发来显示。Shc与Jak 2的直接关联也被观察到，并被证明取决于EPO暴露和Shc的SH 2子域。总之，这些研究表明，Jak 2，在一定程度上，可能介导EPO诱导的磷酸化的Shc。
Based on the recently implicated role of Shc as a signaling effector for type I cytokine receptors, factors which mediate the recruitment and phosphorylation of Shc in the erythropoietin receptor (EPOR) system have been studied. FDC-P1 cells stably expressing the wild type murine EPOR supported the EPO-induced association of Shc with Jak2 and its rapid tyrosine phosphorylation. However, this did not depend upon the presence of phosphotyrosine sites within the EPOR and was mediated by a mitogenically deficient receptor form (EPOR329) lacking cytoplasmic tyrosine residues. This was shown both by Western blotting of Shc and Jak2 co-immunoprecipitates and through the development of an in vitro assay for cytokine-induced Shc phosphorylation. The direct association of Shc with Jak2 also was observed and was shown to depend upon EPO-exposure and the SH2 subdomain of Shc. Together, these studies indicate that Jak2, in part, may mediate the EPO-induced phosphorylation of Shc.