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Review
. 2015 May;16(5):281-98.
doi: 10.1038/nrm3979.

Regulation of RAF protein kinases in ERK signalling

Hugo Lavoie  1 , Marc Therrien  2
Affiliations
Review

Regulation of RAF protein kinases in ERK signalling

Hugo Lavoie et al. Nat Rev Mol Cell Biol. 2015 May.

Abstract

RAF family kinases were among the first oncoproteins to be described more than 30 years ago. They primarily act as signalling relays downstream of RAS, and their close ties to cancer have fuelled a large number of studies. However, we still lack a systems-level understanding of their regulation and mode of action. The recent discovery that the catalytic activity of RAF depends on an allosteric mechanism driven by kinase domain dimerization is providing a vital new piece of information towards a comprehensive model of RAF function. The fact that current RAF inhibitors unexpectedly induce ERK signalling by stimulating RAF dimerization also calls for a deeper structural characterization of this family of kinases.

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