Differential effects of cAMP in neurons and astrocytes - Role of B-raf

Mitogen-activated protein kinase (MAPK) activation provides cell type-speci fic signals important for cellular differentiation, proliferation, and surv ival. Cyclic AMP (cAMP) has divergent effects on MAPK activity depending on whether signaling is through Ras/Raf-1 or Rap1/B-raf. We found that centra l nervous system-derived neurons, but not astrocytes, express B-raf. In neu rons, cAMP activated MAPK in a Rap1/B-raf-dependent manner, while in astroc ytes, cAMP decreased MAPK activity. Inhibition of MAPK in neurons decreased neuronal growth factor-mediated survival, and activation of MAPK by cAMP a nalogues rescued neurons from death. Furthermore, constitutive expression o f B-raf in astrocytoma cells increased MAPK activation, as seen in neurons, and enhanced proliferation. These data provide the first experimental evid ence that B-raf is the molecular switch which dominantly permits differenti al cAMP-dependent regulation of MAPK in neurons versus astrocytes, with imp ortant implications for both survival and proliferation.