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 April 1988:
Vol. 240. no. 4851, pp. 518 - 521
DOI: 10.1126/science.2833817
Prev | Table of Contents | Next

Articles

Science, Vol 240, Issue 4851, 518-521
Copyright © 1988 by American Association for the Advancement of Science

articles

Guanosine triphosphatase activating protein (GAP) interacts with the p21 ras effector binding domain

H Adari, DR Lowy, BM Willumsen, CJ Der, and F McCormick

Department of Molecular Biology, Cetus Corporation, Emeryville, CA 94608.

A cytoplasmic protein that greatly enhances the guanosine triphosphatase (GTPase) activity of N-ras protein but does not affect the activity of oncogenic ras mutants has been recently described. This protein (GAP) is shown here to be ubiquitous in higher eukaryotes and to interact with H-ras as well as with N-ras proteins. To identify the region of ras p21 with which GAP interacts, 21 H-ras mutant proteins were purified and tested for their ability to undergo stimulation of GTPase activity by GAP. Mutations in nonessential regions of H-ras p21 as well as mutations in its carboxyl-terminal domain (residues 165-185) and purine binding region (residues 117 and 119) did not decrease the ability of the protein to respond to GAP. In addition, an antibody against the carboxyl-terminal domain did not block GAP activity, supporting the conclusion that GAP does not interact with this region. Transforming mutations at positions 12, 59, and 61 (the phosphoryl binding region) abolished GTPase stimulation by GAP. Point mutations in the putative effector region of ras p21 (amino acids 35, 36, and 38) were also insensitive to GAP. However, a point mutation at position 39, shown previously not to impair effector function, did not alter GAP-p21 interaction. These results indicate that GAP interaction may be essential for ras p21 biological activity and that it may be a ras effector protein.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Statins synergistically potentiate 7-hydroxystaurosporine (UCN-01) lethality in human leukemia and myeloma cells by disrupting Ras farnesylation and activation.
Y. Dai, P. Khanna, S. Chen, X.-Y. Pei, P. Dent, and S. Grant (2007)
Blood 109, 4415-4423
   Abstract »    Full Text »    PDF »
An Alliance between Ras GTPase-activating Protein, Filamin C, and Ras GTPase-activating Protein SH3 Domain-binding Protein Regulates Myocyte Growth.
J. Lypowy, I.-Y. Chen, and M. Abdellatif (2005)
J. Biol. Chem. 280, 25717-25728
   Abstract »    Full Text »    PDF »
Pituitary Adenylyl Cyclase-activating Polypeptide 38 Reduces Astroglial Proliferation by Inhibiting the GTPase RhoA.
D. K. Meyer, C. Fischer, U. Becker, I. Gottsching, S. Boutillier, C. Baermann, G. Schmidt, N. Klugbauer, and J. Leemhuis (2005)
J. Biol. Chem. 280, 25258-25266
   Abstract »    Full Text »    PDF »
Ras GTPase-activating Protein Binds to Akt and Is Required for Its Activation.
Y. Yue, J. Lypowy, N. Hedhli, and M. Abdellatif (2004)
J. Biol. Chem. 279, 12883-12889
   Abstract »    Full Text »    PDF »
The Novel Rho GTPase-activating Protein Family Protein, Rga8, Provides a Potential Link between Cdc42/p21-activated Kinase and Rho Signaling Pathways in the Fission Yeast, Schizosaccharomyces pombe.
P. Yang, Y. Qyang, G. Bartholomeusz, X. Zhou, and S. Marcus (2003)
J. Biol. Chem. 278, 48821-48830
   Abstract »    Full Text »    PDF »
Dnm1p Gtpase-Mediated Mitochondrial Fission Is a Multi-Step Process Requiring the Novel Integral Membrane Component Fis1p.
A.D. Mozdy, J.M. McCaffery, and J.M. Shaw (2000)
J. Cell Biol. 151, 367-380
   Abstract »    Full Text »    PDF »
Functions and Functional Domains of the GTPase Cdc42p.
K. G. Kozminski, A. J. Chen, A. A. Rodal, and D. G. Drubin (2000)
Mol. Biol. Cell 11, 339-354
   Abstract »    Full Text »
