Abstract
THE Raf-1 serine/threonine kinase is a key component of the MAP kinase cascade1–3, regulating both proliferation and commitment to cell fate4,5. Raf activation is stimulated following its transloca-tion to the plasma membrane, a process that ordinarily requires interaction with the membrane-localized GTPase, Ras-GXP6–10. 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.
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Farrar, M., Alberola-lla, J. & Perlmutter, R. Activation of the Raf-1 kinase cascade by coumermycin-induced dimerization. Nature 383, 178–181 (1996). https://doi.org/10.1038/383178a0
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DOI: https://doi.org/10.1038/383178a0
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