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Science 13 July 1990:
Vol. 249. no. 4965, pp. 169 - 171
DOI: 10.1126/science.2164710
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Articles

Science, Vol 249, Issue 4965, 169-171
Copyright © 1990 by American Association for the Advancement of Science

articles

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

Max-Planck-Institute fur medizinische Forschung, Abteilung Biophysik, Heidelberg, Germany.

Krev-1 is known to suppress transformation by ras. However, the mechanism of the suppression is unclear. The protein product of Krev-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 Krev-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.


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