The Ras mutant D119N is both dominant negative and activated

Molecular and Cellular Biology

Volumn 19, Issue 9, 1999, Pages 6297-6305

  Cool, Robbert H ^a,b   Schmidt, Gudula ^a,c   Lenzen, Christian U ^a   Prinz, Heino ^a   Vogt, Dorothee ^a   Wittinghofer, Alfred ^a  

^a MAX PLANCK INSTITUTE OF MOLECULAR PHYSIOLOGY   (Germany)

^b UNIVERSITY OF GRONINGEN   (Netherlands)

^c UNIVERSITY OF FREIBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE TRIPHOSPHATE; MUTANT PROTEIN; NUCLEOTIDE; RAS PROTEIN;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; CELL STRAIN 3T3; CONTROLLED STUDY; DNA SYNTHESIS; MOUSE; MUTATION; NERVE FIBER GROWTH; NONHUMAN; PHEOCHROMOCYTOMA CELL; PRIORITY JOURNAL; RAT;

EID: 0032795870     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.19.9.6297     Document Type: Article

References (58)

1. Akiyamo, Y., and K. Ito. 1990. SecY protein, a membrane-embedded secretion factor of E. coli, is cleaved by the OmpT protease in vitro. Biochem. Biophys. Res. Commun. 167:711-715.
2. Bauer, B., G. Mirey, I. R Vetter, J. A. García-Ranea, A. Valencia, A. Wittinghofer, J. H. Camonis, and R. H. Cool. 1999. Effector recognition by the small GTP-binding proteins Ras and Ral. J. Biol. Chem. 274:17763-17770.
3. Boguski, M. S., and F. McCormick. 1993. Proteins regulating Ras and its relatives. Nature 366:643-654.
4. Boriack-Sjodin, P. A., S. M. Margarit, D. Bar-Sagi, and J. Kuriyan. 1998. The structural basis of the activation of Ras by Sos. Nature 394:337-343.
5. Bourne, H. R., D. A. Sanders, and F. McCormick. 1990. The GTPase superfamily: a conserved switch for diverse cell functions. Nature 348:125-132.
6. Cai, H., J. Szeberényi, and G. M. Cooper. 1990. Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells. Mol. Cell. Biol. 10:5314-5323.
7. 6a. Cool, R. H. Unpublished data.
8. Cowley, S., H. Paterson, P. Kemp, and C. J. Marshall. 1994. Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell 77:841-852.
9. DeFeo-Jones, D., K. Tatchell, L. C. Robinson, I. S. Sigal, W. C. Vass, D. R. Lowy, and E. M. Scolnick. 1985. Mammalian and yeast ras gene products: biological function in their heterologous systems. Science 228:179-184.
10. De Rooij, J., F. J. T. Zwartkruis, M. H. G. Verheijen, R. H. Cool, S. M. B. Nijmaa, A. Wittinghofer, and J. L. Bos. 1998. Epac is a Rap1 guanine- nucleotide-exchange factor directly activated by cyclic AMP. Nature 396: 474-477.
11. Esser, D., B. Bauer, R. M. F. Wolthuis, A. Wittinghofer, R. H. Cool, and P. Bayer. 1998. Structure determination of the Ras-binding domain of the Ral-specific exchange factor Rlf. Biochemistry 37:13453-13462.
12. H prevent its activation by GTP. Mol. Cell. Biol. 11:4822-4829.
13. Feig, L. A., and G. M. Cooper. 1988. Inhibition of NIH 3T3 cell proliferation by a mutant ras protein with preferential affinity for GDP. Mol. Cell. Biol. 8:3235-3243.
14. Feig, L. A., B.-T. Pan, T. M. Roberts, and G. M. Cooper. 1986. Isolation of ras GTP-binding mutants using an in situ colony-binding assay. Proc. Natl. Acad. Sci. USA 83:4607-4611.
15. Goi, T., G. Rusanescu, T. Urano, and L. A. Feig. 1999. Ral-specific guanine nucleotide exchange factor activity opposes other Ras effectors in PC12 cells by inhibiting neurite outgrowth. Mol. Cell. Biol. 19:1731-1741.
16. Han, M., and P. W. Sternberg. 1991. Analysis of dominant-negative mutations of the Caenorhabditis elegans let-60 ras gene. Genes Dev. 5:2188-2198.
17. H-ras. J. Biol. Chem. 268:923-929.
18. Jones, S., R. J. Litt, C. J. Richardson, and N. Segev. 1995. Requirement of nucleotide exchange factor for Ypt1 GTPase mediated protein transport. J. Cell Biol. 130:1051-1061.
19. Jung, V., W. Wei, R. Ballester, J. Camonis, S. Mi, L. Van Aelst, M. Wigler, and D. Broek. 1994. Two types of RAS mutants that dominantly interfere with activators of RAS. Mol. Cell. Biol. 14:3707-3718.
20. Kataoka, T., S. Powers, S. Cameron, O. Fasano, M. Goldfarb, J. Broach, and M. Wigler. 1985. Functional homology of mammalian and yeast RAS genes. Cell 40:19-26.
