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Cell Growth and Development

A Ral Guanine Exchange Factor-Ral Pathway Is Conserved in Drosophila melanogaster and Sheds New Light on the Connectivity of the Ral, Ras, and Rap Pathways

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Pages 1112-1124 | Received 29 Apr 2002, Accepted 21 Oct 2002, Published online: 27 Mar 2023

REFERENCES

  • Adams, M. D., S. E. Celniker, R. A. Holt, C. A. Evans, J. D. Gocayne, P. G. Amanatides, S. E. Scherer, P. W. Li, R. A. Hoskins, R. F. Galle, R. A. George, S. E. Lewis, S. Richards, M. Ashburner, S. N. Henderson, G. G. Sutton, J. R. Wortman, M. D. Yandell, Q. Zhang, L. X. Chen, R. C. Brandon, Y. H. Rogers, R. G. Blazej, M. Champe, B. D. Pfeiffer, K. H. Wan, C. Doyle, E. G. Baxter, G. Helt, C. R. Nelson, G. L. Gabor Miklos, J. F. Abril, A. Agbayani, H. J. An, C. Andrews-Pfannkoch, D. Baldwin, R. M. Ballew, A. Basu, J. Baxendale, L. Bayraktaroglu, E. M. Beasley, K. Y. Beeson, P. V. Benos, B. P. Berman, D. Bhandari, S. Bolshakov, D. Borkova, M. R. Botchan, J. Bouck, P. Brokstein, P. Brottier, K. C. Burtis, D. A. Busam, H. Butler, E. Cadieu, A. Center, I. Chandra, J. M. Cherry, S. Cawley, C. Dahlke, L. B. Davenport, P. Davies, B. de Pablos, A. Delcher, Z. Deng, A. D. Mays, I. Dew, S. M. Dietz, K. Dodson, L. E. Doup, M. Downes, S. Dugan-Rocha, B. C. Dunkov, P. Dunn, K. J. Durbin, C. C. Evangelista, C. Ferraz, S. Ferriera, W. Fleischmann, C. Fosler, A. E. Gabrielian, N. S. Garg, W. M. Gelbart, K. Glasser, A. Glodek, F. Gong, J. H. Gorrell, Z. Gu, P. Guan, M. Harris, N. L. Harris, D. Harvey, T. J. Heiman, J. R. Hernandez, J. Houck, D. Hostin, K. A. Houston, T. J. Howland, M. H. Wei, C. Ibegwam, et al. 2000. The genome sequence of Drosophila melanogaster. Science 287: 2185–2195.
  • Asha, H., N. D. de Ruiter, M. G. Wang, and I. K. Hariharan. 1999. The Rap1 GTPase functions as a regulator of morphogenesis in vivo. EMBO J. 18: 605–615.
  • Barbacid, M. 1987. ras genes. Annu. Rev. Biochem. 56: 779–827.
  • Bergmann, A., J. Agapite, K. McCall, and H. Steller. 1998. The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling. Cell 95: 331–341.
  • Bhattacharya, M., P. H. Anborgh, A. V. Babwah, L. B. Dale, T. Dobransky, J. L. Benovic, R. D. Feldman, J. M. Verdi, R. J. Rylett, and S. S. G. Ferguson. 2002. β-Arrestins regulate a Ral-GDS-Ral effector pathway that mediates cytoskeletal reorganization. Nat. Cell Biol. 4: 547–555.
  • Bohni, R., J. Riesgo-Escovar, S. Oldham, W. Brogiolo, H. Stocker, B. F. Andruss, K. Beckingham, and E. Hafen. 1999. Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell 97: 865–875.
  • Bourne, H. R., D. A. Sanders, and F. McCormick. 1990. The GTPase superfamily: a conserved switch for diverse cell functions. Nature 348: 125–132.
  • Brand, A. H., and N. Perrimon. 1993. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118: 401–415.
  • Brown, N. H., and F. C. Kafatos. 1988. Functional cDNA libraries from Drosophila embryos. J. Mol. Biol 203: 425–437.
  • Brymora, A., V. A. Valova, M. R. Larsen, B. D. Roufogalis, and P. J. Robinson. 2001. The brain exocyst complex interacts with RalA in a GTP-dependent manner: identification of a novel mammalian Sec3 gene and a second Sec15 gene. J. Biol. Chem. 276: 29792–29797.
