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TCR-mediated Erk activation does not depend on Sos and Grb2 in peripheral human T cells.


ABSTRACT: 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.

SUBMITTER: Warnecke N 

PROVIDER: S-EPMC3321150 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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TCR-mediated Erk activation does not depend on Sos and Grb2 in peripheral human T cells.

Warnecke Nicole N   Poltorak Mateusz M   Kowtharapu Bhavani S BS   Arndt Boerge B   Stone James C JC   Schraven Burkhart B   Simeoni Luca L  

EMBO reports 20120401 4


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 activ  ...[more]

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