Inhibition of GTPase activating protein stimulation of Ras-p21 GTPase by the Krev-1 gene product - PubMed (original) (raw)
. 1990 Jul 13;249(4965):169-71.
doi: 10.1126/science.2164710.
Affiliations
- PMID: 2164710
- DOI: 10.1126/science.2164710
Inhibition of GTPase activating protein stimulation of Ras-p21 GTPase by the Krev-1 gene product
M Frech et al. Science. 1990.
Abstract
Krev-1 is known to suppress transformation by ras. However, the mechanism of the suppression is unclear. The protein product of Krev-1, Rap1A-p21, is identical to Ras-p21 proteins in the region where interaction with guanosine triphosphatase (GTPase) activating protein (GAP) is believed to occur. Therefore, the ability of GAP to interact with Rap1A-p21 was tested. Rap1A-p21 was not activated by GAP but bound tightly to GAP and was an effective competitive inhibitor of GAP-mediated Ras-GTPase activity. Binding of GAP to Rap1A-p21 was strictly guanosine triphosphate (GTP)-dependent. The ability of Rap1A-p21 to bind tightly to GAP may account for Krev-1 suppression of transformation by ras. This may occur by preventing interaction of GAP with Ras-p21 or with other cellular proteins necessary for GAP-mediated Ras GTPase activity.
Similar articles
- Amino acid 61 is a determinant of sensitivity of rap proteins to the ras GTPase activating protein.
Hart PA, Marshall CJ. Hart PA, et al. Oncogene. 1990 Jul;5(7):1099-101. Oncogene. 1990. PMID: 2115644 - Biochemical characterization of baculovirus-expressed rap1A/Krev-1 and its regulation by GTPase-activating proteins.
Quilliam LA, Der CJ, Clark R, O'Rourke EC, Zhang K, McCormick F, Bokoch GM. Quilliam LA, et al. Mol Cell Biol. 1990 Jun;10(6):2901-8. doi: 10.1128/mcb.10.6.2901-2908.1990. Mol Cell Biol. 1990. PMID: 2160589 Free PMC article. - Guanosine triphosphatase activating protein (GAP) interacts with the p21 ras effector binding domain.
Adari H, Lowy DR, Willumsen BM, Der CJ, McCormick F. Adari H, et al. Science. 1988 Apr 22;240(4851):518-21. doi: 10.1126/science.2833817. Science. 1988. PMID: 2833817 - ras GTPase activating protein: signal transmitter and signal terminator.
McCormick F. McCormick F. Cell. 1989 Jan 13;56(1):5-8. doi: 10.1016/0092-8674(89)90976-8. Cell. 1989. PMID: 2535967 Review. - The kinetic mechanism of the GAP-activated GTPase of p21 ras.
Moore KJ, Lowe PN, Eccleston JF. Moore KJ, et al. Philos Trans R Soc Lond B Biol Sci. 1992 Apr 29;336(1276):49-53; discussion 53-4. doi: 10.1098/rstb.1992.0043. Philos Trans R Soc Lond B Biol Sci. 1992. PMID: 1351296 Review.
Cited by
- Cellular ras gene activity is required for full neoplastic transformation by polyomavirus.
Raptis L, Marcellus R, Corbley MJ, Krook A, Whitfield J, Anderson SK, Haliotis T. Raptis L, et al. J Virol. 1991 Oct;65(10):5203-10. doi: 10.1128/JVI.65.10.5203-5210.1991. J Virol. 1991. PMID: 1654439 Free PMC article. - Role of rap1B and p21ras GTPase-activating protein in the regulation of phospholipase C-gamma 1 in human platelets.
Torti M, Lapetina EG. Torti M, et al. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7796-800. doi: 10.1073/pnas.89.16.7796. Proc Natl Acad Sci U S A. 1992. PMID: 1323853 Free PMC article. - R-Ras3/M-Ras induces neuronal differentiation of PC12 cells through cell-type-specific activation of the mitogen-activated protein kinase cascade.
Kimmelman AC, Nuñez Rodriguez N, Chan AM. Kimmelman AC, et al. Mol Cell Biol. 2002 Aug;22(16):5946-61. doi: 10.1128/MCB.22.16.5946-5961.2002. Mol Cell Biol. 2002. PMID: 12138204 Free PMC article. - Common Patterns of Hydrolysis Initiation in P-loop Fold Nucleoside Triphosphatases.
Kozlova MI, Shalaeva DN, Dibrova DV, Mulkidjanian AY. Kozlova MI, et al. Biomolecules. 2022 Sep 22;12(10):1345. doi: 10.3390/biom12101345. Biomolecules. 2022. PMID: 36291554 Free PMC article. - Mutational and kinetic analyses of the GTPase-activating protein (GAP)-p21 interaction: the C-terminal domain of GAP is not sufficient for full activity.
Gideon P, John J, Frech M, Lautwein A, Clark R, Scheffler JE, Wittinghofer A. Gideon P, et al. Mol Cell Biol. 1992 May;12(5):2050-6. doi: 10.1128/mcb.12.5.2050-2056.1992. Mol Cell Biol. 1992. PMID: 1569940 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous