EGF receptor and PKCδ kinase activate DNA damage–induced pro-survival and pro-apoptotic signaling via biphasic activation of ERK and MSK1 kinases

Abstract

In both models, PKCδ inhibition preferentially suppressed late activation of ERK. We have shown previously that nuclear localization of PKCδ is necessary and sufficient for apoptosis. Here we identified a nuclear PKCδ→ERK→MSK1 signaling module that regulates apoptosis. We also show that expression of nuclear PKCδ activates ERK and MSK1, that ERK activation is required for MSK1 activation, and that both ERK and MSK1 activation are required for apoptosis. Our findings suggest that location-specific activation by distinct upstream regulators may enable distinct functional outputs from common signaling pathways.