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 Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bouton, A H Articles by Parsons, J T Search for Related Content PubMed PubMed Citation Articles by Bouton, A H Articles by Parsons, J T

Transformation by pp60src or stimulation of cells with epidermal growth factor induces the stable association of tyrosine-phosphorylated cellular proteins with GTPase-activating protein.

Department of Microbiology and Cancer Center, University of Virginia Health Sciences Center, Charlottesville 22908.

ABSTRACT

GTPase-activating protein (GAP) is a cytosolic protein that stimulates the rate of hydrolysis of GTP (GTP to GDP) bound to normal p21ras, but does not catalyze the hydrolysis of GTP bound to oncogenic, activated forms of the ras protein. Transformation of cells with v-src or activated transforming variants of c-src or stimulation of cells with epidermal growth factor resulted in the stable association of GAP with two tyrosine-phosphorylated cellular proteins of 64 kDa (p64) and 190 kDa (p190). Analysis of GAP immune complexes isolated from extracts of metabolically labeled src-transformed cells and epidermal growth factor-stimulated cells indicated that tyrosine phosphorylation of p64 and p190 appeared to be coincident with the stable association of these proteins with GAP. Quantitation of the amount of p64 associated with GAP in v-src-transformed cells, however, indicated that only 15 to 25% of tyrosine-phosphorylated p64 was found in complex with GAP. Mutations within the SH2 region of pp60src that render activated pp60src defective for transformation inhibited the efficient formation of complexes between GAP and the tyrosine-phosphorylated forms of p64 and p190. From these data, we suggest that tyrosine phosphorylation and stable association of p64 with GAP is an important step in mediating cellular signaling through the p21ras-GAP pathway.

This article has been cited by other articles:

• Holinstat, M., Knezevic, N., Broman, M., Samarel, A. M., Malik, A. B., Mehta, D. (2006). Suppression of RhoA Activity by Focal Adhesion Kinase-induced Activation of p190RhoGAP: ROLE IN REGULATION OF ENDOTHELIAL PERMEABILITY. J. Biol. Chem. 281: 2296-2305 [Abstract] [Full Text]  
• Tu, S., Wu, W. J., Wang, J., Cerione, R. A. (2003). Epidermal Growth Factor-dependent Regulation of Cdc42 Is Mediated by the Src Tyrosine Kinase. J. Biol. Chem. 278: 49293-49300 [Abstract] [Full Text]  
• Martelli, M. P., Boomer, J., Bu, M., Bierer, B. E. (2001). T Cell Regulation of p62dok (Dok1) Association with Crk-L. J. Biol. Chem. 276: 45654-45661 [Abstract] [Full Text]  
• 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]  
• Haskell, M., Nickles, A., Agati, J., Su, L, Dukes, B., Parsons, S. (2001). Phosphorylation of p190 on Tyr1105 by c-Src is necessary but not sufficient for EGF-induced actin disassembly in C3H10T1/2 fibroblasts. J. Cell Sci. 114: 1699-1708 [Abstract]  
• CHEN, W.-T., WANG, J.-Y. (1999). Specialized Surface Protrusions of Invasive Cells, Invadopodia and Lamellipodia, Have Differential MT1-MMP, MMP-2, and TIMP-2 Localization. Ann. N. Y. Acad. Sci. 878: 361-371 [Abstract] [Full Text]  
• Roof, R. W., Haskell, M. D., Dukes, B. D., Sherman, N., Kinter, M., Parsons, S. J. (1998). Phosphotyrosine (p-Tyr)-Dependent and -Independent Mechanisms of p190 RhoGAP-p120 RasGAP Interaction: Tyr 1105 of p190, a Substrate for c-Src, Is the Sole p-Tyr Mediator of Complex Formation. Mol. Cell. Biol. 18: 7052-7063 [Abstract] [Full Text]  
• Nakahara, H., Mueller, S. C., Nomizu, M., Yamada, Y., Yeh, Y., Chen, W.-T. (1998). Activation of beta 1 Integrin Signaling Stimulates Tyrosine Phosphorylation of p190RhoGAP and Membrane-protrusive Activities at Invadopodia. J. Biol. Chem. 273: 9-12 [Abstract] [Full Text]  
• Liu, M., Qin, Y., Liu, J., Tanswell, A. K., Post, M. (1996). Mechanical Strain Induces pp60[IMAGE] Activation and Translocation to Cytoskeleton in Fetal Rat Lung Cells. J. Biol. Chem. 271: 7066-7071 [Abstract] [Full Text]  
• Aaronson, S. (1991). Growth factors and cancer. Science 254: 1146-1153 [Abstract]  
• Koch, C., Anderson, D, Moran, M., Ellis, C, Pawson, T (1991). SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science 252: 668-674 [Abstract]  
• Sattler, M., Verma, S., Pride, Y. B., Salgia, R., Rohrschneider, L. R., Griffin, J. D. (2001). SHIP1, an SH2 Domain Containing Polyinositol-5-phosphatase, Regulates Migration through Two Critical Tyrosine Residues and Forms a Novel Signaling Complex with DOK1 and CRKL. J. Biol. Chem. 276: 2451-2458 [Abstract] [Full Text]