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

Cell. 1997 Apr 4;89(1):73-82. doi: 10.1016/s0092-8674(00)80184-1.

Abstract

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-1 and 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.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cattle
  • Cell Differentiation / physiology
  • Cell Membrane / enzymology
  • Cyclic AMP / pharmacology*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • DNA-Binding Proteins*
  • Guanosine Triphosphate / metabolism
  • Neurons / cytology
  • Neurons / enzymology
  • PC12 Cells / cytology
  • PC12 Cells / drug effects
  • PC12 Cells / enzymology
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-raf
  • Protozoan Proteins / metabolism*
  • Rats
  • Transcription Factors / metabolism
  • ets-Domain Protein Elk-1

Substances

  • DNA-Binding Proteins
  • Elk1 protein, rat
  • Proto-Oncogene Proteins
  • Protozoan Proteins
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • rhoptry associated protein, Plasmodium
  • Guanosine Triphosphate
  • Cyclic AMP
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases