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Gene Review

Rala  -  v-ral simian leukemia viral oncogene...

Mus musculus

Synonyms: 3010001O15Rik, AW322615, Ral, Ral-a, Ras-related protein Ral-A, ...
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Disease relevance of Rala


High impact information on Rala

  • Thus RalA is involved in the tyrosine kinase activation of PLD through its unique N terminus, and that PLD is a downstream target of a Ras/Ral GTPase cascade [5].
  • This Ral-mediated, JNK-dependent phosphorylation is involved in the nuclear translocation and transcriptional activation of FOXO4 after H2O2 treatment [6].
  • The results reported here, therefore, outline a homeostasis mechanism for sustaining cellular reactive oxygen species that is controlled by signalling pathways that can convey both negative (PI-3K/PKB) and positive (Ras/Ral) inputs [6].
  • Rlf, when targeted to the plasma membrane using the Ras farnesyl attachment site (Rlf-CAAX), is constitutively active, inducing both Ral activation and c-fos promoter activity [7].
  • From three known effectors which retain the ability to interact with Ras(V12G37), overexpression of phospholipase C epsilon but not that of RIN1 or Ral guanine nucleotide exchange factors enhanced cytokine and nuclear factor-activated T cell reporter T cell responses [8].

Chemical compound and disease context of Rala


Biological context of Rala

  • To further delineate R-Ras downstream signaling events, we observed that while a dominant negative mutant of Akt/protein kinase inhibited the ability of R-Ras to promote cell survival, both dominant negative mutants of Rac and Ral suppressed cell adhesion stimulated by R-Ras [10].
  • To investigate if Ral GTPases play a role in development, temporal and spatial patterns of RalA and RalB gene expression were examined during embryogenesis [11].
  • From these results we conclude that Ral-mediated phosphorylation of threonines 447 and 451 is required for proper activity of AFX-WT [12].
  • Furthermore, inhibition of Ral-GEF activity by expression of a dominant negative Ral mutant accelerated cell cycle arrest and enhanced neurite outgrowth in response to NGF treatment [13].
  • RalBP1 is a potential effector protein of small GTP-binding protein Ral and regulates endocytosis of epidermal growth factor and insulin receptors [14].

Anatomical context of Rala

  • We show that inhibition of Ral signaling blocks DNA synthesis in human tumor cell lines containing activating mutations in TC21, demonstrating for the first time that this pathway is required for the proliferation of human tumor cells [15].
  • In contrast, the addition of recombinant Ral proteins (RalA and RalB), glucosylation substrates for TscL and TcdB-1470, but not for TcdB, to membranes of TcdB-1470- or TcsL-treated cells fully restored PLD stimulation by PMA without altering the strict MgATP dependence of PMA-induced PLD stimulation [16].
  • In addition, retrovirus-mediated expression of dominant-negative versions of Ras and Ral led to a reduced migration of transplanted myoblasts in vivo [17].
  • Ral-GTPase influences the regulation of the readily releasable pool of synaptic vesicles [18].
  • Involvement of Ras and Ral in chemotactic migration of skeletal myoblasts [19].

Associations of Rala with chemical compounds

  • Finally, Ral-GDS belongs to a family of guanine nucleotide exchange factors that activate Ral GTPases [20].
  • When cultured with 1 microM raloxifene, MCF-7/Ral cells grew statistically significantly (P<.001) faster than MCF-7 cells [9].
  • Treatment with either raloxifene or tamoxifen stimulated MCF-7/Ral tumor growth, suggesting that such tumors were resistant to both drugs [9].

Physical interactions of Rala

  • Moreover, we have identified that the COOH-terminal region of ARIP2 interacts with Ral-binding protein 1 (RalBP1) [14].

