Regulation of RAF protein kinases in ERK signalling

H Lavoie, M Therrien - Nature reviews Molecular cell biology, 2015 - nature.com
H Lavoie, M Therrien
Nature reviews Molecular cell biology, 2015nature.com
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 …
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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