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

Nature volume 383, pages 178181 (12 September 1996) | Download Citation

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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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Author information

Affiliations

  1. Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA

    • José Alberola-lla
    •  & Roger M. Perlmutter
  2. Department of Immunology, University of Washington, Seattle, Washington 98195, USA

    • Michael A. Farrar
    • , José Alberola-lla
    •  & Roger M. Perlmutter
  3. Department of Biochemistry and Medicine (Medical Genetics), University of Washington, Seattle, Washington 98195, USA

    • Roger M. Perlmutter

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https://doi.org/10.1038/383178a0

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