Regulatory relationships of Rala


Other interactions of Rala


Analytical, diagnostic and therapeutic context of Rala


  1. Signal pathways which promote invasion and metastasis: critical and distinct contributions of extracellular signal-regulated kinase and Ral-specific guanine exchange factor pathways. Ward, Y., Wang, W., Woodhouse, E., Linnoila, I., Liotta, L., Kelly, K. Mol. Cell. Biol. (2001) [Pubmed]
  2. pH-enhanced cytopathic effects of Clostridium sordellii lethal toxin. Qa'Dan, M., Spyres, L.M., Ballard, J.D. Infect. Immun. (2001) [Pubmed]
  3. p130Cas regulates the activity of AND-34, a novel Ral, Rap1, and R-Ras guanine nucleotide exchange factor. Gotoh, T., Cai, D., Tian, X., Feig, L.A., Lerner, A. J. Biol. Chem. (2000) [Pubmed]
  4. JAK/STAT3-dependent activation of the RalGDS/Ral pathway in M1 mouse myeloid leukemia cells. Senga, T., Iwamoto, T., Kitamura, T., Miyake, Y., Hamaguchi, M. J. Biol. Chem. (2001) [Pubmed]
  5. Involvement of Ral GTPase in v-Src-induced phospholipase D activation. Jiang, H., Luo, J.Q., Urano, T., Frankel, P., Lu, Z., Foster, D.A., Feig, L.A. Nature (1995) [Pubmed]
  6. FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK. Essers, M.A., Weijzen, S., de Vries-Smits, A.M., Saarloos, I., de Ruiter, N.D., Bos, J.L., Burgering, B.M. EMBO J. (2004) [Pubmed]
  7. Stimulation of gene induction and cell growth by the Ras effector Rlf. Wolthuis, R.M., de Ruiter, N.D., Cool, R.H., Bos, J.L. EMBO J. (1997) [Pubmed]
  8. Activation of CD4 T cells by Raf-independent effectors of Ras. Czyzyk, J., Brogdon, J.L., Badou, A., Henegariu, O., Preston Hurlburt, P., Flavell, R., Bottomly, K. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  9. Apoptotic action of 17beta-estradiol in raloxifene-resistant MCF-7 cells in vitro and in vivo. Liu, H., Lee, E.S., Gajdos, C., Pearce, S.T., Chen, B., Osipo, C., Loweth, J., McKian, K., De Los Reyes, A., Wing, L., Jordan, V.C. J. Natl. Cancer Inst. (2003) [Pubmed]
  10. Differential roles of Akt, Rac, and Ral in R-Ras-mediated cellular transformation, adhesion, and survival. Osada, M., Tolkacheva, T., Li, W., Chan, T.O., Tsichlis, P.N., Saez, R., Kimmelman, A.C., Chan, A.M. Mol. Cell. Biol. (1999) [Pubmed]
  11. Tissue-specific expression of GTPas RalA and RalB during embryogenesis and regulation by epithelial-mesenchymal interaction. Zhao, Z., Rivkees, S.A. Mech. Dev. (2000) [Pubmed]
  12. Regulation of the Forkhead transcription factor AFX by Ral-dependent phosphorylation of threonines 447 and 451. De Ruiter, N.D., Burgering, B.M., Bos, J.L. Mol. Cell. Biol. (2001) [Pubmed]
  13. Ral-specific guanine nucleotide exchange factor activity opposes other Ras effectors in PC12 cells by inhibiting neurite outgrowth. Goi, T., Rusanescu, G., Urano, T., Feig, L.A. Mol. Cell. Biol. (1999) [Pubmed]
  14. Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent pathway. Matsuzaki, T., Hanai, S., Kishi, H., Liu, Z., Bao, Y., Kikuchi, A., Tsuchida, K., Sugino, H. J. Biol. Chem. (2002) [Pubmed]
  15. Activation of the Ral and phosphatidylinositol 3' kinase signaling pathways by the ras-related protein TC21. Rosário, M., Paterson, H.F., Marshall, C.J. Mol. Cell. Biol. (2001) [Pubmed]
  16. Specific inhibition of phorbol ester-stimulated phospholipase D by Clostridium sordellii lethal toxin and Clostridium difficile toxin B-1470 in HEK-293 cells. Restoration by Ral GTPases. Schmidt, M., Voss, M., Thiel, M., Bauer, B., Grannass, A., Tapp, E., Cool, R.H., de Gunzburg, J., von Eichel-Streiber, C., Jakobs, K.H. J. Biol. Chem. (1998) [Pubmed]
  17. Reduced mobility of fibroblast growth factor (FGF)-deficient myoblasts might contribute to dystrophic changes in the musculature of FGF2/FGF6/mdx triple-mutant mice. Neuhaus, P., Oustanina, S., Loch, T., Krüger, M., Bober, E., Dono, R., Zeller, R., Braun, T. Mol. Cell. Biol. (2003) [Pubmed]
  18. Ral-GTPase influences the regulation of the readily releasable pool of synaptic vesicles. Polzin, A., Shipitsin, M., Goi, T., Feig, L.A., Turner, T.J. Mol. Cell. Biol. (2002) [Pubmed]
  19. Involvement of Ras and Ral in chemotactic migration of skeletal myoblasts. Suzuki, J., Yamazaki, Y., Li, G., Kaziro, Y., Koide, H., Guang, L. Mol. Cell. Biol. (2000) [Pubmed]
  20. Modulation of phospholipase D by Ras proteins mediated by its effectors Ral-GDS, PI3K and Raf-1. Lucas, L., Penalva, V., Ramírez de Molina, A., Del Peso, L., Lacal, J.C. Int. J. Oncol. (2002) [Pubmed]
  21. The G alpha(o/i)-coupled cannabinoid receptor-mediated neurite outgrowth involves Rap regulation of Src and Stat3. He, J.C., Gomes, I., Nguyen, T., Jayaram, G., Ram, P.T., Devi, L.A., Iyengar, R. J. Biol. Chem. (2005) [Pubmed]
  22. Pathway- and expression level-dependent effects of oncogenic N-Ras: p27(Kip1) mislocalization by the Ral-GEF pathway and Erk-mediated interference with Smad signaling. Kfir, S., Ehrlich, M., Goldshmid, A., Liu, X., Kloog, Y., Henis, Y.I. Mol. Cell. Biol. (2005) [Pubmed]
  23. Synergistic activation of c-fos promoter activity by Raf and Ral GDP dissociation stimulator. Okazaki, M., Kishida, S., Hinoi, T., Hasegawa, T., Tamada, M., Kataoka, T., Kikuchi, A. Oncogene (1997) [Pubmed]
  24. Structure of the GTPase-binding domain of Sec5 and elucidation of its Ral binding site. Mott, H.R., Nietlispach, D., Hopkins, L.J., Mirey, G., Camonis, J.H., Owen, D. J. Biol. Chem. (2003) [Pubmed]
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