Differential regulation of Raf isozymes by growth versus differentiation inducing factors in PC12 pheochromocytoma cells

FEBS Lett. 1996 May 6;385(3):131-7. doi: 10.1016/0014-5793(96)00363-8.


PC12 pheochromocytoma cells possess four known MEK activators: A-, B-, c-Raf-1 and MEKK. In order to examine whether differentiation factors or growth factors have a Raf isozyme preference for activation of the mitogenic cytoplasmic Raf-MEK-MAPK protein kinase cascade, the activation kinetics of these enzymes in response to epidermal growth factor (EGF) and nerve growth factor (NGF) were compared. An initial activation of all three Raf kinases was noticed, but only A- and B-Raf showed sustained activation by NGF, which was not seen after EGF treatment. Furthermore, expression of oncogenic versions of all three Raf kinases as well, as a potentially Raf-independent MEK activator, v-Mos, leads to activation of MAPK and to differentiation of PC12 cells. These data suggest a differential regulation of Raf kinases and that probably no alternative Raf substrates are involved in differentiation processes of PC12 cells.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Differentiation
  • Cell Division
  • Enzyme Activation
  • Epidermal Growth Factor / pharmacology*
  • Immunoblotting
  • Isoenzymes / metabolism
  • Kinetics
  • Mitogen-Activated Protein Kinase Kinases
  • Nerve Growth Factors / pharmacology*
  • Neurites / ultrastructure
  • Neurons / cytology
  • Oncogene Proteins v-mos / genetics
  • Oncogene Proteins v-mos / pharmacology
  • PC12 Cells
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-raf
  • Rats
  • Transfection


  • Isoenzymes
  • Nerve Growth Factors
  • Oncogene Proteins v-mos
  • Proto-Oncogene Proteins
  • Epidermal Growth Factor
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases