Multiple pathways for activation of MAP kinases

Cell Mol Biol Res. 1993;39(5):517-23.


p42/Mitogen activated protein kinase (MAPK) and MAP Kinase Kinase (MAPKK) activities are constitutively elevated in v-raf transformed NIH3T3 cells, which correlates with increased tyrosine phosphorylation of p42mapk protein. These activities can be further enhanced to a moderate extent by treatment of raf-transformed cells with either serum, tetradecanoyl phorbol acetate (TPA), or aluminium fluoride. A similar activation of MAPK is observed in a cell line (M17raf) coexpressing a dominant inhibitory ras mutant (N-17 ras) along with v-raf. However, in this cell line, both the serum and TPA stimulated response of MAPK activity is reduced compared to similarly treated raf-transformed cells, while aluminium fluoride is equally potent in all the cell lines tested. These studies indicate that in addition to c-Raf-1, serine/threonine kinase, which is an upstream activator of MAPK, other c-ras dependent as well as c-ras independent pathways also can contribute to MAPK activation.

MeSH terms

  • 3T3 Cells
  • Aluminum Compounds / pharmacology
  • Animals
  • Culture Media, Serum-Free
  • Enzyme Activation
  • Fluorides / pharmacology
  • Gene Expression Regulation, Enzymologic
  • Mice
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase Kinases
  • Oncogene Proteins v-raf
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism*
  • Retroviridae Proteins, Oncogenic / genetics*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transformation, Genetic


  • Aluminum Compounds
  • Culture Media, Serum-Free
  • Retroviridae Proteins, Oncogenic
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Oncogene Proteins v-raf
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase Kinases
  • Tetradecanoylphorbol Acetate
  • Fluorides
  • aluminum fluoride