Multiple pathways for activation of MAP kinases.
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.
Mitra
G
G
Department of Molecular Biology, Cleveland Clinic Foundation, OH.
Weber
M
M
Stacey
D
D
D016475:3T3 Cells; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D005459:Fluorides / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D027384:Oncogene Proteins v-raf; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014170:Transformation, Genetic
D017607:Aluminum Compounds; D016895:Culture Media, Serum-Free; D015682:Retroviridae Proteins, Oncogenic; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D027384:Oncogene Proteins v-raf; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D013755:Tetradecanoylphorbol Acetate; D005459:Fluorides; C032311:aluminum fluoride