Ral-GTPases mediate a distinct downstream signaling pathway from Ras that facilitates cellular transformation - PubMed (original) (raw)
. 1996 Feb 15;15(4):810-6.
Affiliations
- PMID: 8631302
- PMCID: PMC450279
Ral-GTPases mediate a distinct downstream signaling pathway from Ras that facilitates cellular transformation
T Urano et al. EMBO J. 1996.
Abstract
Ral proteins (RalA and RalB) comprise a distinct family of Ras-related GTPases (Feig and Emkey, 1993). Recently, Ral-GDS, the exchange factor that activates Ral proteins, has been shown to bind specifically to the activated forms of RasH, R-Ras and Rap1A, in the yeast two-hybrid system. Here we demonstrate that although all three GTPases have the capacity to bind Ral-GDS in mammalian cells, only RasH activates Ral-GDS. Furthermore, although constitutively activated Ra1A does not induce oncogenic transformation on its own, its expression enhances the transforming activities of both RasH and Raf. Finally, a dominant inhibitory form of RalA suppresses the transforming activities of both RasH and Raf. These results demonstrate that activation of Ral-GDS and thus its target, Ral, constitutes a distinct downstream signaling pathway from RasH that potentiates oncogenic transformation.
Similar articles
- 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 JC. Lucas L, et al. Int J Oncol. 2002 Sep;21(3):477-85. Int J Oncol. 2002. PMID: 12168089 - Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation.
Khosravi-Far R, Solski PA, Clark GJ, Kinch MS, Der CJ. Khosravi-Far R, et al. Mol Cell Biol. 1995 Nov;15(11):6443-53. doi: 10.1128/MCB.15.11.6443. Mol Cell Biol. 1995. PMID: 7565796 Free PMC article. - Ras target proteins in eukaryotic cells.
Marshall MS. Marshall MS. FASEB J. 1995 Oct;9(13):1311-8. doi: 10.1096/fasebj.9.13.7557021. FASEB J. 1995. PMID: 7557021 Review. - Signaling molecules that mediate the actions of FGF.
Demo SD, Kikuchi A, Peters KG, MacNicol AM, Muslin AJ, Williams LT. Demo SD, et al. Princess Takamatsu Symp. 1994;24:243-9. Princess Takamatsu Symp. 1994. PMID: 8983079 Review.
Cited by
- Structure characterization of human RalGDS gene, and the identification of its novel variant.
Zheng Q, Yu L, Zhao Y, Zhang H, Fu Q, Mao N, Hu P, Geng Z, Zhao S. Zheng Q, et al. Mol Biol Rep. 2000;27(4):209-16. doi: 10.1023/a:1011043122220. Mol Biol Rep. 2000. PMID: 11455956 - Cellular response to oncogenic ras involves induction of the Cdk4 and Cdk6 inhibitor p15(INK4b).
Malumbres M, Pérez De Castro I, Hernández MI, Jiménez M, Corral T, Pellicer A. Malumbres M, et al. Mol Cell Biol. 2000 Apr;20(8):2915-25. doi: 10.1128/MCB.20.8.2915-2925.2000. Mol Cell Biol. 2000. PMID: 10733595 Free PMC article. - PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma.
Sittewelle M, Kappès V, Zhou C, Lécuyer D, Monsoro-Burq AH. Sittewelle M, et al. Life Sci Alliance. 2022 Aug 1;5(12):e202201377. doi: 10.26508/lsa.202201377. Life Sci Alliance. 2022. PMID: 35914811 Free PMC article. - Cdc42 regulates anchorage-independent growth and is necessary for Ras transformation.
Qiu RG, Abo A, McCormick F, Symons M. Qiu RG, et al. Mol Cell Biol. 1997 Jun;17(6):3449-58. doi: 10.1128/MCB.17.6.3449. Mol Cell Biol. 1997. PMID: 9154844 Free PMC article.
References
- Proc Natl Acad Sci U S A. 1986 Jul;83(13):4607-11 - PubMed
- Nature. 1995 Aug 10;376(6540):524-7 - PubMed
- FEBS Lett. 1990 Jan 15;260(1):48-52 - PubMed
- J Biol Chem. 1990 Apr 15;265(11):6353-9 - PubMed
- J Biol Chem. 1991 May 25;266(15):9703-6 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous