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 Citations (Scopus)

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
StatePublished - Feb 1991
Externally publishedYes

Fingerprint

Proto-Oncogene Proteins c-raf
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Phosphorylation
Protein-Serine-Threonine Kinases
Sodium Dodecyl Sulfate
Histones
Protein-Tyrosine Kinases
Serine
Protein Kinase C
Tyrosine
Signal Transduction
Phosphotransferases
Gels
Peptides

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

App, H., Hazan, R., Zilberstein, A., Ullrich, A., Schlessinger, J., & Rapp, U. (1991). Epidermal Growth Factor (EGF) Stimulates Association and Kinase Activity of Raf-1 with the EGF Receptor. Molecular and Cellular Biology, 11(2), 913-919.

Epidermal Growth Factor (EGF) Stimulates Association and Kinase Activity of Raf-1 with the EGF Receptor. / App, Harald; Hazan, Rachel; Zilberstein, Asher; Ullrich, Axel; Schlessinger, Joseph; Rapp, Ulf.

In: Molecular and Cellular Biology, Vol. 11, No. 2, 02.1991, p. 913-919.

Research output: Contribution to journalArticle

App, H, Hazan, R, Zilberstein, A, Ullrich, A, Schlessinger, J & Rapp, U 1991, 'Epidermal Growth Factor (EGF) Stimulates Association and Kinase Activity of Raf-1 with the EGF Receptor', Molecular and Cellular Biology, vol. 11, no. 2, pp. 913-919.
App, Harald ; Hazan, Rachel ; Zilberstein, Asher ; Ullrich, Axel ; Schlessinger, Joseph ; Rapp, Ulf. / Epidermal Growth Factor (EGF) Stimulates Association and Kinase Activity of Raf-1 with the EGF Receptor. In: Molecular and Cellular Biology. 1991 ; Vol. 11, No. 2. pp. 913-919.
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