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首页> 外文期刊>Molecular and Cellular Biology >p190 RhoGAP, the major RasGAP-associated protein, binds GTP directly.
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p190 RhoGAP, the major RasGAP-associated protein, binds GTP directly.

机译:p190 RhoGAP是与RasGAP相关的主要蛋白,直接与GTP结合。

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In mitogenically stimulated cells, a specific complex forms between the Ras GTPase-activating protein (RasGAP) and the cellular protein p190. We have previously reported that p190 contains a carboxy-terminal domain that functions as a GAP for the Rho family GTPases. Thus, the RasGAP-p190 complex may serve to couple Ras- and Rho-mediated signalling pathways. In addition to its RhoGAP domain, p190 contains an amino-terminal domain that contains sequence motifs found in all known GTPases. Here, we report that p190 binds GTP and GDP through this conserved domain and that the structural requirements for binding are similar to those seen with other GTPases. While the purified protein is unable to hydrolyze GTP, we detect an activity in cell lysates that can promote GTP hydrolysis by p190. A mutated form of p190 that fails to bind nucleotide retains its RasGAP binding and RhoGAP activities, indicating that GTP binding by p190 is not required for these functions. The sequence of p190 in the GTP-binding domain, which shares structural features with both the Ras-like small GTPases and the larger G proteins, suggests that this protein defines a novel class of guanine nucleotide-binding proteins.
机译:在促有丝分裂的细胞中,Ras GTPase激活蛋白(RasGAP)和细胞蛋白p190之间形成特定的复合物。先前我们已经报道过p190含有一个羧基末端结构域,该结构域充当Rho家族GTPases的GAP。因此,RasGAP-p190复合物可用于偶联Ras和Rho介导的信号通路。除其RhoGAP结构域外,p190还包含一个氨基末端结构域,该结构域包含在所有已知GTPases中均发现的序列基序。在这里,我们报告说p190通过这个保守域结合GTP和GDP,并且结合的结构要求与其他GTPases相似。虽然纯化的蛋白质无法水解GTP,但我们检测到细胞裂解物中的活性可以促进p190水解GTP。无法结合核苷酸的p190突变形式保留其RasGAP结合和RhoGAP活性,表明这些功能不需要p190的GTP结合。 GTP结合域中的p190序列与Ras样小GTP酶和较大的G蛋白具有相同的结构特征,这表明该蛋白定义了一类新型的鸟嘌呤核苷酸结合蛋白。

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