Johnson D I
Department of Microbiology & Molecular Genetics and the Markey Center for Molecular Genetics, University of Vermont, Burlington, Vermont 05405,
Microbiol Mol Biol Rev. 1999 Mar;63(1):54-105. doi: 10.1128/MMBR.63.1.54-105.1999.
Cdc42p is an essential GTPase that belongs to the Rho/Rac subfamily of Ras-like GTPases. These proteins act as molecular switches by responding to exogenous and/or endogenous signals and relaying those signals to activate downstream components of a biological pathway. The 11 current members of the Cdc42p family display between 75 and 100% amino acid identity and are functional as well as structural homologs. Cdc42p transduces signals to the actin cytoskeleton to initiate and maintain polarized gorwth and to mitogen-activated protein morphogenesis. In the budding yeast Saccharomyces cerevisiae, Cdc42p plays an important role in multiple actin-dependent morphogenetic events such as bud emergence, mating-projection formation, and pseudohyphal growth. In mammalian cells, Cdc42p regulates a variety of actin-dependent events and induces the JNK/SAPK protein kinase cascade, which leads to the activation of transcription factors within the nucleus. Cdc42p mediates these processes through interactions with a myriad of downstream effectors, whose number and regulation we are just starting to understand. In addition, Cdc42p has been implicated in a number of human diseases through interactions with its regulators and downstream effectors. While much is known about Cdc42p structure and functional interactions, little is known about the mechanism(s) by which it transduces signals within the cell. Future research should focus on this question as well as on the detailed analysis of the interactions of Cdc42p with its regulators and downstream effectors.
Cdc42p是一种必需的GTP酶，属于Ras样GTP酶的Rho/Rac亚家族。这些蛋白质通过响应外源性和/或内源性信号并传递这些信号来激活生物途径的下游成分，从而起到分子开关的作用。Cdc42p家族的11个现有成员显示出75%至100%的氨基酸同一性，并且是功能和结构同源物。Cdc42p将信号转导至肌动蛋白细胞骨架，以启动和维持极化生长以及有丝分裂原激活蛋白形态发生。在芽殖酵母酿酒酵母中，Cdc42p在多种肌动蛋白依赖性形态发生事件中发挥重要作用，如芽出现、交配突起形成和假菌丝生长。在哺乳动物细胞中，Cdc42p调节多种肌动蛋白依赖性事件，并诱导JNK/SAPK蛋白激酶级联反应，从而导致细胞核内转录因子的激活。Cdc42p通过与大量下游效应器相互作用来介导这些过程，而我们才刚刚开始了解这些效应器的数量和调控。此外，Cdc42p通过与其调节因子和下游效应器相互作用，与多种人类疾病有关。虽然对Cdc42p的结构和功能相互作用了解很多，但对其在细胞内转导信号的机制知之甚少。未来的研究应聚焦于这个问题以及对Cdc42p与其调节因子和下游效应器相互作用的详细分析。
