Inhibition of GTPase activating protein stimulation of Ras-p21 GTPase by the Krev-1 gene product
Inhibition of GTPase activating protein stimulation of Ras-p21 GTPase by the Krev-1 gene product
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DOI：
10.1126/science.2164710
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发表时间：
1990-07-13
期刊：
影响因子：
56.9
通讯作者：
Wittinghofer, A
中科院分区：
文献类型：
--
作者：
Frech, M;John, J;Wittinghofer, A
已知Krev-1抑制ras的转化。然而，抑制的机制尚不清楚。Krev-1的蛋白质产物Rap 1A-p21与Ras-p21蛋白在据信与鸟苷三磷酸酶（GTdR）活化蛋白（GAP）发生相互作用的区域相同。因此，测试了GAP与Rap 1A-p21相互作用的能力。Rap 1A-p21不被GAP激活，但与GAP紧密结合，并有效地竞争性抑制GAP介导的Ras-GT酶活性。GAP与Rap 1A-p21的结合是严格依赖于鸟苷三磷酸（GTP）的。Rap 1A-p21与GAP紧密结合的能力可能是Krev-1抑制ras转化的原因。这可能通过阻止GAP与Ras-p21或GAP介导的Ras GT3活性所必需的其他细胞蛋白质的相互作用而发生。
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 inhibition 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.