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Oligomerization activates c-Raf-1 through a Ras-dependent mechanism

Nature volume 383, pages 181185 (12 September 1996) | Download Citation

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Abstract

THE c-Raf-1 proto-oncoprotein is a Ras-GTP-regulated protein kinase1 that associates in situ with 14-3-3 proteins2,3, which are naturally dimeric4,5. In COS cells, recombinant Raf is found in oligomeric assemblies. To examine whether induced oligomeriza-tion can alter Raf kinase activity, sequences encoding the FK506-binding protein FKBP12 were fused to the amino terminus of c-Raf-1, introducing a binding site for FK506. Oligomerization of recombinant FKBP-Raf in situ, induced by the addition of the dimeric FK506 derivative FK1012A, activated Raf kinase activity at least half as well as epidermal growth factor (EGF). As with EGF, activation of FKBP-Raf by FK1012A is entirely Ras-GTP dependent. Thus Oligomerization of Raf per se promotes Raf activation through a Ras-dependent mechanism.

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Affiliations

  1. Diabetes Unit and Medical Services, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02129, USA

    • Zhijun Luo
    • , Guri Tzivion
    • , Demetrios Vavvas
    •  & Joseph Avruch
  2. Howard Hughes Medical Institute, and Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA

    • Peter J. Belshaw
  3. Department of Medicine, Division of Hematology and Oncology, Department of Biochemistry and Molecular Biology, and Walther Oncology Center, Indiana University, Indianapolis, Indiana 46202, USA

    • Mark Marshall

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https://doi.org/10.1038/383181a0

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