Epidermal growth factor (EGF) stimulates association and kinase activity of Raf-1 with the EGF receptor.
Raf-1 serine- and threonine-specific protein kinase is transiently activated in cells expressing the epidermal growth factor (EGF) receptor upon treatment with EGF. The stimulated EGF receptor coimmunoprecipitates with Raf-1 kinase and mediates protein kinase C-independent phosphorylation of Raf-1 on serine residues. Hyperphosphorylated Raf-1 has lower mobility on sodium dodecyl sulfate gels and has sixfold-increased activity in immunocomplex kinase assay with histone H1 or Raf-1 sequence-derived peptide as a substrate. Raf-1 activation requires kinase-active EGF receptor; a point mutant lacking tyrosine kinase activity in inactive in Raf-1 coupling and association. It is noteworthy that tyrosine phosphorylation of c-Raf-1 induced by EGF was not detected in these cells. These observations suggest that Raf-1 kinase may act as an important downstream effector of EGF signal transduction.
App
H
H
Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702.
Hazan
R
R
Zilberstein
A
A
Ullrich
A
A
Schlessinger
J
J
Rapp
U
U
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000936:Antigen-Antibody Complex / Q000032:analysis; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D007106:Immune Sera; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D014162:Transfection
D000596:Amino Acids; D000936:Antigen-Antibody Complex; D007106:Immune Sera; D011518:Proto-Oncogene Proteins; D004815:Epidermal Growth Factor; D011494:Protein Kinases; D066246:ErbB Receptors; D019908:Proto-Oncogene Proteins c-raf