Mitogen-activated protein kinase transcription factor signal-dependent

In contrast, several lines of evidence suggest that the activation of the Ras-Raf-ERKl/2 pathway may oppose JNK-mediated effects with respect to mitochondria-dependent apoptosis (Fig. 4). ERKl/2 can phosphorylate and activate mitogen-and stress-activated kinase 1 (MSKl) and pp90 ribosomal S6 kinase (RSK) [83,84]. RSK can phosphorylate BAD, thereby inhibiting its proapoptotic effects [83]. Furthermore, both RSK and MSKl are potent activators of cyclic adenosine monophosphate (cAMP) element binding protein (CREB), a transcription factor for Blc-2, and therefore important for cell survival [84]. The upregulation or overexpression of Bcl-2 has been reported to be associated with the inactivation of JNK [75,85]. Thus, ERKl/2 activation could ultimately lead to JNK inactivation. Finally, the activation of c-Ras has been shown to result in a suppression of Bax expression, via a mechanism that involved activation of both the ERKl/2 signaling cascade and the phosphatidylinositol-3 -kinase (PI-3)/Akt pathway [80]. 

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