Epidermal Growth Factor (EGF) Stimulates Association and Kinase Activity of Raf-1 with the EGF Receptor

Harald App, Rachel Hazan, Asher Zilberstein, Axel Ullrich, Joseph Schlessinger, Ulf Rapp

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

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 assays with histone H1 or a Raf-1 sequence-derived peptide as a substrate. Raf-1 activation requires kinase-active EGF receptor; a point mutant lacking tyrosine kinase activity is 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.

Original languageEnglish (US)
Pages (from-to)913-919
Number of pages7
JournalMolecular and cellular biology
Volume11
Issue number2
DOIs
StatePublished - Feb 1991
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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