A dimerization-dependent mechanism drives RAF catalytic activation

Thanashan Rajakulendran, Malha Sahmi, Martin Lefrançois, Frank Sicheri () and Marc Therrien ()
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Thanashan Rajakulendran: Centre for Systems Biology, Samuel Lunenfeld Research Institute, Toronto, Ontario M5G 1X5, Canada
Malha Sahmi: Institute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling,
Martin Lefrançois: Institute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling,
Frank Sicheri: Centre for Systems Biology, Samuel Lunenfeld Research Institute, Toronto, Ontario M5G 1X5, Canada
Marc Therrien: Institute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling,

Nature, 2009, vol. 461, issue 7263, 542-545

Abstract: The raf oncogene: dimerization drives RAF kinase Activation of the kinase RAF is triggered by growth factors binding to receptor tyrosine kinases, and raf is the most frequently mutated oncogene within the kinase superfamily. Here, the activation mechanism of RAF is shown to involve a dimeric conformation of its kinase domain. Dimerization is relevant for the action of the RAF activator KSR and certain oncogenic mutations. The work resolves a long-standing conundrum about the precise mechanism of RAF catalytic activation and offers new possibilities for future therapeutic development.

Date: 2009
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DOI: 10.1038/nature08314

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