21. Khosravi-Far, R., M. A. White, J. K. Westwick, P. A. Solski, M. Chrzanowska-Wodnicka, L. Van Aelst, M. H. Wigler, and C. J. Der. 1996. Oncogenic Ras activation of Raf/mitogen-activated protein kinase-independent pathways is sufficient to cause tumorigenic transformation. Mol. Cell. Biol. 16:3923-3933.
22. Kimura, K., S. Hattori, Y. Kabuyama, Y. Shizawa, J. Takayanagi, S. Nakamura, S. Toki, Y. Matsuda, K. Onodera, and Y. Fukui. 1994. Neurite outgrowth of PC12 cells is suppressed by wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase. J. Biol. Chem. 269:18961-18967.
23. Lenzen, C., R. H. Cool, and A. Wittinghofer. 1995. Analysis of intrinsic and CDC25-stimulated guanine nucleotide exchange of p21ras-nucleotide complexes by fluorescence measurements. Methods Enzymol. 225:95-109.
24. Mm. Biochemistry 37:7420-7430.
25. Lenzen, C. U., and R. H. Cool. Unpublished data.
26. Leonardsen, L., J. E. DeClue, H. Lybaek, D. R. Lowy, and B. M. Willumsen. 1996. Rasp21 sequences opposite the nucleotide binding pocket are required for GRF-mediated nucleotide release. Oncogene 13:2177-2187.
27. Miller, M., S. Prigent, E. Kupperman, L. Rioux, S.-H. Park, J. R. Feramisco, M. A. White, J. L. Rutkowski, and J. L. Meinkoth. 1997. RalGDS functions in Ras- and cAMP-mediated growth stimulation. J. Biol. Chem. 272:5600-5605.
28. Mistou, M. Y., E. Jacquet, P. Poullet, H. Rensland, P. Gideon, I. Schlichting, A. Wittinghofer, and A. Parmeggiani. 1992. Mutations of Ha-ras p21 that define important regions for the molecular mechanism of the SDC25 C-domain, a guanine nucleotide dissociation stimulator. EMBO J. 11:2391-2397.
29. Munder, T., and P. Fürst 1992. The Saccharomyces cerevisiae CDC25 gene product binds specifically to catalytically inactive Ras proteins in vivo. Mol. Cell. Biol. 12:2091-2099.
30. Mural, H., M. Ikeda, S. Kishida, O. Ishida, M. Okazaki-Kishida, Y. Matsuura, and A. Kikuchi. 1997. Characterization of Ral GDP dissociation stimulator-like (RGL) activities to regulate c-fos promoter and the GDP/ GTP exchange of RaI. J. Biol. Chem. 272:10483-10490.
31. Okazaki, M., S. Kishida, T. Hinoi, T. Hasegawa, M. Tamada, T. Kataoka, and A. Kikuchi. 1997. Synergistic activation of c-fos promoter activity by Raf and Ral GDP dissociation stimulator. Oncogene 14:515-521.
32. Powers, S., K. O'Neill, and M. Wigler. 1989. Dominant yeast and mammalian RAS mutants that interfere with the CDC25-dependent activation of wild-type RAS in Saccharomyces cerevisiae. Mol. Cell. Biol. 9:390-395.
33. Reinstein, J., I. Schlichting, M. Frech, R. S. Goody, and A. Wittinghofer. 1991. p21 with a phenylalanine 28→leucine mutation reacts normally with the GTPase activating protein GAP but nevertheless has transforming properties. J. Biol. Chem. 266:17700-17706.
34. Ricketts, M. H., G. A. Durrheim, H. M. North, M. J. van der Merwe, and A. D. Levinson. 1996. Positive and negative modulation of H-ras transforming potential by mutations of phenylalanine-28. Mol. Biol. Rep. 23:199-117.
35. Roche, S., J. Downward, P. Raynal, and S. A. Courtneidge. 1998. A function for phosphatidylinositol 3-kinase β (p85α-p110β) in fibroblasts during mitogenesis: requirement for insulin- and lysophosphatidic acid-mediated signal transduction. Mol. Cell. Biol. 18:7119-7129.
36. Rodriguez-Viciana, P., P. H. Warne, A. Khwaja, B. M. Marte, D. Pappin, P. Das, M. D. Waterfield, A. Ridley, and J. Downward. 1997. Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras. Cell 89:457-467.
37. Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press, New York, N.Y.
38. Schlichting, I., S. C. Almo, G. Rapp, K. Wilson, K. Petratos, A. Lentfer, A. Wittinghofer, W. Kabsch, E. M. Pai, G. A. Petsko, and R. S. Goody. 1990. Time-resolved X-ray crystallographic study of the conformational change in Ha-Ras p21 protein on GTP hydrolysis. Nature 345:309-315.
39. Schmidt, G. Unpublished results.
