Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 22 January 1993:
Vol. 259. no. 5094, pp. 525 - 528
DOI: 10.1126/science.7678707
Prev | Table of Contents | Next

Articles

Science, Vol 259, Issue 5094, 525-528
Copyright © 1993 by American Association for the Advancement of Science

articles

Identification of the SH3 domain of GAP as an essential sequence for Ras-GAP-mediated signaling

M Duchesne, F Schweighoffer, F Parker, F Clerc, Y Frobert, MN Thang, and B Tocque

Rhone Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry Sur Seine, France.

Guanosine triphosphatase activating protein (GAP) is an essential component of Ras signaling pathways. GAP functions in different cell types as a deactivator and a transmitter of cellular Ras signals. A domain (amino acids 275 to 351) encompassing the Src homology region 3 (SH3) of GAP was found to be essential for GAP signaling. A monoclonal antibody was used to block germinal vesicle breakdown (GVBD) induced by the oncogenic protein Ha-ras Lys12 in Xenopus oocytes. The monoclonal antibody, which was found to recognize the peptide containing amino acids 275 to 351 within the amino-terminal domain of GAP, did not modify the stimulation of the Ha-Ras-GTPase by GAP. Injection of peptides corresponding to amino acids 275 to 351 and 317 to 326 blocked GVBD induced by insulin or by Ha-Ras Lys12 but not that induced by progesterone. These findings confirm that GAP is an effector for Ras in Xenopus oocytes and that the SH3 domain is essential for signal transduction.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A Human CD4 Monoclonal Antibody for the Treatment of T-Cell Lymphoma Combines Inhibition of T-Cell Signaling by a Dual Mechanism with Potent Fc-Dependent Effector Activity.
D. A. Rider, C. E.G. Havenith, R. de Ridder, J. Schuurman, C. Favre, J. C. Cooper, S. Walker, O. Baadsgaard, S. Marschner, J. G.J. vandeWinkel, et al. (2007)
Cancer Res. 67, 9945-9953
   Abstract »    Full Text »    PDF »
A Novel Role for Gab1 and SHP2 in Epidermal Growth Factor-induced Ras Activation.
A. Montagner, A. Yart, M. Dance, B. Perret, J.-P. Salles, and P. Raynal (2005)
J. Biol. Chem. 280, 5350-5360
   Abstract »    Full Text »    PDF »
SNT1/FRS2 Mediates Germinal Vesicle Breakdown Induced by an Activated FGF Receptor1 in Xenopus Oocytes.
K. Mood, R. Friesel, and I. O. Daar (2002)
J. Biol. Chem. 277, 33196-33204
   Abstract »    Full Text »    PDF »
The RasGAP N-terminal Fragment Generated by Caspase Cleavage Protects Cells in a Ras/PI3K/Akt-dependent Manner That Does Not Rely on NFkappa B Activation.
J.-Y. Yang and C. Widmann (2002)
J. Biol. Chem. 277, 14641-14646
   Abstract »    Full Text »    PDF »
Heregulin Induces Expression, ATPase Activity, and Nuclear Localization of G3BP, a Ras Signaling Component, in Human Breast Tumors.
C. J. Barnes, F. Li, M. Mandal, Z. Yang, A. A. Sahin, and R. Kumar (2002)
Cancer Res. 62, 1251-1255
   Abstract »    Full Text »    PDF »
Rasputin, the Drosophila homologue of the RasGAP SH3 binding protein, functions in ras- and Rho-mediated signaling.
C Pazman, C. Mayes, M Fanto, S. Haynes, and M Mlodzik (2000)
Development 127, 1715-1725
   Abstract »    PDF »
Cytoskeletal changes induced by GRAF, the GTPase regulator associated with focal adhesion kinase, are mediated by Rho.
J. Taylor, M. Macklem, and J. Parsons (1999)
J. Cell Sci. 112, 231-242
   Abstract »    PDF »
A Ras-Dependent Pathway Regulates RNA Polymerase II Phosphorylation in Cardiac Myocytes: Implications for Cardiac Hypertrophy.
