Ras controls coupling of growth factor receptors and protein kinase C in the membrane to Raf-1 and B-Raf protein serine kinases in the cytosol

Jakob Troppmair, Joseph T. Bruder, Harald App, Hong Cai, Lauren Liptak, J. Szeberényi, Geoffrey M. Cooper, Ulf R. Rapp

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Abstract

A dominant negative mutant of Ras, M17 Ras, was used to study the role of Ras in receptor coupling of Raf-1 and B-Raf protein serine/threonine kinases (PSKs). We found that mutant Ras blocks serum- and 12-O-tetradecanoyl phorbol 13-acetate-induced activation of Raf-1 kinase in NIH3T3 cells and Raf-1 as well as B-Raf PSK stimulation by nerve growth factor (NGF) in PC12 pheochromocytoma cells. Mitogen stimulation of Raf kinase was measured by determination of Raf hyperphosphorylation and activity towards exogenous substrates and both of these events were inhibited in cells expressing M17 Ras. In contrast, tyrosine phosphorylation of a direct substrate of activated tyrosine kinase receptors, phospholipase C-γ1 (PLC-γ1), was unaffected. These data indicate that tyrosine phosphorylation of PLC-γ1 is not sufficient for growth induction in NIH3T3 cells and that Ras mediates signal transfer from activated membrane receptors to Raf kinases in the cytosol. As activated Raf induced differentiation in PC12 cells expressing M17 Ras we conclude that Raf kinase activation may be sufficient to account for this aspect of NGF function.

Original languageEnglish
Pages (from-to)1867-1873
Number of pages7
JournalOncogene
Volume7
Issue number9
Publication statusPublished - Sep 1992

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Proto-Oncogene Proteins B-raf
raf Kinases
Growth Factor Receptors
Protein-Serine-Threonine Kinases
Cytosol
Protein Kinase C
PC12 Cells
Type C Phospholipases
Nerve Growth Factor
Membranes
Tyrosine
Proto-Oncogene Proteins c-raf
Phosphorylation
Receptor Protein-Tyrosine Kinases
Pheochromocytoma
Tetradecanoylphorbol Acetate
Mitogens
Growth
Serum

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Ras controls coupling of growth factor receptors and protein kinase C in the membrane to Raf-1 and B-Raf protein serine kinases in the cytosol. / Troppmair, Jakob; Bruder, Joseph T.; App, Harald; Cai, Hong; Liptak, Lauren; Szeberényi, J.; Cooper, Geoffrey M.; Rapp, Ulf R.

In: Oncogene, Vol. 7, No. 9, 09.1992, p. 1867-1873.

Research output: Contribution to journalArticle

Troppmair, J, Bruder, JT, App, H, Cai, H, Liptak, L, Szeberényi, J, Cooper, GM & Rapp, UR 1992, 'Ras controls coupling of growth factor receptors and protein kinase C in the membrane to Raf-1 and B-Raf protein serine kinases in the cytosol', Oncogene, vol. 7, no. 9, pp. 1867-1873.
Troppmair, Jakob ; Bruder, Joseph T. ; App, Harald ; Cai, Hong ; Liptak, Lauren ; Szeberényi, J. ; Cooper, Geoffrey M. ; Rapp, Ulf R. / Ras controls coupling of growth factor receptors and protein kinase C in the membrane to Raf-1 and B-Raf protein serine kinases in the cytosol. In: Oncogene. 1992 ; Vol. 7, No. 9. pp. 1867-1873.
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AU - Cai, Hong

AU - Liptak, Lauren

AU - Szeberényi, J.

AU - Cooper, Geoffrey M.

AU - Rapp, Ulf R.

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