Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Leipziger Strasse 44, Magdeburg 39120, Germany.
EMBO Rep. 2012 Apr;13(4):386-91. doi: 10.1038/embor.2012.17.
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.
Sos 蛋白是 Ras 的普遍表达激活剂。淋巴细胞还表达另一种 Ras 激活剂 RasGRP1。Sos 和 RasGRP1 被认为在 T 细胞受体触发时协同控制 Ras 的完全激活。使用 RNA 干扰，我们评估了该机制是否在原代人 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，但不需要 Grb2/Sos。相反，Grb2/Sos—但不是 RasGRP1—是 IL2 介导的 Erk 激活所必需的。因此，RasGRP1 和 Grb2/Sos 是由不同刺激诱导的 Ras 激活信号的绝缘子，而不是 TCR 下游的合作分子。
