TCR‐mediated Erk activation does not depend on Sos and Grb2 in peripheral human T cells
TCR‐mediated Erk activation does not depend on Sos and Grb2 in peripheral human T cells
复制标题
DOI：
10.1038/embor.2012.17
复制
发表时间：
2012-04
期刊：
影响因子：
7.7
通讯作者：
Nicole Warnecke;M. Poltorak;B. Kowtharapu;Boerge Arndt;J. Stone;B. Schraven;L. Simeoni
中科院分区：
文献类型：
--
作者：
Nicole Warnecke;M. Poltorak;B. Kowtharapu;Boerge Arndt;J. Stone;B. Schraven;L. Simeoni
SOS蛋白是广泛表达的RAS激活剂。淋巴样细胞也表达另一种RAS激活剂RASGRP1。SOS和RASGRP1被认为在T细胞受体触发时协同控制全部RAS的激活。利用RNA干扰，我们评估了这种机制是否在原代人类T细胞中起作用。我们发现，T细胞抗原受体(TCR)介导的ERK激活需要RASGRP1，而不需要Grb2/SOS。相反，IL2介导的ERK激活需要Grb2/SOS而不是RASGRP1。因此，RASGRP1和Grb2/SOS是导致不同刺激诱导RAS激活的信号的绝缘体，而不是在TCR下游协同作用。
Sos proteins are ubiquitously expressed activators of Ras. Lymphoid cells also express RasGRP1, another Ras activator. Sos and RasGRP1 are thought to cooperatively control full Ras activation upon T‐cell receptor triggering. Using RNA interference, we evaluated whether this mechanism operates in primary human T cells. We found that T‐cell antigen receptor (TCR)‐mediated Erk activation requires RasGRP1, but not Grb2/Sos. Conversely, Grb2/Sos—but not RasGRP1—are required for IL2‐mediated Erk activation. Thus, RasGRP1 and Grb2/Sos are insulators of signals that lead to Ras activation induced by different stimuli, rather than cooperating downstream of the TCR.