A complex of Grb2 adaptor protein, Sos exchange factor, and a 36-kDa membrane-bound tyrosine phosphoprotein is implicated in ras activation in T cells.
A complex of Grb2 adaptor protein, Sos exchange factor, and a 36-kDa membrane-bound tyrosine phosphoprotein is implicated in ras activation in T cells.
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Grb2 接头蛋白、Sos 交换因子和 36 kDa 膜结合酪氨酸磷蛋白的复合物参与 T 细胞中 ras 的激活。
DOI：
10.1016/s0021-9258(17)37070-9
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
J. Downward
中科院分区：
文献类型：
--
作者：
L. Buday;S. Egan;P. R. Viciana;D. Cantrell;J. Downward
T淋巴细胞含有Grb 2和Sos，Grb 2是含有衔接蛋白的SH 2和SH 3结构域，Sos是Ras的鸟嘌呤核苷酸交换因子。来自T细胞裂解物的Sos免疫沉淀物含有36-kDa蛋白，其响应于T细胞受体/CD 3交联而在酪氨酸残基上磷酸化。使用不同细菌合成的GST-Sos融合蛋白的体外研究证实了含有p36和富含脯氨酸的Sos COOH末端结构域的复合物的形成。其中两个SH 3结构域都已突变失活的突变GST-Grb 2蛋白的使用表明Grb 2通过其SH 2结构域与酪氨酸磷酸化的p36结合。在Jurkat细胞中，磷酸化的p36仅位于颗粒部分中。另外，另一种含有SH 2结构域的蛋白质p52 Shc在TCR. CD 3交联后被酪氨酸磷酸化，并与含有150-kDa磷酸酪氨酸的蛋白质缔合。总之，这些数据表明，通过TCR. CD 3复合物激活T细胞中的Ras可能至少部分地受到与成纤维细胞中发现的机制类似的机制的控制，在这种情况下，涉及Grb 2、Sos和分子量为36 kDa的膜结合酪氨酸磷蛋白的复合物的形成。
T lymphocytes contain both Grb2, an SH2 and SH3 domain containing adaptor protein, and Sos, a guanine nucleotide exchange factor for Ras. Immunoprecipitates of Sos from the lysates of T cells contain a 36-kDa protein which is phosphorylated on tyrosine residues in response to T cell receptor/CD3 cross-linking. In vitro studies using different bacterially synthesized GST-Sos fusion proteins confirm the formation of complexes containing p36 and the proline-rich COOH-terminal domain of Sos. The use of mutant GST-Grb2 proteins in which both SH3 domains have been mutationally inactivated shows that Grb2 binds to tyrosine phosphorylated p36 via its SH2 domain. In Jurkat cells phosphorylated p36 is localized exclusively in the particulate fraction. In addition, another SH2 domain-containing protein, p52Shc is tyrosine phosphorylated upon TCR.CD3 cross-linking and associates with a 150-kDa phosphotyrosine containing protein. Taken together these data suggest that activation of Ras in T cells via the TCR.CD3 complex might be controlled, at least in part, by mechanisms similar to those found in fibroblasts, involving in this case formation of a complex of Grb2, Sos, and a membrane-bound tyrosine phosphoprotein of molecular mass 36-kDa.