cAMP activates MAP kinase and Elk-1 through a B-Raf- and Rap1-dependent pathway

Cyclic adenosine monophosphate (cAMP) has tissue-specific effects on growth, differentiation, and gene expression. We show here that cAMP can activate the transcription factor Elk-1and induce neuronal differentiation of PC12 cells via its activation of the MAP kinase cascade. These cell type-specific actions of cAMP require the expression of the serine/threonine kinase B-Raf and activation of the small G protein Rap1. Rap1, activated by mutation or by the cAMP-dependent protein kinase PKA, is a selective activator of B-Raf and an inhibitor of Raf-1. Therefore, in B-Raf-expressing cells, the activation of Rap1 provides a mechanism for tissue-specific regulation of cell growth and differentiation via MAP kinase.