40. Schmidt, G., C. Lenzen, I. Simon, R. Deuter, R. H. Cool, R. S. Goody, and A. Wittinghofer. 1996. Biochemical and biological consequences of changing the specificity of p21ras from guanosine to xanthosine nucleotides. Oncogene 12:87-96.
41. Schweighoffer, F., H. Cai, C. Chevallier-Multon, I. Fath, G. Cooper, and B. Tocque. 1993. The Saccharomyces cerevisiae SDC25 C-domain gene product overcomes the dominant inhibitory activity of Ha-Ras Asn-17. Mol. Cell. Biol. 13:39-43.
42. Shirouzu, M., H. Koide, J. Fujita-Yoshigaki, H. Oshio, Y. Toyama, K. Yamasaki, S. Fuhrman, E. Villafranca, Y. Kaziro, and S. Yokoyama. 1994. Mutations that abolish the ability of Ha-Ras to associate with Raf-1. Oncogene 9:2153-2157.
43. Sigal, I. S., J. B. Gibbs, J. S. D'Alonzo, G. L. Temeles, B. S. Wolanski, S. H. Socher, and E. M. Scolnick. 1986. Mutant ras-encoded proteins with altered nucleotide binding exert dominant biological effects. Proc. Natl. Acad. Sci. USA 83:952-956.
44. Stacey, D. W., L. A. Feig, and J. B. Gibbs. 1991. Dominant inhibitory Ras mutants selectively inhibit the activity of either cellular or oncogenic Ras. Mol. Cell. Biol. 11:4053-4064.
45. Trahey, M., and F. McCormick. 1987. A cytoplasmatic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants. Science 238:542-545.
46. Van den Berghe, N., R. H. Cool, G. Horn, and A. Wittinghofer. 1997. Biochemical characterization of C3G: an exchange factor that discriminates between Rap1 and Rap2 and is not inhibited by Rap1A(S17N). Oncogene 15:845-850.
47. Van den Berghe, N., R. H. Cool, and A. Wittinghofer. 1999. Discriminatory residues in Ras and Rap for guanine nucleotide exchange factor recognition. J. Biol. Chem. 271:11078-11085.
48. Vossler, M. R., H. Yao, R. D. York, M.-G. Pan, C. S. Rim, and P. J. S. Stork. 1997. cAMP activates MAP kinase and Elk-1 through a B-Raf- and Rap1-dependent pathway. Cell 89:73-82.
49. Walker, F., A. Kato, L. J. Gonez, M. L. Hibbs, N. Pouliot, A. Levitzki, and A. W. Burgess. 1998. Activation of the Ras/mitogen-activated protein kinase pathway by kinase-defective epidermal growth factor receptors results in cell survival but not proliferation. Mol. Cell. Biol. 18:7192-7204.
50. ras by a novel mechanism. Science 233:649-652.
51. White, M. A., C. Nicolette, A. Minden, A. Polverino, L. van Aelst, M. Karin, and M. H. Wigler. 1995. Multiple Ras functions can contribute to mammalian cell transformation. Cell 80:533-541.
52. White, M. A., T. Vale, J. H. Camonis, E. Schaefer, and M. H. Wigler. 1996. A role for the RaI guanine nucleotide dissociation stimulator in mediating Ras-induced transformation. J. Biol. Chem. 271:16439-16442.
53. Wolthuis, R. M. F., N. de Ruiter, R. H. Cool, and J. L. Bos. 1997. Stimulation of gene induction and cell growth by the Ras effector Rlf. EMBO J. 16:6748-6761.
54. Yamasaki, K., M. Shirouza, Y. Muto, J. Fujita-Yoshigaki, H. Koide, Y. Ito, G. Kawai, S. Hattori, S. Yokoyama, S. Nishimura, and T. Miyazawa. 1994. Site-directed mutagenesis, fluorescence, and two-dimensional NMR studies on microenvironments of effector region aromatic residues of human c-Ha-Ras protein. Biochemistry 33:65-73.
55. Yang, J.-J., J.-S. Kang, and R. S. Krauss. 1998. Ras signals to the cell cycle machinery via multiple pathways to induce anchorage-independent growth. Mol. Cell. Biol. 18:2586-2595.
56. York, R. D., H. Yao, T. Dillon, C. L. Ellig, S. P. Ecker, E. W. McCleskey, and P. J. S. Stork. 1998. Rap1 mediates sustained MAP kinase activation induced by nerve growth factor. Nature 392:622-626.
57. Zhong, J.-M., M.-C. Chen-Hwang, and Y.-W. Hwang. 1995. Switching nucleotide specificity of Ha-ras p21 by a single amino acid substitution at aspartate 119. J. Biol. Chem 270:10002-10007.
58. Ziman, M., J. M. O'Brien, L. A. Quellette, W. R. Church, and D. I. Johnson. 1991. Mutational analysis of CDC42Sc, a Saccharomyces cerevisiae gene that encodes a putative GTP-binding protein involved in the control of cell polarity. Mol. Cell. Biol. 11:3537-3544.