ras Oncogenes pp 281-285 | Cite as

Identification of a Protein Interacting with ras-p21- by Chemical Cross-Linking

  • Jean de Gunzburg
  • Rebecca Riehl
  • Robert A. Weinberg

Abstract

There is accumulating evidence showing that ras oncogenes (Ha-ras, K-ras and N-ras) are involved in the processes of oncogenesis and cellular transformation1 . These genes encode highly homologous proteins of molecular weight 21 ,000 (p21) that are found in all mammalian tissues and are very conserved throughout evolution. ras-p21s are bound to the inner surface of the plasma membrane ; they bind GTP and GDP, and exhibit an intrinsic GTPase activity. A cytoplasmic protein of MW 110–120,000 has recently been identified by its capacity to enhance 100–500 fold the GTPase activity of ras-p21s (GAP) 2 ; it has been shown to interact with a domain of p21s necessary for their biological activity (amino acids 30–42 called “effector domain”) and may therefore constitute an effector of their physiological action3–6 . Point mutations resulting in the change of amino acids 12, 13, 59 or 61 have been shown to “activate” the oncogenic potential of ras oncogenes leading to cellular transformation. The GTPase activity of such mutant proteins is no longer activated by GAP, blocking them in a GTP-bound state that is thought to be the active form of p21s.

Keywords

GTPase Activity Intrinsic GTPase Activity Putative Effector Polyclonal Rabbit Serum Antiphosphotyrosine Antibody 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Barbacid, M. Ann. Rev. Biochem. 56, 779–827 (1987).PubMedCrossRefGoogle Scholar
  2. 2.
    Trahey, M. & McCormick, F. Science 238, 542–545 (1987).PubMedCrossRefGoogle Scholar
  3. 3.
    Adari, H., Lowy, D.R., Willumsen, B.M., Der, C.J. & Mc Cormick, F. Science, 240, 518–521 (1988).PubMedCrossRefGoogle Scholar
  4. 4.
    Calès, C., Hancock, J.F., Marshall, C.J. & Hall, A. Nature 332, 548–551.Google Scholar
  5. 5.
    Gibbs, J.B., Schaber, M.D., Allard, W.J., SigallI, S. & Scolnick, E.M. Proc. Natl. Acad. Sci. USA 85, 5026–5030 (1988).PubMedCrossRefGoogle Scholar
  6. 6.
    Vogel, U.S., Dixon, R.A.F., Schaber, M.D., Dielhl, R.E., Marshall, M.S., Scolnick, E.M., Sigal, I .S. & Gibbs, J.B. Nature 303, 90–93 (1988).CrossRefGoogle Scholar
  7. 7.
    Gilman, A.G. Ann. Rev. Biochem, 56, 615–649 (1987).PubMedCrossRefGoogle Scholar
  8. 8.
    Levitzki, A. Science 241, 800–806 (1988).PubMedCrossRefGoogle Scholar
  9. 9.
    Fleishman, L.F., Chahwala, S.B. & Cantley, L. Science 231, 407–410 (1986).CrossRefGoogle Scholar
  10. 10.
    Wakelam, M.J.O., Davies, S.A., Houslay, M.D., McKay. I ., Marshall, C.J. & Hall, A. Nature 323, 173–176 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    Bar-Sagi, D. & Feramisco, J.R. Science 233, 1061–1068 (1986).PubMedCrossRefGoogle Scholar
  12. 12.
    Hanley, M.R. & Jackson, T. Nature 328, 668–669.Google Scholar
  13. 13.
    Lacal, J.C., Moscat, J. & Aaronson, S.A. Nature 330, 269–272 (1987).PubMedCrossRefGoogle Scholar
  14. 14.
    Whyte, P., Buchkowich, K.J., Horowitz, J.M., Friend, S.H., Raybuck, M., Weinberg, R.A. & Harlow, E. Nature 334, 124–129 (1988).PubMedCrossRefGoogle Scholar
  15. 15.
    Courtneidge, S.A. & Smith, A.E. Nature 303, 435–439 (1983).PubMedCrossRefGoogle Scholar
  16. 16.
    Chiu, R., Boyle, W.J., Meek, J., Smeal, T., Hunter, T. & Karin, M. Cell 54, 541–552 (1988).PubMedCrossRefGoogle Scholar
  17. 17.
    Sassone-Corsi, P., Lamph, W.W., Kamps, M. & Verma, I .M. Cell 54, 553–560 (1988).PubMedCrossRefGoogle Scholar
  18. 18.
    Downward, J., de Gunzburg, J., Riehl, R. & Weinberg, R.A. Proc Natl,Acad.Sci. USA 85, 5774–5778 (1988).CrossRefGoogle Scholar
  19. 19.
    Roth, R.A. & Pierce, S.B. Biochemistry 26, 4179–4182 (1987).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Jean de Gunzburg
    • 1
  • Rebecca Riehl
    • 2
  • Robert A. Weinberg
    • 2
  1. 1.Faculté de Médecine LariboisièreUnité INSERM U-248ParisFrance
  2. 2.Whitehead Institute9 Cambridge CenterCambridgeUSA

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