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

248 Scopus citations

Abstract

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
JournalNature
Volume383
Issue number6596
DOIs
StatePublished - 1996

Fingerprint

Dive into the research topics of 'Activation of the Raf-1 kinase cascade by coumermycin-induced dimerization'. Together they form a unique fingerprint.

Cite this