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Cell Mol Life Sci. 2011 Feb;68(4):553-65. doi: 10.1007/s00018-010-0520-6. Epub 2010 Sep 6.

Mechanistic principles of RAF kinase signaling.

Author information

1
Laboratory of Intracellular Signaling, Département de pathologie et de biologie cellulaire, Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montreal, QC, H3C 3J7, Canada.

Abstract

The RAF family of kinases are key components acting downstream of receptor tyrosine kinases and cells employ several distinct mechanisms to strictly control their activity. RAF transitions from an inactive state, where the N-terminal regulatory region binds intramolecularly to the C-terminal kinase domain, to an open state capable of executing the phosphoryl transfer reaction. This transition involves changes both within and between the protein domains in RAF. Many different proteins regulate the transition between inactive and active states of RAF, including RAS and KSR, which are arguably the two most prominent regulators of RAF function. Recent developments have added several new twists to our understanding of RAF regulation. Among others, dimerization of the RAF kinase domain is emerging as a crucial step in the RAF activation process. The multitude of regulatory protein-protein interactions involving RAF remains a largely untapped area for therapeutic applications.

PMID:
20820846
DOI:
10.1007/s00018-010-0520-6
[Indexed for MEDLINE]

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