  • Cantor, S. B., T. Urano, and L. A. Feig. 1995. Identification and characterization of Ral-binding protein 1, a potential downstream target of Ral GTPases. Mol. Cell. Biol. 15: 4578–4584.
  • Capdevila, J. A., and I. Guerrero. 1994. Targeted expression of the signaling molecule Decapentaplegic induces pattern duplications and growth alterations in Drosophila wings. EMBO J. 13: 4459–4468.
  • Caron, E., A. J. Self, and A. Hall. 2000. The GTPase Rap1 controls functional activation of macrophage integrin alphaMbeta2 by LPS and other inflammatory mediators. Curr. Biol. 10: 974–978.
  • Chardin, P., and A. Tavitian. 1986. The ral gene: a new related gene isolated by the use of a synthetic probe. EMBO J. 5: 2203–2208.
  • Culi, J., E. Martin-Blanco, and J. Modolell. 2001. The EGF receptor and N signalling pathways act antagonistically in Drosophila mesothorax bristle patterning. Development 128: 299–308.
  • Deak, P., M. M. Omar, R. D. Saunders, M. Pal, O. Komonyi, J. Szidonya, P. Maroy, Y. Zhang, M. Ashburner, P. Benos, C. Savakis, I. Siden-Kiamos, C. Louis, V. N. Bolshakov, F. C. Kafatos, E. Madueno, J. Modolell, and D. M. Glover. 1997. P-element insertion alleles of essential genes on the third chromosome of Drosophila melanogaster: correlation of physical and cytogenetic maps in chromosomal region 86E-87F. Genetics 147: 1697–1722.
  • de Bruyn, K. M. T., J. de Rooij, R. M. F. Wolthuis, H. Rehmann, J. Wesenbeek, R. H. Cool, A. H. Wittinghofer, and J. L. Bos. 2000. RalGEF2, a pleckstrin homology domain containing guanine nucleotide exchange factor for Ral. J. Biol. Chem. 275: 29761–29766.
  • Falquet, L., M. Pagni, P. Bucher, N. Hulo, C. J. Sigrist, K. Hofmann, and A. Bairoch. 2002. The PROSITE database, its status in 2002. Nucleic Acids Res. 30: 235–238.
  • Frankel, P., M. Ramos, J. Flom, S. Bychenok, T. Joseph, E. Kerkhoff, U. R. Rapp, L. A. Feig, and D. A. Foster. 1999. Ral and Rho-dependent activation of phospholipase D in v-Raf-transformed cells. Biochem. Biophys. Res. Commun. 255: 502–507.
  • Gildea, J. J., M. A. Harding, M. J. Seraj, K. M. Gulding, and D. Theodorescu. 2002. The role of Ral A in epidermal growth factor receptor-regulated cell motility. Cancer Res. 62: 982–985.
  • 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.
  • Halfar, K., C. Rommel, H. Stocker, and E. Hafen. 2001. Ras controls growth, survival and differentiation in the Drosophila eye by different thresholds of MAP kinase activity. Development 128: 1687–1696.
  • Hamad, N. M., J. H. Elconin, A. E. Karnoub, W. Bai, J. N. Rich, R. T. Abraham, C. J. Der, and C. M. Counter. 2002. Distinct requirements for Ras oncogenesis in human versus mouse cells. Genes Dev. 16: 2045–2047.
  • Hay, B. A., R. Maile, and G. M. Rubin. 1997. P element insertion-dependent gene activation in the Drosophila eye. Proc. Natl. Acad. Sci. USA 94: 5195–5200.
  • Henry, D. O., S. A. Moskalenko, K. J. Kaur, M. Fu, R. G. Pestell, J. H. Camonis, and M. A. White. 2000. Ral GTPases contribute to regulation of cyclin D1 through activation of NF-kappaB. Mol. Cell. Biol. 20: 8084–8092.
  • Ikeda, M., O. Ishida, T. Hinoi, S. Kishida, and A. Kikuchi. 1998. Identification and characterization of a novel protein interacting with Ral-binding protein 1, a putative effector protein of Ral. J. Biol. Chem. 273: 814–821.
  • Jullien-Flores, V., O. Dorseuil, F. Romero, F. Letourneur, S. Saragosti, R. Berger, A. Tavitian, G. Gacon, and J. Camonis. 1995. Bridging the Ral GTPase to Rho pathways: RLIP76, a Ral effector with CDC42/Rac GTPase activating protein (GAP) activity. J. Biol. Chem. 270: 22473–22477.
