Epidermal growth factor stimulates phosphorylation of RAF-1 independently of receptor autophosphorylation and internalization

M. Baccarini, G. N. Gill, E. R. Stanley

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Phosphorylation of the RAF-1 protooncogene product and activation of its associated serine/threonine kinase are common features of the response of cells to peptide growth factors. We have used wild-type and mutant epidermal growth factor (EGF) receptors to investigate mechanisms of RAF-1 phosphorylation. In vivo EGF treatment rapidly stimulated phosphorylation of RAF-1 exclusively on serine residues. Stimulation of RAF-1 phosphorylation occurred at 37 °C but not at 4 °C and persisted after dissociation of EGF from its receptor. EGF-induced RAF-1 serine phosphorylation required the intrinsic tyrosine kinase activity of the EGF receptor but was independent of EGF receptor self-phosphorylation and of ligand-induced receptor internalization. Down-regulation of protein kinase C did not affect the EGF-induced increase in RAF-1 phosphorylation. These data suggest that the activated tyrosine kinase activity of the EGF receptor enhances serine phosphorylation of RAF-1 via an intermediary molecule(s).

Original languageEnglish (US)
Pages (from-to)10941-10945
Number of pages5
JournalJournal of Biological Chemistry
Issue number17
StatePublished - Sep 6 1991


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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