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

Laura L. Dugan, Joanna S. Kim, Yujing Zhang, Robert D. Bart, Yuling Sun, David M. Holtzman, David H. Gutmann

Research output: Contribution to journalArticle

190 Scopus citations

Abstract

Mitogen-activated protein kinase (MAPK) activation provides cell type- specific signals important for cellular differentiation, proliferation, and survival. 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 central nervous system-derived neurons, but not astrocytes, express B-raf. In neurons, cAMP activated MAPK in a Rap1/B-raf-dependent manner, while in astrocytes, cAMP decreased MAPK activity. Inhibition of MAPK in neurons decreased neuronal growth factor-mediated survival, and activation of MAPK by cAMP analogues rescued neurons from death. Furthermore, constitutive expression of B-raf in astrocytoma cells increased MAPK activation, as seen in neurons, and enhanced proliferation. These data provide the first experimental evidence that B-raf is the molecular switch which dominantly permits differential cAMP-dependent regulation of MAPK in neurons versus astrocytes, with important implications for both survival and proliferation.

Original languageEnglish
Pages (from-to)25842-25848
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number36
DOIs
StatePublished - Sep 3 1999

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