Inhibition of GTPase activating protein stimulation of Ras-p21 GTPase by the Krev-1 gene product |
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| Authors: | M Frech J John V Pizon P Chardin A Tavitian R Clark F McCormick A Wittinghofer |
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| Affiliation: | Max-Planck-Institute für medizinische Forschung, Abteilung Biophysik, Heidelberg, Germany. |
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| Abstract: | 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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