  • Jullien-Flores, V., Y. Mahe, G. Mirey, C. Leprince, B. Meunier-Bisceuil, A. Sorkin, and J. H. Camonis. 2000. RLIP76, an effector of the GTPase Ral, interacts with the AP2 complex: involvement of the Ral pathway in receptor endocytosis. J. Cell Sci. 113: 2837–2844.
  • Karim, F. D., and G. M. Rubin. 1998. Ectopic expression of activated Ras1 induces hyperplastic growth and increased cell death in Drosophila imaginal tissues. Development 125: 1–9.
  • Kimmel, B. E., U. Heberlein, and G. M. Rubin. 1990. The homeo domain protein rough is expressed in a subset of cells in the developing Drosophila eye where it can specify photoreceptor cell subtype. Genes Dev. 4: 712–727.
  • Kishida, S., S. Koyama, K. Matsubara, M. Kishida, Y. Matsuura, and A. Kikuchi. 1997. Colocalization of Ras and Ral on the membrane is required for Ras-dependent Ral activation through Ral GDP dissociation stimulator. Oncogene 15: 2899–2907.
  • Kitayama, H., Y. Sugimoto, Y. Matsuzaki, Y. Ikawa, and M. Noda. 1989. A ras-related gene with transformation suppressor activity. Cell 56: 77–84.
  • Kurada, P., and K. White. 1998. Ras promotes cell survival in Drosophila by downregulating hid expression. Cell 95: 319–329.
  • Lee, T., L. Feig, and D. J. Montell. 1996. Two distinct roles for Ras in a developmentally regulated cell migration. Development 122: 409–418.
  • Leevers, S. J., D. Weinkove, L. K. MacDougall, E. Hafen, and M. D. Waterfield. 1996. The Drosophila phosphoinositide 3-kinase Dp110 promotes cell growth. EMBO J. 15: 6584–6594.
  • Letunic, I., L. Goodstadt, N. J. Dickens, T. Doerks, J. Schultz, R. Mott, F. Ciccarelli, R. R. Copley, C. P. Ponting, and P. Bork. 2002. Recent improvements to the SMART domain-based sequence annotation resource. Nucleic Acids Res. 30: 242–244.
  • Lu, X., T. B. Chou, N. G. Williams, T. Roberts, and N. Perrimon. 1993. Control of cell fate determination by p21ras/Ras1, an essential component of torso signaling in Drosophila. Genes Dev. 7: 621–632.
  • Matsubara, K., S. Kishida, Y. Matsuura, H. Kitayama, M. Noda, and A. Kikuchi. 1999. Plasma membrane recruitment of RalGDS is critical for Ras-dependent Ral activation. Oncogene 18: 1303–1312.
  • Moskalenko, S., D. O. Henry, C. Rosse, G. Mirey, J. H. Camonis, and M. A. White. 2002. The exocyst is a Ral effector complex. Nat. Cell Biol. 4: 66–72.
  • Nakao, K., and J. A. Campos-Ortega. 1996. Persistent expression of genes of the Enhancer of Split complex suppresses neural development in Drosophila. Neuron 16: 275–286.
  • Nakashima, S., K. Morinaka, S. Koyama, M. Ikeda, M. Kishida, K. Okawa, A. Iwamatsu, S. Kishida, and A. Kikuchi. 1999. Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors. EMBO J. 18: 3629–3642.
  • Osada, M., T. Tolkacheva, W. Li, T. O. Chan, P. N. Tsichlis, R. Saez, A. C. Kimmelman, and A. M. Chan. 1999. Differential roles of Akt, Rac, and Ral in R-Ras-mediated cellular transformation, adhesion, and survival. Mol. Cell. Biol. 19: 6333–6344.
  • Park, J. B. 2001. Regulation of GTP-binding state in RalA through Ca2+ and calmodulin. Exp. Mol. Med. 33: 54–58.
  • Park, S.-H., and R. A. Weinberg. 1996. A putative effector of Ral has homology to Rho/Rac GTPase activating proteins. Oncogene 11: 2349–2355.
  • Powers, S. K., 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.
  • Prober, D. A., and B. A. Edgar. 2000. Ras1 promotes cellular growth in the Drosophila wing. Cell 100: 435–446.
