Abstract
Ras and Rap1 GTPases require Gly12, the effector domain (residues 32 to 40) and Ala 59 for activation by GAP1 and GAP3, respectively. The replacement of Gly12 by Val or Ala59 by Thr potentiates the Ras oncogenicity and Rap anti-oncogenicity. However, the mutations in the effector domain, in particular the replacement of Thr35 by Ala, abolishes both Ras oncogenicity and Rap anti-oncogenicity, indicating that the effector domains are involved in the interactions of these signal transducers with their targets as well as the GAPs. Here, we demonstrate that replacement of Tyr64 of the HaRas protein or Phe64 of Rap1A protein by Glu reduces their intrinsic GTPase activities and abolishes their stimulation by GAP1 or GAP3, respectively. Further mutational analysis has revealed that only the Tyr to Phe or Leu (Ras) and Phe to Tyr (Rap1A) substitutions at position 64 still allow these GTPases to be activated by GAPs.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Barbacid, M. (1987) Ann. Rev. Blochem. 56, 779–827.
Pizon, V., Chardin, P., Lerosey, I., Olofsson, B. and Tavitian, A. (1988) Oncogene 3, 201–204.
Kitayama, H., Sugimoto, Y., Matsuzaki, T., Ikawa, Y. and Noda, M. (1989) Cell 56, 77–84.
Pizon, V., Lerosey, I., Chardin, P. and Tavitian, A. (1988) Nucleic Acids Res. 16, 7719.
Ohmstede, C.A., Farrell, F.X., Reep, B.R., Clemetson, K.J. and Lapetina, E.G. (1990). Proc. Natl. Acad. Sci. USA 87, 6527–6531.
Kitayama, H., Matsuzaki, T., Ikawa, Y. and Noda, M. (1990) Proc. Natl. Acad. Sci. USA 87, 4284–4288.
Trahey, M. and McCormick, F. (1987) Science 238, 542–545.
Kikuchi, A., Sasaki, T., Araki, S., Hata, Y. and Takai, Y. (1989) J. Biol. Chem. 264, 9133–9136.
Adari, H., Lowy, D.R., Willumsen, B.M., Der, C.J., and McCormick, F. (1988) Science 240, 518–521.
Cales, C., Hancock, J.F., Marshall, C.J. and Hall, A. (1988) Nature 332, 548–551.
Quilliam, L.A., Der, C.J., Clark, R., O’Rourke, E.G., Zhang, K., McCormick, F. and Bokoch, G.M. (1990) Mol. Cell. Biol. 10, 2901–2908.
Maruta, H., Holden, J., Sizeland, A. and D’Abaco, G. (1991) J. Biol. Chem. in press.
Sigal, I.S., Gibbs, J.A., D’Alonzo, J.S., and Scolnick, E.M. (1986). Proc. Natl. Acad. Sci. USA 83, 4725–4729.
Willumsen, B.M., Papageorge, A.G., Kung, H.F., Bekesi, E., Robins, T., Johnsen, M., Vass, W.C. and Lowy, D.R. (1986). Mol. Cell Biol. 6, 2646–2654.
Gibbs, J.B., Schaber, M.D., Schofield, T.L., Scolnick, E.M. and Sigal, I.S. (1989) Proc. Natl. Acad. Sci. USA 86, 6630–6634.
Fasano, O., Aldrich, F., Tamanoi, E., Taparowsky, M., Furth, M. and Wigier, M. (1984) Proc. Natl. Acad. Sci. USA 81, 4008–4012.
Baldwin, G.S., Stanley, I.J. and Nice, E.C. (1983) FEBS Letter 153, 257–261.
Srivastava, S.K., Donato, D.A. and Lacal, J.C. (1990) Mol. Cell. Biol. 9, 1779–1783.
Lowe, D.G., Capon, D.J., Delwart, E., Sakaguchi, A. Y., Naylor, S.L. and Goeddel, D.V. (1987) Cell 48, 137–165.
Lowe, D.G., Ricketts, M., Levinson, A.D. and Goeddel, D.V. (1988) Proc. Natl. Acad. Sci. USA Proc. Natl. Acad. Sci. USA 85, 1015–1019.
Garret, M.D., Self, A.J., Van Oers, C. and Hall, A. (1989) J. Biol. Chem. 264, 10–13.
Smith, D.B. and Johnson, K.S. (1988) Gene 67, 31–40.
Maruta, H. (1989) In ras Oncogenes (Spandidos, D.A. ed.), Plenum Publishing Co., New York, pp255–260.
Brandt, D.R., Asano, T., Pedersen, S.T. and Ross, E.M. (1983) Biochemistry 22, 4357–4362.
Bradford, M.M. (1976) Anal. Biochem. 72, 248–254.
Beitel, G.J., Clark, S.G. and Horvitz, H.R. (1990) Nature 348, 503–509.
Holden, J., Nur-E-Kamal, M.S.A., Fabri, L., Nice, E., Hammacher, A. and Maruta, H. (1991) J. Biol. Chem. 266, In Press.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Plenum Press, New York
About this chapter
Cite this chapter
Nur-E-Kamal, M.S.A., Maruta, H. (1991). ras and rap1 GTPases Mutated at Position 64. In: Spandidos, D.A. (eds) The Superfamily of ras-Related Genes. NATO ASI Series, vol 220. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-6018-6_12
Download citation
DOI: https://doi.org/10.1007/978-1-4684-6018-6_12
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-6020-9
Online ISBN: 978-1-4684-6018-6
eBook Packages: Springer Book Archive