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Cell Growth and Development

The Ras Mutant D119N Is Both Dominant Negative and Activated

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Pages 6297-6305 | Received 13 Oct 1998, Accepted 17 Jun 1999, Published online: 27 Mar 2023

REFERENCES

  • Akiyamo, Y., and J. 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.
  • Bauer, B., G. Mirey, I. R. Vetter, J. A. García-Ranea, A. Valencia, A. Wittinghofer, J. H. Camonis, and J. Cool 1999. Effector recognition by the small GTP-binding proteins Ras and Ral. J. Biol. Chem. 274:17763–17770.
  • Boguski, M. S., and J. McCormick 1993. Proteins regulating Ras and its relatives. Nature 366:643–654.
  • 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.
  • Bourne, H. R., D. A. Sanders, and J. McCormick 1990. The GTPase superfamily: a conserved switch for diverse cell functions. Nature 348:125–132.
  • Cai, H., J. Szeberényi, and J. Cooper 1990. Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells. Mol. Cell. Biol. 10:5314–5323.
  • Cool, R. H. Unpublished data.
  • Cowley, S., H. Paterson, P. Kemp, and 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.
  • DeFeo-Jones, D., K. Tatchell, L. C. Robinson, I. S. Sigal, W. C. Vass, D. R. Lowy, and J. Scolnick 1985. Mammalian and yeast ras gene products: biological function in their heterologous systems. Science 228:179–184.
  • De Rooij, J., F. J. T. Zwartkruis, M. H. G. Verheijen, R. H. Cool, S. M. B. Nijman, A. Wittinghofer, and J. Bos 1998. Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396:474–477.
  • Esser, D., B. Bauer, R. M. F. Wolthuis, A. Wittinghofer, R. H. Cool, and J. Bayer 1998. Structure determination of the Ras-binding domain of the Ral-specific exchange factor Rlf. Biochemistry 37:13453–13462.
  • Farnsworth, C. L., and J. Feig 1991. Dominant inhibitory mutations in the Mg2+-binding site of RasH prevent its activation by GTP. Mol. Cell. Biol. 11:4822–4829.
  • Feig, L. A., and J. Cooper 1988. Inhibition of NIH 3T3 cell proliferation by a mutant ras protein with preferential affinity for GDP. Mol. Cell. Biol. 8:3235–3243.
  • Feig, L. A., B.-T. Pan, T. M. Roberts, and J. Cooper 1986. Isolation of ras GTP-binding mutants using an in situ colony-binding assay. Proc. Natl. Acad. Sci. USA 83:4607–4611.
  • Goi, T., G. Rusanescu, T. Urano, and J. 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.
  • Han, M., and J. Sternberg 1991. Analysis of dominant-negative mutations of the Caenorhabditis elegans let-60 ras gene. Genes Dev. 5:2188–2198.
  • John, J., H. Rensland, I. Schlichting, I. Vetter, G. D. Borasio, R. S. Goody, and J. Wittinghofer 1993. Kinetic and structural analysis of the Mg2+-binding site of the guanine nucleotide-binding protein p21H-ras. J. Biol. Chem. 268:923–929.
  • Jones, S., R. J. Litt, C. J. Richardson, and J. Segev 1995. Requirement of nucleotide exchange factor for Ypt1 GTPase mediated protein transport. J. Cell Biol. 130:1051–1061.
  • Jung, V., W. Wei, R. Ballester, J. Camonis, S. Mi, L. Van Aelst, M. Wigler, and J. Broek 1994. Two types of RAS mutants that dominantly interfere with activators of RAS. Mol. Cell. Biol. 14:3707–3718.
  • Kataoka, T., S. Powers, S. Cameron, O. Fasano, M. Goldfarb, J. Broach, and J. Wigler 1985. Functional homology of mammalian and yeast RAS genes. Cell 40:19–26.
  • Khosravi-Far, R., M. A. White, J. K. Westwick, P. A. Solski, M. Chrzanowska-Wodnicka, L. Van Aelst, M. H. Wigler, and 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.
  • Kimura, K., S. Hattori, Y. Kabuyama, Y. Shizawa, J. Takayanagi, S. Nakamura, S. Toki, Y. Matsuda, K. Onodera, and J. Fukui 1994. Neurite outgrowth of PC12 cells is suppressed by wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase. J. Biol. Chem. 269:18961–18967.
  • Lenzen, C., R. H. Cool, and J. Wittinghofer 1995. Analysis of intrinsic and CDC25-stimulated guanine nucleotide exchange of p21ras-nucleotide complexes by fluorescence measurements. Methods Enzymol. 225:95–109.
  • Lenzen, C., R. H. Cool, H. Prinz, J. Kuhlmann, and J. Wittinghofer 1998. Kinetic analysis by fluorescence of the interaction between Ras and the catalytic domain of mouse guanine nucleotide exchange factor Cdc25Mm. Biochemistry 37:7420–7430.
  • Lenzen, C. U., and R. H. Cool. Unpublished data.
  • Leonardsen, L., J. E. DeClue, H. Lybaek, D. R. Lowy, and J. Willumsen 1996. Rasp21 sequences opposite the nucleotide binding pocket are required for GRF-mediated nucleotide release. Oncogene 13:2177–2187.
  • Miller, M., S. Prigent, E. Kupperman, L. Rioux, S.-H. Park, J. R. Feramisco, M. A. White, J. L. Rutkowski, and J. Meinkoth 1997. RalGDS functions in Ras- and cAMP-mediated growth stimulation. J. Biol. Chem. 272:5600–5605.
  • Mistou, M. Y., E. Jacquet, P. Poullet, H. Rensland, P. Gideon, I. Schlichting, A. Wittinghofer, and J. 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.
  • Munder, T., and J. Fürst 1992. The Saccharomyces cerevisiae CDC25 gene product binds specifically to catalytically inactive Ras proteins in vivo. Mol. Cell. Biol. 12:2091–2099.
  • Murai, H., M. Ikeda, S. Kishida, O. Ishida, M. Okazaki-Kishida, Y. Matsuura, and J. Kikuchi 1997. Characterization of Ral GDP dissociation stimulator-like (RGL) activities to regulate c-fos promoter and the GDP/GTP exchange of Ral. J. Biol. Chem. 272:10483–10490.
  • Okazaki, M., S. Kishida, T. Hinoi, T. Hasegawa, M. Tamada, T. Kataoka, and J. Kikuchi 1997. Synergistic activation of c-fos promoter activity by Raf and Ral GDP dissociation stimulator. Oncogene 14:515–521.
  • Powers, S., K. O’Neill, and J. 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.
  • Reinstein, J., I. Schlichting, M. Frech, R. S. Goody, and J. 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.
  • Ricketts, M. H., G. A. Durrheim, H. M. North, M. J. van der Merwe, and J. Levinson 1996. Positive and negative modulation of H-ras transforming potential by mutations of phenylalanine-28. Mol. Biol. Rep. 23:109–117.
  • Roche, S., J. Downward, P. Raynal, and J. 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.
  • 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.
  • Sambrook, J., E. F. Fritsch, T. Maniatis 1989. Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press, New York, N.Y.
  • Schlichting, I., S. C. Almo, G. Rapp, K. Wilson, K. Petratos, A. Lentfer, A. Wittinghofer, W. Kabsch, E. M. Pai, G. A. Petsko, and J. Goody 1990. Time-resolved X-ray crystallographic study of the conformational change in Ha-Ras p21 protein on GTP hydrolysis. Nature 345:309–315.
  • Schmidt, G. Unpublished results.
  • Schmidt, G., C. Lenzen, I. Simon, R. Deuter, R. H. Cool, R. S. Goody, and J. Wittinghofer 1996. Biochemical and biological consequences of changing the specificity of p21ras from guanosine to xanthosine nucleotides. Oncogene 12:87–96.
  • Schweighoffer, F., H. Cai, C. Chevallier-Multon, I. Fath, G. Cooper, and J. 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.
  • Shirouzu, M., H. Koide, J. Fujita-Yoshigaki, H. Oshio, Y. Toyama, K. Yamasaki, S. Fuhrman, E. Villafranca, Y. Kaziro, and J. Yokoyama 1994. Mutations that abolish the ability of Ha-Ras to associate with Raf-1. Oncogene 9:2153–2157.
  • Sigal, I. S., J. B. Gibbs, J. S. D’Alonzo, G. L. Temeles, B. S. Wolanski, S. H. Socher, and J. Scolnick 1986. Mutant ras-encoded proteins with altered nucleotide binding exert dominant biological effects. Proc. Natl. Acad. Sci. USA 83:952–956.
  • Stacey, D. W., L. A. Feig, and J. Gibbs 1991. Dominant inhibitory Ras mutants selectively inhibit the activity of either cellular or oncogenic Ras. Mol. Cell. Biol. 11:4053–4064.
  • Trahey, M., and J. McCormick 1987. A cytoplasmatic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants. Science 238:542–545.
  • Van den Berghe, N., R. H. Cool, G. Horn, and J. 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.
  • Van den Berghe, N., R. H. Cool, and J. Wittinghofer 1999. Discriminatory residues in Ras and Rap for guanine nucleotide exchange factor recognition. J. Biol. Chem. 271:11078–11085.
  • Vossler, M. R., H. Yao, R. D. York, M.-G. Pan, C. S. Rim, and J. Stork 1997. cAMP activates MAP kinase and Elk-1 through a B-Raf- and Rap1-dependent pathway. Cell 89:73–82.
  • Walker, F., A. Kato, L. J. Gonez, M. L. Hibbs, N. Pouliot, A. Levitzki, and J. 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.
  • Walter, M., S. G. Clark, and J. Levinson 1986. The oncogenic activation of human p21ras by a novel mechanism. Science 233:649–652.
  • White, M. A., C. Nicolette, A. Minden, A. Polverino, L. van Aelst, M. Karin, and J. Wigler 1995. Multiple Ras functions can contribute to mammalian cell transformation. Cell 80:533–541.
  • White, M. A., T. Vale, J. H. Camonis, E. Schaefer, and J. Wigler 1996. A role for the Ral guanine nucleotide dissociation stimulator in mediating Ras-induced transformation. J. Biol. Chem. 271:16439–16442.
  • Wolthuis, R. M. F., N. de Ruiter, R. H. Cool, and J. Bos 1997. Stimulation of gene induction and cell growth by the Ras effector Rlf. EMBO J. 16:6748–6761.
  • Yamasaki, K., M. Shirouza, Y. Muto, J. Fujita-Yoshigaki, H. Koide, Y. Ito, G. Kawai, S. Hattori, S. Yokoyama, S. Nishimura, and J. 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.
  • Yang, J.-J., J.-S. Kang, and J. Krauss 1998. Ras signals to the cell cycle machinery via multiple pathways to induce anchorage-independent growth. Mol. Cell. Biol. 18:2586–2595.
  • York, R. D., H. Yao, T. Dillon, C. L. Ellig, S. P. Ecker, E. W. McCleskey, and J. Stork 1998. Rap1 mediates sustained MAP kinase activation induced by nerve growth factor. Nature 392:622–626.
  • Zhong, J.-M., M.-C. Chen-Hwang, and J. Hwang 1995. Switching nucleotide specificity of Ha-ras p21 by a single amino acid substitution at aspartate 119. J. Biol. Chem 270:10002–10007.
  • Ziman, M., J. M. O’Brien, L. A. Quellette, W. R. Church, and J. 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.

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