  • Rebhun, J. F., H. Chen, and L. A. Quilliam. 2000. Identification and characterization of a new family of guanine nucleotide exchange factors for the Ras-related GTPase Ral. J. Biol. Chem. 275: 13406–13410.
  • Rorth, P., K. Szabo, A. Bailey, T. Laverty, J. Rehm, G. M. Rubin, K. Weigmann, M. Milan, V. Benes, W. Ansorge, and S. M. Cohen. 1998. Systematic gain-of-function genetics in Drosophila. Development 125: 1049–1057.
  • Rosario, M., H. F. Paterson, and C. J. Marshall. 2001. Activation of the Ral and phosphatidylinositol 3′ kinase signaling pathways by the Ras-related protein TC21. Mol. Cell. Biol. 21: 3750–3762.
  • Rubin, G. M., L. Hong, P. Brokstein, M. Evans-Holm, E. Frise, M. Stapleton, and D. A. Harvey. 2000. A Drosophila complementary DNA resource. Science 287: 2222–2224.
  • Sambrook, J., and D. W. Russell. 2001. Molecular cloning: a laboratory manual, 3rd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
  • Sauer, F., D. A. Wassarman, G. M. Rubin, and R. Tjian. 1996. TAF(II)s mediate activation of transcription in the Drosophila embryo. Cell 87: 1271–1284.
  • Sawado, T., F. Hirose, Y. Takahashi, T. Sasaki, T. Shinomiya, K. Sakagushi, A. Matsukage, and M. Yamaguchi. 1998. The DNA replication-related element (DRE):DRE-binding factor system is a transcriptional regulator of the Drosophila E2F gene. J. Biol. Chem. 273: 26042–26051.
  • Sawamoto, K., P. Winge, S. Koyama, Y. Hirota, C. Yamada, S. Miyao, S. Yoshikawa, M. H. Jin, A. Kikuchi, and H. Okano. 1999. The Drosophila Ral GTPase regulates developmental cell shape changes through the Jun NH(2)-terminal kinase pathway. J. Cell. Biol. 146: 361–372.
  • Sawamoto, K., C. Yamada, S. Kishida, Y. Hirota, A. Tagushi, A. Kikuchi, and H. Okano. 1999. Ectopic expression of constitutively activated Ral GTPase inhibits cell shape changes during Drosophila eye development. Oncogene 18: 1967–1974.
  • Schmitt, J. M., and P. J. Stork. 2000. Beta 2-adrenergic receptor activates extracellular signal-regulated kinases (ERKs) via the small G protein rap1 and the serine/threonine kinase B-Raf. J. Biol. Chem. 275: 25342–25350.
  • Sebzda, E., M. Bracke, T. Tugal, N. Hogg, and D. A. Cantrell. 2002. Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling. Nat. Immunol. 3: 251–258.
  • Sugihara, K., S. Asano, K. Tanaka, A. Iwamatsu, K. Okawa, and Y. Ohta. 2001. The exocyst complex binds the small GTPase RalA to mediate filopodia formation. Nat. Cell Biol. 17: 17.
  • Suzuki, J., Y. Yamazaki, G. Li, Y. Kaziro, and H. Koide. 2000. Involvement of Ras and Ral in chemotactic migration of skeletal myoblasts. Mol. Cell. Biol. 20: 4658–4665.
  • Tatusova, T. A., and T. L. Madden. 1999. BLAST 2 sequences, a new tool for comparing protein and nucleotide sequences. FEMS Microbiol. Lett. 174: 247–250.
  • Tian, X., G. Rusanescu, W. Hou, B. Schaffhausen, and L. A. Feig. 2002. PDK1 mediates growth factor-induced Ral-GEF activation by a kinase-independent mechanism. EMBO J. 21: 1327–1338.
  • Toda, T., I. Uno, T. Ishikawa, S. Powers, T. Kataoka, D. Broek, S. Cameron, J. Broach, K. Matsumoto, and M. Wigler. 1985. In yeast, RAS proteins are controlling elements of adenylate cyclase. Cell 40: 27–36.
  • Urano, T., R. Emkey, and L. A. Feig. 1996. Ral-GTPases mediate a distinct downstream signaling pathway from Ras that facilitates cellular transformation. EMBO J. 15: 810–816.
