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

J Biol Chem. 1999 Sep 3;274(36):25842-8. doi: 10.1074/jbc.274.36.25842.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cells, Cultured
  • Cyclic AMP / metabolism*
  • GTP-Binding Proteins / metabolism
  • Mice
  • Neurons / metabolism*
  • Organ Specificity
  • Proto-Oncogene Proteins c-raf / metabolism
  • Signal Transduction*
  • rap GTP-Binding Proteins


  • Cyclic AMP
  • Proto-Oncogene Proteins c-raf
  • Calcium-Calmodulin-Dependent Protein Kinases
  • GTP-Binding Proteins
  • rap GTP-Binding Proteins