This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by DeClue, J E Articles by Lowy, D R Search for Related Content PubMed PubMed Citation Articles by DeClue, J E Articles by Lowy, D R

 Previous Article  |  Next Article 

Mol Cell Biol. 1993 November; 13(11): 6799-6809

Functional role of GTPase-activating protein in cell transformation by pp60v-src.

Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland 20892.

ABSTRACT

Morphological transformation of NIH 3T3 cells was observed following coexpression of a portion of the ras GTPase-activating protein (GAP) comprising the amino terminus (GAP-N) and a mutant of v-src (MDSRC) lacking the membrane-localizing sequence. Cells expressing either of these genes alone remained nontransformed. Coexpression of GAP-N with MDSRC did not alter the subcellular localization, kinase activity, or pattern of cellular substrates phosphorylated by the MDSRC product. In contrast to SHC, phospholipase C-gamma 1, and the p85 alpha phosphatidylinositol 3'-kinase subunit, the endogenous GAP product (p120GAP) was highly tyrosine-phosphorylated only in cells transformed by wild-type v-src. Furthermore, for transformation induced by wild-type v-src as well as by coexpression of MDSRC and GAP-N, a strict correlation was observed between cell transformation, elevated tyrosine phosphorylation of p62, p190, and a novel protein of 150 kDa, and complex formation between these proteins and p120GAP. As with cells transformed by wild-type v-src, the MDSRC plus GAP-N transformants remained dependent on endogenous Ras. The results suggest that tyrosine phosphorylation and complex formation involving p120GAP represent critical elements of cell transformation by v-src and that complementation of the cytosolic v-src mutant by GAP-N results, at least in part, from the formation of these complexes.

This article has been cited by other articles:

• Hosooka, T., Noguchi, T., Nagai, H., Horikawa, T., Matozaki, T., Ichihashi, M., Kasuga, M. (2001). Inhibition of the Motility and Growth of B16F10 Mouse Melanoma Cells by Dominant Negative Mutants of Dok-1. Mol. Cell. Biol. 21: 5437-5446 [Abstract] [Full Text]  
• Zhao, M., Schmitz, A. A.P., Qin, Y., Di Cristofano, A., Pandolfi, P. P., Van Aelst, L. (2001). Phosphoinositide 3-Kinase-dependent Membrane Recruitment of p62dok Is Essential for Its Negative Effect on Mitogen-activated Protein (MAP) Kinase Activation. J. Exp. Med. 194: 265-274 [Abstract] [Full Text]  
• Di Cristofano, A., Niki, M., Zhao, M., Karnell, F. G., Clarkson, B., Pear, W. S., Van Aelst, L., Pandolfi, P. P. (2001). p62dok, a Negative Regulator of Ras and Mitogen-activated Protein Kinase (MAPK) Activity, Opposes Leukemogenesis by p210bcr-abl. J. Exp. Med. 194: 275-284 [Abstract] [Full Text]  
• Cong, F., Yuan, B., Goff, S. P. (1999). Characterization of a Novel Member of the DOK Family That Binds and Modulates Abl Signaling. Mol. Cell. Biol. 19: 8314-8325 [Abstract] [Full Text]  
• Yang, W.-C., Ghiotto, M., Barbarat, B., Olive, D. (1999). The Role of Tec Protein-tyrosine Kinase in T Cell Signaling. J. Biol. Chem. 274: 607-617 [Abstract] [Full Text]  
• Abdellatif, M., Packer, S. E., Michael, L. H., Zhang, D., Charng, M. J., Schneider, M. D. (1998). A Ras-Dependent Pathway Regulates RNA Polymerase II Phosphorylation in Cardiac Myocytes: Implications for Cardiac Hypertrophy. Mol. Cell. Biol. 18: 6729-6736 [Abstract] [Full Text]  
• Sturtevant, M. A., O'Neill, J. W., Bier, E. (1994). Down-regulation of Drosophila Egf-r mRNA levels following hyperactivated receptor signaling. Development 120: 2593-2600 [Abstract]  
• Trentin, G. A., Yin, X., Tahir, S., Lhotak, S., Farhang-Fallah, J., Li, Y., Rozakis-Adcock, M. (2001). A Mouse Homologue of the Drosophila Tumor Suppressor l(2)tid Gene Defines a Novel Ras GTPase-activating Protein (RasGAP)-binding Protein. J. Biol. Chem. 276: 13087-13095 [Abstract] [Full Text]