  • Vojtek, A. B., S. M. Hollenberg, and J. A. Cooper. 1993. Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell 74: 205–214.
  • Voss, M., P. A. O. Weernink, S. Haupenthal, U. Moller, R. H. Cool, B. Bauer, J. H. Camonis, K. H. Jakobs, and M. Schmidt. 1999. Phospholipase D stimulation by receptor tyrosine kinases mediated by protein kinase C and a Ras/Ral signaling cascade. J. Biol. Chem. 274: 34691–34698.
  • Vossler, M. R., H. Yao, R. D. York, M. G. Pan, C. S. Rim, and P. J. Stork. 1997. cAMP activates MAP kinase and Elk-1 through a B-Raf- and Rap1-dependent pathway. Cell 89: 73–82.
  • Walhout, A. J. M., R. Sordella, X. Lu, J. L. Hartley, G. F. Temple, M. A. Brasch, N. Thierry-Mieg, and M. Vidal. 2000. Protein interaction mapping in C. elegans using proteins involved in vulval development. Science 287: 116–122.
  • Wang, K. L., and B. D. Roufogalis. 1999. Ca2+/calmodulin stimulates GTP binding to the ras-related protein ral-A. J. Biol. Chem. 274: 14525–14528.
  • Ward, Y., W. Wang, E. Woodhouse, I. Linnoila, L. Liotta, and K. Kelly. 2001. Signal pathways which promote invasion and metastasis: critical and distinct contributions of extracellular signal-regulated kinase and ral-specific guanine exchange factor pathways. Mol. Cell. Biol. 21: 5958–5969.
  • Weinkove, D., T. P. Neufeld, T. Twardzik, M. D. Waterfield, and S. J. Leevers. 1999. Regulation of imaginal disc cell size, cell number and organ size by Drosophila class I(A) phosphoinositide 3-kinase and its adaptor. Curr. Biol. 9: 1019–1029.
  • Wheeler, D. L., D. M. Church, A. E. Lash, D. D. Leipe, T. L. Madden, J. U. Pontius, G. D. Schuler, L. M. Schriml, T. A. Tatusova, L. Wagner, and B. A. Rapp. 2002. Database resources of the National Center for Biotechnology Information: 2002 update. Nucleic Acids Res. 30: 13–16.
  • 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.
  • White, M. A., T. Vale, J. H. Camonis, E. Schaefer, and M. H. Wigler. 1996. A role for Ral guanine nucleotide dissociation stimulator in mediating Ras-induced transformation. J. Biol. Chem. 271: 16439–16442.
  • Wieschaus, E., and C. Nüsslein-Volhard. 1998. Looking at embryos, p. 179–214. In D. B. Roberts (ed.), Drosophila, a practical approach, 2nd ed., vol. 191. IRL Press, Oxford, United Kingdom.
  • Wittinghofer, A., and C. Herrmann. 1995. Ras-effector interactions, the problem of specificity. FEBS Lett. 369: 52–56.
  • Wolthuis, R. M., and J. L. Bos. 1999. Ras caught in another affair: the exchange factors for Ral. Curr. Opin. Genet. Dev. 9: 112–117.
  • Wolthuis, R. M., N. D. 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.
  • Wolthuis, R. M., B. Franke, M. van Triest, B. Bauer, R. H. Cool, J. H. Camonis, J. W. Akkerman, and J. L. Bos. 1998. Activation of the small GTPase Ral in platelets. Mol. Cell. Biol. 18: 2486–2491.
  • Yaffe, M. B., G. G. Leparc, J. Lai, T. Obata, S. Volinia, and L. C. Cantley. 2001. A motif-based profile scanning approach for genome-wide prediction of signaling pathways. Nat. Biotechnol. 19: 348–353.
  • Zhao, Z., and S. A. Rivkees. 2000. Tissue-specific expression of GTPas RalA and RalB during embryogenesis and regulation by epithelial-mesenchymal interaction. Mech. Dev. 97: 201–204.
  • Zhu, J., Y. Qin, M. Zhao, L. Van Aelst, and R. Malinow. 2002. Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell 110: 443–455.
  • Zwartkruis, F. J., R. M. Wolthuis, N. M. Nabben, B. Franke, and J. L. Bos. 1998. Extracellular signal-regulated activation of Rap1 fails to interfere in Ras effector signalling. EMBO J. 17: 5905–5912.

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