Fig. 10. Effect of PD169316 on SP600125-induced sensitization of Fas-mediated apoptosis in Jurkat cells lacking p38, p38ß and JNK1/2. (A) Fas-mediated apoptosis was sensitized by PD169316 but inhibited by SP600125 in si-38 cells but only by SP600125 in si-p38ß cells, SP600125, but not PD169316 exerted the sensitizing effect. Both inhibitors (SP600125 > PD169316) potentiated Fas-mediated apoptosis in si-C cells. Fas-mediated apoptosis in si-JNK1/2 cells was comparable to that induced by SP600126 in si-C cells and was inhibited by PD169316. (B) The potentiating effect of SP600125 on the reduction in _m in response to Fas-activation was abrogated in both si-p38 cells and si-p38ß cells, but not in si-C cells. The reduction in _m in Fas-activated si-JNK1/2 cells was attenuated by. PD169316. (C,D,E) Fas-mediated activation of the three caspases in si-p38 cells was observed in presence, but not in absence of PD169316 and/or SP600125. Caspases 8 and 3 were activated to a greater extent in si-p38ß and si-JNK1/2 cells. Caspase-9 activation was lesser in si-p38ß cells and greater in si-JNK1/2 cells than that seen in si-C cells, and was suppressed by PD169316. The sensitizing effect of SP600125 on caspase-9 was markedly lower in si-p38 and si-p38ß cells than in si-C cells.