Activated MEK Stimulates Expression of AP-1 Components Independently of Phosphatidylinositol 3-Kinase (PI3-Kinase) but Requires a PI3-Kinase Signal To Stimulate DNA Synthesis.
I. Treinies, H. F. Paterson, S. Hooper, R. Wilson, and C. J. Marshall (1999)
Mol. Cell. Biol. 19, 321-329
   Abstract »    Full Text »    PDF »
Association of Rab25 and Rab11a with the Apical Recycling System of Polarized Madin-Darby Canine Kidney Cells.
J. E. Casanova, X. Wang, R. Kumar, S. G. Bhartur, J. Navarre, J. E. Woodrum, Y. Altschuler, G. S. Ray, and J. R. Goldenring (1999)
Mol. Biol. Cell 10, 47-61
   Abstract »    Full Text »
The Dynamin-related GTPase, Dnm1p, Controls Mitochondrial Morphology in Yeast.
D. Otsuga, B. R. Keegan, E. Brisch, J. W. Thatcher, G. J. Hermann, W. Bleazard, and J. M. Shaw (1998)
J. Cell Biol. 143, 333-349
   Abstract »    Full Text »    PDF »
Mitochondrial Fusion in Yeast Requires the Transmembrane GTPase Fzo1p.
G. J. Hermann, J. W. Thatcher, J. P. Mills, K. G. Hales, M. T. Fuller, J. Nunnari, and J. M. Shaw (1998)
J. Cell Biol. 143, 359-373
   Abstract »    Full Text »    PDF »
Different Regions of Rho Determine Rho-selective Binding of Different Classes of Rho Target Molecules.
K. Fujisawa, P. Madaule, T. Ishizaki, G. Watanabe, H. Bito, Y. Saito, A. Hall, and S. Narumiya (1998)
J. Biol. Chem. 273, 18943-18949
   Abstract »    Full Text »    PDF »
Functional Consequences of Monoglucosylation of Ha-Ras at Effector Domain Amino Acid Threonine 35.
C. Herrmann, M. R. Ahmadian, F. Hofmann, and I. Just (1998)
J. Biol. Chem. 273, 16134-16139
   Abstract »    Full Text »    PDF »
Catalytic Domain of the p120 Ras GAP Binds to Rab5 and Stimulates Its GTPase Activity.
K. Liu and G. Li (1998)
J. Biol. Chem. 273, 10087-10090
   Abstract »    Full Text »    PDF »
Equilibrium and Kinetic Study of the Conformational Transition toward the Active State of p21Ha-ras, Induced by the Binding of BeF3- to the GDP-bound State, in the Absence of GTPase-activating Proteins.
J. F. Diaz, A. Sillen, and Y. Engelborghs (1997)
J. Biol. Chem. 272, 23138-23143
   Abstract »    Full Text »    PDF »
Enhancement of Protein Kinase C-dependent O[IMAGE](2) Production in Epstein-Barr Virus-transformed B Lymphocytes by p120[IMAGE] Antisense Oligonucleotide.
E. Schmid, J. A. Koziol, and B. M. Babior (1996)
J. Biol. Chem. 271, 9320-9325
   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 »
A Conserved Region of c-Ha-Ras Is Required for Efficient GTPase Stimulation by GTPase Activating Protein but Not Neurofibromin.
J. Yoder-Hill, M. Golubic, and D. W. Stacey (1995)
J. Biol. Chem. 270, 27615-27621
   Abstract »    Full Text »    PDF »
Cyclic AMP-dependent Activation of Rap1b.
D. L. Altschuler, S. N. Peterson, M. C. Ostrowski, and E. G. Lapetina (1995)
J. Biol. Chem. 270, 10373-10376
   Abstract »    Full Text »    PDF »
A Constitutive Effector Region on the C-terminal Side of Switch I of the Ras Protein.
J. Fujita-Yoshigaki, M. Shirouzu, Y. Ito, S. Hattori, S. Furuyama, S. Nishimura, and S. Yokoyama (1995)
J. Biol. Chem. 270, 4661-4667
   Abstract »    Full Text »    PDF »
Quantitative Analysis of the Complex between p21[IMAGE] and the Ras-binding Domain of the Human Raf-1 Protein Kinase.
C. Herrmann, G. A. Martin, and A. Wittinghofer (1995)
J. Biol. Chem. 270, 2901-2905
   Abstract »    Full Text »    PDF »
Tyrosine kinase-stimulated guanine nucleotide exchange activity of Vav in T cell activation.
E Gulbins, K. Coggeshall, G Baier, S Katzav, P Burn, and A Altman (1993)
Science 260, 822-825
   Abstract »    PDF »
Heterogeneous amino acids in Ras and Rap1A specifying sensitivity to GAP proteins.
K Zhang, A. Papageorge, P Martin, W. Vass, Z Olah, P. Polakis, F McCormick, and D. Lowy (1991)
Science 254, 1630-1634
   Abstract »    PDF »
SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins.
