Inhibition of v-src-induced transformation by a GTPase-activating protein
- PMID: 2017178
- PMCID: PMC360061
- DOI: 10.1128/mcb.11.5.2812-2818.1991
Inhibition of v-src-induced transformation by a GTPase-activating protein
Abstract
Previous work has shown that microinjection into cells of antibodies against p21ras blocks transformation by src, suggesting that oncogenic transformation by pp60v-src is dependent on p21ras. The activity of p21ras itself is regulated by its cyclic association with GDP-GTP, where p21ras-GTP is the active form and p21ras-GDP is the inactive form. A GTPase-activating protein (GAP) mediates the inactivation of p21ras by facilitating the conversion of the active p21ras-GTP to the inactive p21ras-GDP. This predicts that overexpression of GAP would inactivate p21ras and block transformation of cells by src. In this paper, we confirm this prediction. We report that overexpression of GAP in NIH 3T3 cells blocks transformation by pp60v-src but not by v-ras. Susceptibility to transformation by v-src is restored when GAP expression is lowered to levels comparable to that in control cells. These results support the suggestion that p21ras plays a central role in the signalling pathway used by pp60v-src.
Similar articles
-
Suppression of src transformation by overexpression of full-length GTPase-activating protein (GAP) or of the GAP C terminus.Mol Cell Biol. 1991 May;11(5):2819-25. doi: 10.1128/mcb.11.5.2819-2825.1991. Mol Cell Biol. 1991. PMID: 2017179 Free PMC article.
-
Functional role of GTPase-activating protein in cell transformation by pp60v-src.Mol Cell Biol. 1993 Nov;13(11):6799-809. doi: 10.1128/mcb.13.11.6799-6809.1993. Mol Cell Biol. 1993. PMID: 7692232 Free PMC article.
-
Transformation by pp60src or stimulation of cells with epidermal growth factor induces the stable association of tyrosine-phosphorylated cellular proteins with GTPase-activating protein.Mol Cell Biol. 1991 Feb;11(2):945-53. doi: 10.1128/mcb.11.2.945-953.1991. Mol Cell Biol. 1991. PMID: 1703633 Free PMC article.
-
Fluorescence approaches to the study of the p21ras GTPase mechanism.Biochem Soc Trans. 1991 Apr;19(2):432-7. doi: 10.1042/bst0190432. Biochem Soc Trans. 1991. PMID: 1889625 Review.
-
Role of GTPases and GTPase regulatory proteins in oncogenesis.Crit Rev Oncog. 1993;4(4):389-402. Crit Rev Oncog. 1993. PMID: 8353139 Review.
Cited by
-
Ras-GAP controls Rho-mediated cytoskeletal reorganization through its SH3 domain.Mol Cell Biol. 1998 Sep;18(9):5567-78. doi: 10.1128/MCB.18.9.5567. Mol Cell Biol. 1998. PMID: 9710640 Free PMC article.
-
Muscarinic receptors transform NIH 3T3 cells through a Ras-dependent signalling pathway inhibited by the Ras-GTPase-activating protein SH3 domain.Mol Cell Biol. 1994 Dec;14(12):7943-52. doi: 10.1128/mcb.14.12.7943-7952.1994. Mol Cell Biol. 1994. PMID: 7969134 Free PMC article.
-
Ras-independent transformation by v-Src.Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3028-33. doi: 10.1073/pnas.94.7.3028. Proc Natl Acad Sci U S A. 1997. PMID: 9096340 Free PMC article.
-
Regulation of the junB gene by v-src.Mol Cell Biol. 1992 Aug;12(8):3356-64. doi: 10.1128/mcb.12.8.3356-3364.1992. Mol Cell Biol. 1992. PMID: 1630451 Free PMC article.
-
Differential modulation of plasminogen activator gene expression by oncogene-encoded protein tyrosine kinases.Mol Cell Biol. 1993 Sep;13(9):5888-97. doi: 10.1128/mcb.13.9.5888-5897.1993. Mol Cell Biol. 1993. PMID: 7689154 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous