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首页> 外文期刊>Molecular and Cellular Biology >Human CNK1 Acts as a Scaffold Protein, Linking Rho and Ras Signal Transduction Pathways
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Human CNK1 Acts as a Scaffold Protein, Linking Rho and Ras Signal Transduction Pathways

机译：人类CNK1充当支架蛋白，连接Rho和Ras信号转导途径

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Rho family GTPases act as molecular switches to control a variety of cellular responses, including cytoskeletal rearrangements, changes in gene expression, and cell transformation. In the active, GTP-bound state, Rho interacts with an ever-growing number of effector molecules, which promote distinct biochemical pathways. Here, we describe the isolation of hCNK1, the human homologue of Drosophila connector enhancer of ksr, as an effector for Rho. hCNK1 contains several protein-protein interaction domains, and Rho interacts with one of these, the PH domain, in a GTP-dependent manner. A mutant hCNK1, which is unable to bind to Rho, or depletion of endogenous hCNK1 by using RNA interference inhibits Rho-induced gene expression via serum response factor but has no apparent effect on Rho-induced stress fiber formation, suggesting that it acts as a specific effector for transcriptional, but not cytoskeletal, activation pathways. Finally, hCNK1 associates with Rhophilin and RalGDS, Rho and Ras effector molecules, respectively, suggesting that it acts as a scaffold protein to mediate cross talk between the two pathways.
机译：Rho家族的GTPases充当分子开关，控制各种细胞应答，包括细胞骨架重排，基因表达变化和细胞转化。在活跃的，与GTP结合的状态下，Rho与数量不断增长的效应分子相互作用，从而促进独特的生化途径。在这里，我们描述了hCNK1的分离，hCNK1是果蝇Rem的效应子，是果蝇c增强子的人类同源物。 hCNK1包含几个蛋白质-蛋白质相互作用域，Rho以依赖GTP的方式与其中一个PH域相互作用。不能与Rho结合的突变hCNK1或通过使用RNA干扰而耗尽内源性hCNK1的突变体，可通过血清反应因子抑制Rho诱导的基因表达，但对Rho诱导的应激纤维形成没有明显影响，表明它起着转录但不是细胞骨架激活途径的特异性效应子。最后，hCNK1分别与Rhophilin和RalGDS，Rho​​和Ras效应子分子缔合，表明它充当支架蛋白来介导两条途径之间的串扰。

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