M. Abdellatif, S. E. Packer, L. H. Michael, D. Zhang, M. J. Charng, and M. D. Schneider (1998)
Mol. Cell. Biol. 18, 6729-6736
   Abstract »    Full Text »
Ras-GAP Controls Rho-Mediated Cytoskeletal Reorganization through Its SH3 Domain.
V. Leblanc, B. Tocque, and I. Delumeau (1998)
Mol. Cell. Biol. 18, 5567-5578
   Abstract »    Full Text »
Involvement of Phospholipase C{gamma}1 in Mouse Egg Activation Induced by a Truncated Form of the C-kit Tyrosine Kinase Present in Spermatozoa.
C. Sette, A. Bevilacqua, R. Geremia, and P. Rossi (1998)
J. Cell Biol. 142, 1063-1074
   Abstract »    Full Text »    PDF »
Differential Interactions of the Growth Factor Receptor-bound Protein 2 N-SH3 Domain with Son of Sevenless and Dynamin. POTENTIAL ROLE IN THE Ras-DEPENDENT SIGNALING PATHWAY.
M. Vidal, J.-L. Montiel, D. Cussac, F. Cornille, M. Duchesne, F. Parker, B. Tocque, B.-P. Roques, and C. Garbay (1998)
J. Biol. Chem. 273, 5343-5348
   Abstract »    Full Text »    PDF »
Inhibition of Caenorhabditis elegans vulval induction by gap-1 and by let-23 receptor tyrosine kinase.
A. Hajnal, C. W. Whitfield, and S. K. Kim (1997)
Genes & Dev. 11, 2715-2728
   Abstract »    Full Text »    PDF »
p120 GAP Modulates Ras Activation of Jun Kinases and Transformation.
G. J. Clark, J. K. Westwick, and C. J. Der (1997)
J. Biol. Chem. 272, 1677-1681
   Abstract »    Full Text »    PDF »
The Ca2+-dependent Lipid Binding Domain of P120GAP Mediates Protein-Protein Interactions with Ca2+-dependent Membrane-binding Proteins. EVIDENCE FOR A DIRECT INTERACTION BETWEEN ANNEXIN VI AND P120GAP.
A. J. Davis, J. T. Butt, J. H. Walker, S. E. Moss, and D. J. Gawler (1996)
J. Biol. Chem. 271, 24333-24336
   Abstract »    Full Text »    PDF »
N-terminal Sequences Contained in the Src Homology 2 and 3 Domains of p120 GTPase-activating Protein Are Required for Full Catalytic Activity Toward Ras.
S. S. Bryant, A. L. Mitchell, F. Collins, W. Miao, M. Marshall, and R. Jove (1996)
J. Biol. Chem. 271, 5195-5199
   Abstract »    Full Text »    PDF »
The Ras GTPase-activating Protein (GAP) Is an SH3 Domain-binding Protein and Substrate for the Src-related Tyrosine Kinase, Hck.
S. D. Briggs, S. S. Bryant, R. Jove, S. D. Sanderson, and T. E. Smithgall (1995)
J. Biol. Chem. 270, 14718-14724
   Abstract »    Full Text »    PDF »
SH3 Domains Specifically Regulate Kinase Activity of Expressed Src Family Proteins.
C. S. Abrams and W. Zhao (1995)
J. Biol. Chem. 270, 333-339
   Abstract »    Full Text »    PDF »
Cloning of a Grb2 isoform with apoptotic properties.
I Fath, F Schweighoffer, I Rey, M. Multon, J Boiziau, M Duchesne, and B Tocque (1994)
Science 264, 971-974
   Abstract »    PDF »
Aspects of growth factor signal transduction in the cell cytoplasm.
B. Panaretto (1994)
J. Cell Sci. 107, 747-752
   PDF »
Species specificity and organ, cellular and subcellular localization of the 100 kDa Ras GTPase activating protein.
P Mollat, A Fournier, C. Yang, E Alsat, Y Zhang, D Evain-Brion, J Grassi, and M. Thang (1994)
J. Cell Sci. 107, 427-435
   Abstract »    PDF »
Expanded: a gene involved in the control of cell proliferation in imaginal discs.
M Boedigheimer and A Laughon (1993)
Development 118, 1291-1301
   Abstract »    PDF »
The Ras/p120 GTPase-activating Protein (GAP) Interaction Is Regulated by the p120 GAP Pleckstrin Homology Domain.
J. K. Drugan, K. Rogers-Graham, T. Gilmer, S. Campbell, and G. J. Clark (2000)
J. Biol. Chem. 275, 35021-35027
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)