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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References
Avruch, J., Zhang, X.-F. & Kyriakis, J. Trends Biochem. Sci. 19, 279–283 (1994).
Freed, E., Symons, M., McDonald, S. G., McCormick, F. & Ruggieri, R. Science 265, 1713–1715 (1994).
Luo, Z., Zhang, X.-F., Rapp, U. & Avruch, J. J. Biol. Chem. 270, 23681–23687 (1995).
Xiao, B. et al. Nature 376, 188–191 (1995).
Liu, D. et al. Nature 376, 191–194 (1995).
Liu, J. et al. Cell 66, 807–815 (1991).
Spencer, D. M., Wandless, T. J., Schreiber, S. L. & Crabtree, G. R. Science 262, 1019–1024 (1993).
Pruschy, M. N. et al. Curr. Biol. 1, 163–172 (1994).
Boguski, M. S. & McCormick, F. Nature 366, 643–654 (1993).
Zhang, X.-F. et al. Nature 364, 308–313 (1993).
Vojtek, A. B., Hollenberg, S. M. & Cooper, J. Cell 74, 205–214 (1993).
Chuang, E. et al. Mol. Cell. Biol. 14, 5318–5325 (1994).
Hu, C.-D. et al. J. Biol. Chem. 270, 30274–30277 (1995).
Kovacina, K. S. et al. J. Biol. Chem. 265, 12115–12118 (1990).
Dent, P., Jelinek, T., Morrison, D. K., Weber, M. J. & Sturgill, T. W. Science 268, 1902–1906 (1995).
Lemmon, M. A. & Schlessinger, J. Trends Biochem. Sci. 19, 459–463 (1994).
Johnson, L. N., Noble, M. E. M. & Owen, D. J. Cell 85, 149–158 (1996).
Yammamori, B. et al. J. Biol. Chem. 270, 11723–11726 (1995).
Okada, T., Masuda, T., Shinkai, M., Kariya, K.-I. & Kataoka, T. J. Biol. Chem. 271, 4671–4678 (1996).
Belshaw, P. J., Ho, S. N., Crabtree, G. R. & Schreiber, S. L. Proc. Natl Acad. Sci. USA 93, 4604–4607 (1996).
Field, J. et al. Mol. Cell. Biol. 8, 2159–2166 (1988).
Evan, G. I., Lewis, G. K., Ramsey, G. & Bishop, J. M. Mol. Cell. Biol. 5, 3610–3616 (1985).
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Luo, Z., Tzivion, G., Belshaw, P. et al. Oligomerization activates c-Raf-1 through a Ras-dependent mechanism. Nature 383, 181–185 (1996). https://doi.org/10.1038/383181a0
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DOI: https://doi.org/10.1038/383181a0
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