THE CYCLIC ADENOSINE MONOPHOSPHATE-DEPENDENT PROTEIN-KINASE (PKA) IS REQUIRED FOR THE SUSTAINED ACTIVATION OF MITOGEN-ACTIVATED KINASES ANDGENE-EXPRESSION BY NERVE GROWTH-FACTOR

Induction of neuronal differentiation of the rat pheochromocytoma cell line, PC12 cells, by nerve growth factor (NGF) requires activation of the mitogen-activated protein (MAP) kinase or extracellular signal-re gulated kinase (ERK). cAMP-dependent protein kinase (protein kinase A (PKA)) also call induce differentiation of these cells. Like NGF, the ability of PKA. to differentiate PC12 cells is associated with a susta ined activation of ERKs, Here we show that maximal sustained activatio n of ERK1 by NGF requires PKA, Inhibitors of PKA partially blocked act ivation of ERK1 by NGF but had no effect on activation of ERK1 by EGF. Inhibition of PRA also reduced the ability of NGF and cAMP, but not E GF, to activate the transcription factor Elk-1, reduced the induction of both immediate early and late genes after NGF treatment, and blocke d the nuclear translocation of ERK1 induced by NGF. We propose that PK A is an important contributor to the activation of ERK1 by NGF and is required for maximal induction of gene expression by NGF.