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TCR‐mediated Erk activation does not depend on Sos and Grb2 in peripheral human T cells
Author(s) -
Warnecke Nicole,
Poltorak Mateusz,
Kowtharapu Bhavani S,
Arndt Boerge,
Stone James C,
Schraven Burkhart,
Simeoni Luca
Publication year - 2012
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2012.17
Subject(s) - t cell receptor , mapk/erk pathway , grb2 , microbiology and biotechnology , activator (genetics) , biology , t cell , guanine nucleotide exchange factor , signal transduction , receptor , genetics , signal transducing adaptor protein , immune system
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.