C. Koch, D Anderson, M. Moran, C Ellis, and T Pawson (1991)
Science 252, 668-674
   Abstract »    PDF »
Regulation of ras p21 by GTPase Activating Proteins.
F. McCormick, G.A. Martin, R. Clark, G. Bollag, and P. Polakis (1991)
Cold Spring Harb Symp Quant Biol 56, 237-241
   Abstract »    PDF »
A cytoplasmic protein inhibits the GTPase activity of H-Ras in a phospholipid-dependent manner.
M. Tsai, C. Yu, and D. Stacey (1990)
Science 250, 982-985
   Abstract »    PDF »
The cellular functions of small GTP-binding proteins.
A Hall (1990)
Science 249, 635-640
   Abstract »    PDF »
Inhibition of GTPase activating protein stimulation of Ras-p21 GTPase by the Krev-1 gene product.
M Frech, J John, V Pizon, P Chardin, A Tavitian, R Clark, F McCormick, and A Wittinghofer (1990)
Science 249, 169-171
   Abstract »    PDF »
A cytosolic protein catalyzes the release of GDP from p21ras.
A Wolfman and I. Macara (1990)
Science 248, 67-69
   Abstract »    PDF »
Binding of GAP to activated PDGF receptors.
A Kazlauskas, C Ellis, T Pawson, and J. Cooper (1990)
Science 247, 1578-1581
   Abstract »    PDF »
Molecular switch for signal transduction: structural differences between active and inactive forms of protooncogenic ras proteins.
M. Milburn, L Tong, A. deVos, A Brunger, Z Yamaizumi, S Nishimura, and S. Kim (1990)
Science 247, 939-945
   Abstract »    PDF »
Activation of the cellular proto-oncogene product p21Ras by addition of a myristylation signal.
J. Buss, P. Solski, J. Schaeffer, M. MacDonald, and C. Der (1989)
Science 243, 1600-1603
   Abstract »    PDF »
The effect of GTPase activating protein upon ras is inhibited by mitogenically responsive lipids.
M. Tsai, C. Yu, F. Wei, and D. Stacey (1989)
Science 243, 522-526
   Abstract »    PDF »
Molecular cloning of two types of GAP complementary DNA from human placenta.
M Trahey, G Wong, R Halenbeck, B Rubinfeld, G. Martin, M Ladner, C. Long, W. Crosier, K Watt, K Koths, et al. (1988)
Science 242, 1697-1700
   Abstract »    PDF »
ras Oncogene Proteins: Three-dimensional Structures, Functional Implications, and a Model for Signal Transducer.
S.-H. Kim, A.M. de Vos, L. Tong, M.V. Milburn, P.M. Matias, J. Jancarik, E. Ohtsuka, and S. Nishimura (1988)
Cold Spring Harb Symp Quant Biol 53, 273-281
   Abstract »    PDF »
Studies of RAS Function in the Yeast Saccharomyces cerevisiae.
M. Wigler, J. Field, S. Powers, D. Broek, T. Toda, S. Cameron, J. Nikawa, T. Michaeli, J. Colicelli, and K. Ferguson (1988)
Cold Spring Harb Symp Quant Biol 53, 649-655
   Abstract »    PDF »
Interaction of ras p21 Proteins with GTPase Activating Protein.
F. McCormick, H. Adari, M. Trahey, R. Halenbeck, K. Koths, G.A. Martin, W.J. Crosier, K. Watt, B. Rubinfeld, and G. Wong (1988)
Cold Spring Harb Symp Quant Biol 53, 849-854
   Abstract »    PDF »
Analysis of Mammalian ras Effector Function.
A. Hall, C. Cales, J.F. Hancock, A. Lloyd, A. Self, S. Gardener, M.D. Houslay, M.J.O. Wakelam, and C.J. Marshall (1988)
Cold Spring Harb Symp Quant Biol 53, 855-862
   Abstract »    PDF »
Critical Role of Cellular ras Proteins in Proliferative Signal Transduction.
D.W. Stacey, M.-H. Tsai, C.-L. Yu, and J.K. Smith (1988)
Cold Spring Harb Symp Quant Biol 53, 871-881
   Abstract »    PDF »
Point Mutants of c-Raf-1 RBD with Elevated Binding to v-Ha-Ras.
M. Fridman, H. Maruta, J. Gonez, F. Walker, H. Treutlein, J. Zeng, and A. Burgess (2000)
J. Biol. Chem. 275, 30363-30371
   Abstract »    Full Text »    PDF »
Activation of Cell Division Protein FtsZ. CONTROL OF SWITCH LOOP T3 CONFORMATION BY THE NUCLEOTIDE gamma -PHOSPHATE.
J. F. Diaz, A. Kralicek, J. Mingorance, J. M. Palacios, M. Vicente, and J. M. Andreu (2001)
J. Biol. Chem. 276, 17307-17315
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

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