Requirement of Ras-GTP-Raf complexes for activation of Raf-1 by protein kinase C

Science. 1998 Apr 3;280(5360):109-12. doi: 10.1126/science.280.5360.109.

Abstract

Receptor tyrosine kinase-mediated activation of the Raf-1 protein kinase is coupled to the small guanosine triphosphate (GTP)-binding protein Ras. By contrast, protein kinase C (PKC)-mediated activation of Raf-1 is thought to be Ras independent. Nevertheless, stimulation of PKC in COS cells led to activation of Ras and formation of Ras-Raf-1 complexes containing active Raf-1. Raf-1 mutations that prevent its association with Ras blocked activation of Raf-1 by PKC. However, the activation of Raf-1 by PKC was not blocked by dominant negative Ras, indicating that PKC activates Ras by a mechanism distinct from that initiated by activation of receptor tyrosine kinases.

MeSH terms

  • Animals
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Chlorocebus aethiops
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Epidermal Growth Factor / pharmacology
  • Guanosine Triphosphate / metabolism*
  • Indoles / pharmacology
  • Mutation
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Proto-Oncogene Proteins c-raf / genetics
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Receptor, Muscarinic M1
  • Receptors, Muscarinic / metabolism
  • Signal Transduction
  • Tetradecanoylphorbol Acetate / pharmacology
  • ras Proteins / metabolism*

Substances

  • CHRM1 protein, human
  • Enzyme Inhibitors
  • Indoles
  • Receptor, Muscarinic M1
  • Receptors, Muscarinic
  • Epidermal Growth Factor
  • Guanosine Triphosphate
  • Proto-Oncogene Proteins c-raf
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • ras Proteins
  • Tetradecanoylphorbol Acetate
  • Ro 31-8220