DOI: 10.1126/science.2164710. Inhibition of GTPase Activating Protein Stimulation of Ras-p21 GTPase by the K <i>rev</i> -1 Gene Product

Inhibition of GTPase Activating Protein Stimulation of Ras-p21 GTPase by the K rev -1 Gene Product

10.1126/science.2164710

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

K rev -1 is known to suppress transformation by ras . However, the mechanism of the suppression is unclear. The protein product of K rev -1, Rap1A-p21, is identical to Ras-p21 proteins in the region where interaction with guanosine triphosphatase (GTPase) activating protein (GAP) is believed to occur. Therefore, the ability of GAP to interact with Rap1A-p21 was tested. Rap1A-p21 was not activated by GAP but bound tightly to GAP and was an effective competitive inhibitor of GAP-mediated Ras-GTPase activity. Binding of GAP to Rap1A-p21 was strictly guanosine triphosphate (GTP)-dependent. The ability of Rap1A-p21 to bind tightly to GAP may account for K rev -1 suppression of transformation by ras . This may occur by preventing interaction of GAP with Ras-p21 or with other cellular proteins necessary for GAP-mediated Ras GTPase activity.

Bibliography

Frech, M., John, J., Pizon, V., Chardin, P., Tavitian, A., Clark, R., McCormick, F., & Wittinghofer, A. (1990). Inhibition of GTPase Activating Protein Stimulation of Ras-p21 GTPase by the K rev -1 Gene Product. Science, 249(4965), 169â171.

Authors 8

Matthias Frech (first)
Jacob John (additional)
Veronique Pizon (additional)
Pierre Chardin (additional)
Armand Tavitian (additional)
Robin Clark (additional)
Frank McCormick (additional)
Alfred Wittinghofer (additional)

References 24 Referenced 194

10.1126/science.2833817
10.1126/science.235.4787.458
CALES, C, THE CYTOPLASMIC PROTEIN GAP IS IMPLICATED AS THE TARGET FOR REGULATION BY THE RAS GENE-PRODUCT, NATURE 332: 548 (1988). (10.1038/332548a0) / NATURE (1988)
DEVER, T.E., GTP-BINDING DOMAIN - 3 CONSENSUS SEQUENCE ELEMENTS WITH DISTINCT SPACING, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 84: 1814 (1987). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1987)
10.1073/pnas.85.14.5026
GIBBS, J.B., XENOPUS OOCYTE GERMINAL-VESICLE BREAKDOWN INDUCED BY [VAL12]RAS IS INHIBITED BY A CYTOSOL-LOCALIZED RAS MUTANT, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 86: 6630 (1989). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1989)
10.1146/annurev.bi.56.070187.003151
HALLIDAY, K.R., J CYCLIC NUCLEOTIDE 9: 435 (1983). / J CYCLIC NUCLEOTIDE (1983)
JOHN, J, BIOCHEMICAL-PROPERTIES OF HA-RAS ENCODED P21-MUTANTS AND MECHANISM OF THE AUTOPHOSPHORYLATION REACTION, JOURNAL OF BIOLOGICAL CHEMISTRY 263: 11792 (1988). (10.1016/S0021-9258(18)37854-2) / JOURNAL OF BIOLOGICAL CHEMISTRY (1988)
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10.1126/science.2821624
10.1126/science.3201259
TUCKER, J, EXPRESSION OF P21 PROTEINS IN ESCHERICHIA-COLI AND STEREOCHEMISTRY OF THE NUCLEOTIDE-BINDING SITE, EMBO JOURNAL 5: 1351 (1986). (10.1002/j.1460-2075.1986.tb04366.x) / EMBO JOURNAL (1986)
UEDA, T, GTPASE ACTIVATING PROTEINS FOR THE SMG-21 GTP-BINDING PROTEIN HAVING THE SAME EFFECTOR DOMAIN AS THE RAS PROTEINS IN HUMAN-PLATELETS, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 159: 1411 (1989). (10.1016/0006-291X(89)92267-5) / BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (1989)
10.1038/335090a0

Dates

Type	When
Created	18 years, 11 months ago (Oct. 5, 2006, 6:10 p.m.)
Deposited	1 year, 7 months ago (Jan. 12, 2024, 5:22 a.m.)
Indexed	2 months, 1 week ago (June 27, 2025, 9:45 a.m.)
Issued	35 years, 1 month ago (July 13, 1990)
Published	35 years, 1 month ago (July 13, 1990)
Published Print	35 years, 1 month ago (July 13, 1990)

Funders 0

None

BibTeX

@article{Frech_1990, title={Inhibition of GTPase Activating Protein Stimulation of Ras-p21 GTPase by the K rev -1 Gene Product}, volume={249}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.2164710}, DOI={10.1126/science.2164710}, number={4965}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Frech, Matthias and John, Jacob and Pizon, Veronique and Chardin, Pierre and Tavitian, Armand and Clark, Robin and McCormick, Frank and Wittinghofer, Alfred}, year={1990}, month=jul, pages={169–171} }

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