REVIEW
Cell Research (1998)8:81-98
© 1998 SIBS, CAS All rights reserved 1001-0602/98
The RAF family: an expanding network of post-translational controls
and protein-protein interactions.
Yuryev A, Wennogle LP.
Novartis Pharmaceuticals Corporation, Summit, NJ 07901, USA. Lawrence.Wennogle@pharma.novartis.com
Protein kinase RAF is strategically located in the "Ras-MAP-kinase
signal transduction pathway", a principle system which transmits signals
from growth factor receptors to the nucleus, resulting in cell proliferation.
Growth factor responses are mediated in part by activation of Ras, which
in turn activates RAF to phosphorylate MEK, its downstream substrate. MEK
activates MAP-kinase to influence nuclear events. It is clear, however,
that a network of signals other than those carried by Ras plays a role in
RAF regulation. These orthogonal influences are mediated by: serine/threonine
kinases, tyrosine kinases, and protein-protein interactions. As a further
complication to the RAF network, three isoforms of RAF have been established
which have divergent N-terminal regulatory domains. Whereas these divergent
regulatory domains implicate isoform-specific functions, no clear evidence
or hypothesis for distinct functions for individual isoforms has been presented.
Recently, "isoform-specific protein interactions" have been identified
among numerous proteins interacting with RAF. These studies may serve to
delineate independent functions for RAF isoforms. |
