Activation of the Raf-1 kinase cascade by coumermycin-induced dimerization

M. A. Farrar, J. Alberola-Ila, R. M. Perlmutter

Research output: Contribution to journalArticlepeer-review

275 Scopus citations


The Raf-1 serine/threonine kinase is a key component of the MAP kinase cascade, regulating both proliferation and commitment to cell fate. Raf activation is stimulated following its translocation to the plasma membrane, a process that ordinarily requires interaction with the membrane-localized GTPase, Ras-GTP. To investigate the mechanisms underlying Raf activation, we have developed a coumermycin-induced chemical dimerization method. We find that dimerization is by itself sufficient, in the absence of any membrane components, both to activate a modified Raf protein and to stimulate the MAP kinase cascade appropriately. As Ras-GTP-induced membrane localization increases the effective intracellular Raf concentration, our results indicate that homotypic oligomerization may ordinarily act to promote Raf activation in vivo.

Original languageEnglish (US)
Pages (from-to)178-181
Number of pages4
Issue number6596
StatePublished - 1996


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