Fig 4.

Optimal p38 activation preferentially requires SOS1. (A to D) siRNA-driven knockdown of SOS1 in Jurkat T cells (A and C) or in human peripheral blood CD4⁺ T cells (B and D) results in a reduction of TCR-triggered p38 activation that is more pronounced than when RasGRP1 expression levels are reduced by siRNA-driven knockdown. (A and B) Partial reproduction of Fig. 2B and C in Roose et al. (20), and experimental details are described there. Mouse RasGRP1-specific siRNA duplex was used for off-target effect control in both experiments. Residual expression levels of SOS1 and RasGRP1 are represented as percentages of the control level. Representative of three independent experiments. (E and F) Impaired BCR-induced p38 activation in the absence of SOS. Wild-type and mutant DT40 cells were stimulated with a high dosage of M4 anti-BCR antibody for the indicated time. Percentages relative to the wild-type maximum response of pERK and phospho-p38 normalized to each total protein level are plotted in panel F. Data are means ± standard deviations (SD) from four independent experiments.