Association of pRas and pRaf-1 in a complex correlates with activation of a signal transduction pathway.
BACKGROUND
A key pathway for transduction of proliferative, developmental and oncogenic stimuli from receptors at the cell surface to transcription factors located in the nucleus involves the activation of pRas and pRaf-1. Recent publications have described a physical interaction between pRas and pRaf-1, either as ectopic proteins in yeast or as recombinant proteins added to cellular extracts. Until now, however, physical complexes that include pRas and pRaf-1 have not been identified as native structures in mammalian cells.


RESULTS
We have directly identified a pRas-pRaf-1 complex in extracts of mammalian cells. Formation of the complex is augmented in neoplastically transformed cells expressing constitutively activated pRas. Moreover, the complexes form in concert with the activation of pRas during intracellular signalling through the T-cell receptor in T-leukemia cells.


CONCLUSIONS
We propose that, pRas signals to pRaf-1 in vivo by means of a direct physical interaction that results in activation of the pRaf-1 protein kinase.
Finney
R E
RE
The George Williams Hooper Foundation, University of California, Box 0552, San Francisco, California 94143, USA.
Robbins
S M
SM
Bishop
J M
JM