CAMP ACTIVATES MAP KINASE AND ELK-1 THROUGH A B-RAF-DEPENDENT AND RAP1-DEPENDENT PATHWAY

Cyclic adenosine monophosphate (cAMP) has tissue-specific effects on g rowth, differentiation, and gene expression. We show here that cAMP ca n activate the transcription factor Elk-1and induce neuronal different iation of PC12 cells via its activation of the MAP kinase cascade. The se cell type-specific actions of cAMP require the expression of the se rine/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. Ther efore, in B-Raf-expressing cells, the activation of Rap1 provides a me chanism for tissue-specific regulation of cell growth and differentiat ion via MAP kinase.