Requirement of Ras-GTP-Raf complexes for activation of Raf-1 by protein kinase C.
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.
Marais
R
R
CRC Centre for Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
Light
Y
Y
Mason
C
C
Paterson
H
H
Olson
M F
MF
Marshall
C J
CJ
D000818:Animals; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D009154:Mutation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism*; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018631:ras Proteins / Q000378:metabolism*
C086088:CHRM1 protein, human; D004791:Enzyme Inhibitors; D007211:Indoles; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D004815:Epidermal Growth Factor; D006160:Guanosine Triphosphate; D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018631:ras Proteins; D013755:Tetradecanoylphorbol Acetate; C064758:Ro 31-8220