Issue 4, 2013

It takes two to tango – signalling by dimeric Raf kinases

Abstract

Raf kinases function downstream of Ras proteins to activate the MEK–ERK pathway which is deregulated in a large number of human cancers. Raf inhibitors are clinically highly effective for the treatment of cancer and melanoma in particular, but have unexpected side effects that include a paradoxical activation of the ERK pathway. These effects seem to be related to the heterodimerization of Raf-1 and B-Raf kinases. Here, we discuss the role of Raf dimerization as part of the physiological activation mechanism of Raf kinases, the mechanism of Raf dimerization induced by drugs, and the implications of dimerization for drug therapies targeting Raf kinases.

Graphical abstract: It takes two to tango – signalling by dimeric Raf kinases

Article information

Article type
Review Article
Submitted
27 Sep 2012
Accepted
11 Nov 2012
First published
13 Nov 2012

Mol. BioSyst., 2013,9, 551-558

It takes two to tango – signalling by dimeric Raf kinases

A. Baljuls, B. N. Kholodenko and W. Kolch, Mol. BioSyst., 2013, 9, 551 DOI: 10.1039/C2MB25393C

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