Requirement of Ras-GTP-Raf Complexes for Activation of Raf-1 by Protein Kinase C
Richard Marais,
Yvonne Light,
Clive Mason,
Hugh Paterson,
Michael F. Olson,
Christopher J. Marshall
*
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.
CRC Centre for Cell and Molecular Biology, Institute of Cancer
Research, 237 Fulham Road, London SW3 6JB, UK.
*
To whom correspondence should be addressed. E-mail:
chrism{at}icr.ac.uk
