S os1 regulates sustained TCR‐mediated E rk activation

M Poltorak, I Meinert, JC Stone… - European journal of …, 2014 - Wiley Online Library
M Poltorak, I Meinert, JC Stone, B Schraven, L Simeoni
European journal of immunology, 2014Wiley Online Library
The duration and/or the magnitude of R as‐E rk activation are known to be crucial for cell‐
fate decisions. In T cells, sustained E rk activation correlates with differentiation/proliferation,
whereas transient E rk activation parallels with unresponsiveness/apoptosis. The
mechanism by which S on of sevenless (S os) proteins and R as guanyl‐releasing protein 1
(R as GRP 1) contribute to dynamics of E rk activation in mature T cells is not yet known.
Here, we have assessed this issue using stimuli inducing either transient or sustained TCR …
The duration and/or the magnitude of Ras‐Erk activation are known to be crucial for cell‐fate decisions. In T cells, sustained Erk activation correlates with differentiation/proliferation, whereas transient Erk activation parallels with unresponsiveness/apoptosis. The mechanism by which Son of sevenless (Sos) proteins and Ras guanyl‐releasing protein 1 (RasGRP1) contribute to dynamics of Erk activation in mature T cells is not yet known. Here, we have assessed this issue using stimuli inducing either transient or sustained TCR signaling and RNA interference mediated suppression of Sos1, Sos2, and RasGRP1 expression in primary human T cells. We found that transient Erk activation depends on RasGRP1 but not on Sos. Conversely, sustained Erk signaling and T‐cell activation depend on both Sos1 and RasGRP1. In summary, our data show for the first time that the two guanine nucleotide exchange factors expressed in T cells are differentially involved in the regulation of the duration of Erk phosphorylation and T‐cell activation.
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