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

Manuela Baccarini, Gordon N. Gill, E. Richard Stanley

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 ° 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
Volume266
Issue number17
StatePublished - 1991

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Phosphorylation
Epidermal Growth Factor
Epidermal Growth Factor Receptor
Serine
Protein-Tyrosine Kinases
Protein-Serine-Threonine Kinases
Protein Kinase C
Intercellular Signaling Peptides and Proteins
Down-Regulation
Chemical activation
Ligands
Peptides
Molecules

ASJC Scopus subject areas

  • Biochemistry

Cite this

Epidermal growth factor stimulates phosphorylation of RAF-1 independently of receptor autophosphorylation and internalization. / Baccarini, Manuela; Gill, Gordon N.; Richard Stanley, E.

In: Journal of Biological Chemistry, Vol. 266, No. 17, 1991, p. 10941-10945.

Research output: Contribution to journalArticle

Baccarini, Manuela ; Gill, Gordon N. ; Richard Stanley, E. / Epidermal growth factor stimulates phosphorylation of RAF-1 independently of receptor autophosphorylation and internalization. In: Journal of Biological Chemistry. 1991 ; Vol. 266, No. 17. pp. 10941-10945.
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