Inhibition of GTPase activating protein stimulation of Ras-p21 GTPase by the Krev-1 gene product

被引:247
作者
Frech, M
John, J
Pizon, V
Chardin, P
Tavitian, A
Clark, R
Mccormick, F
Wittinghofer, A [1 ]
机构
[1] Max Planck Inst Med Forsch, Abt Biophys, Jahnstr 29, D-6900 Heidelberg, GERMANY
[2] INSERM, U248, Fac Med Lariboisiere St Louis, F-75010 Paris, FRANCE
[3] Cetus Corp, Dept Mol Biol, Emeryville, CA 94608 USA
关键词
D O I
10.1126/science.2164710
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 Rasp21 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.
引用
收藏
页码:169 / 171
页数:3
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