Abstract
In higher eukaryotes, the Ras and Raf-1 proto-oncoproteins transduce growth and differentiation signals initiated by tyrosine kinases. The Ras polypeptide and the amino-terminal regulatory domain of Raf-1(residues 1–257) are shown to interact, directly in vitro and in a yeast expression system. Raf-1(1-257) binds GTP-Ras in preference to GDP-Ras, and inhibits Ras-GAP activity. Mutations in and around the Ras effector domain impair Ras binding to Raf-1(1-257) and Ras transforming activity in parallel.
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References
Satoh, T., Nakafuku, T. & Kaziro, Y. J. biol. Chem. 267, 24149–24152 (1992).
Heidecker, G., Kolch, N., Morrison, D. K. & Rapp, U. R. Adv. Cancer Res. 58, 53–73 (1992).
Gibbs, J. B. & Marshall, M. D. Microbiol. Rev. 53, 171–185 (1989).
Pomerance, M., Schweighoffer, F., Tocque, B. & Pierre, M. J. biol. Chem. 267, 16155–16160 (1992).
Hattori, G. et al. J. biol. Chem. 267, 20346–20351.
Leevers, S. J. & Marshall, C. J. EMBO J. 11, 569–574 (1992).
Thomas, S. M. et al. Cell 68, 1031–1041 (1992).
Wood, K. W., Sarnecki, C., Roberts, T. M. & Blenis, J. Cell 68, 1041–1050 (1992).
Robbins, D. J. et al. Proc. natn. Acad. Sci. U.S.A. 89, 6924–6928 (1992).
Troppmair, J. et al. Oncogene 7, 1867–1873 (1992).
Shibuya, E. K. et al. Proc. natn. Acad. Sci. U.S.A. 89, 9831–9835 (1992).
Itoh, T. et al. J. biol. Chem. 268, 3025–3028 (1993).
Sturgill, T. W. et al. Nature 334, 715–717 (1988).
Barrett, C. B. & Maller, J. L. J. biol. Chem. 267, 4408–4415 (1992).
Grove, J. R. et al. Biochemistry (in the press).
Ahn, N. G. et al. J. biol. Chem. 266, 4220–4227 (1991).
Kosako, H. et al. EMBO J. 11, 2903–2908 (1992).
Gomez, N. & Cohen, P. Nature 351, 69–72 (1991).
Crews, C. M., Alessandrini, A. A. & Erikson, R. L. Science 258, 470–480 (1992).
Kyriakis, J. M. et al. Nature 358, 417–421 (1992).
Dent, P. et al. Science 257, 1404–1407 (1992).
Howe, L. R. et al. Cell 71, 335–342 (1992).
Tsuda, L. et al. Cell 72, 407–414 (1993).
Kolch, W., Heidecker, G., Lloyd, P. & Rapp, U. R. Nature 349, 426–428 (1991).
Rapp, U. R. et al. Cold Spring Harbor Symp. quant. Biol. 53, 173–181 (1988).
Huleihel, M. et al. Molec. cell. Biol. 6, 62655–62662 (1986).
Kovacina, K. D. et al. J. biol. Chem. 265, 12115–12118 (1990).
Kyriakis, J. M. et al. J. biol. Chem. (in the press).
Stanton, V. P. Jr et al. Molec. cell. Biol. 9, 636–643 (1989).
Heidecker, G. et al. Molec. cell. Biol. 10, 2503–2510 (1990).
Bruder, J. T., Heidecker, G. & Rapp, U. R. Genes Dev. 6, 545–556 (1992).
Hancock, J. F. et al. Cell 57, 1167–1177 (1989).
Page, M. J. et al. J. biol. Chem. 264, 19147–19156 (1989).
Marshall, M. S. et al. Molec. cell. Biol. 11, 3999–4004 (1991).
Durfee, T. et al. Genes Develop. 7, 555–569 (1993).
Chien, C. T., Bartel, P. L., Sternglanz, R. & Fields, S. Proc. natn. Acad. Sci. U.S.A. 88, 9578–9582 (1991).
Kitayama, H., Matsuzaki, T., Ikawa, Y. & Noda, M. Cell 56, 77–84 (1989).
Marshall, M. S. & Hettich, C. A. Oncogene 8, 425–431 (1993).
Pizon, V. et al. Oncogene 3, 201–204 (1988).
Pizon, V., Lerosey, L., Chardin, P. & Tavitian, A. Nucleic Acids Res. 16, 7719 (1988).
Campa, M. J. et al. Biochem. biophys. Res. Commun. 174, 1–5 (1991).
Kitayama, H., Mtsuzaki, T., Ikawa, Y. & Noda, M. Proc. natn. Acad. Sci. U.S.A. 87, 4284–4288 (1990).
Hata, P. et al. J. biol. Chem. 265, 7104–7110 (1990).
Frech, M. et al. Science 249, 169–171 (1990).
Quillam, L. A. et al. Molec. cell. Biol. 10, 2901–2908 (1990).
Mizuno, T. et al. Proc. natn. Acad. Sci. U.S.A. 88, 6442–6446 (1991).
Guan, K. L. & Dixon, J. E. Analyt. Biochem. 192, 262–267 (1991).
Ausubel, F. M. et al. in Current Protocols in Molecular Biology CH. 13 (Wiley Interscience, New York, 1990).
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Zhang, XF., Settleman, J., Kyriakis, J. et al. Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1. Nature 364, 308–313 (1993). https://doi.org/10.1038/364308a0
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DOI: https://doi.org/10.1038/364308a0
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