Sinha Soniya, Yang Wannian
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, United States.
Cell Signal. 2008 Nov;20(11):1927-34. doi: 10.1016/j.cellsig.2008.05.002. Epub 2008 May 16.
The Rho family GTPase Cdc42 regulates cytoskeletal organization and membrane trafficking in physiological processes such as cell proliferation, motility and polarity. Aberrant activation of Cdc42 results in pathogenesis, such as tumorigenesis and tumor progression, cardiovascular diseases, diabetes, and neuronal degenerative diseases. The activation of Cdc42 in response to upstream signals is mediated by guanine nucleotide exchange factors (GEFs), which converse GDP-bound inactive form to the GTP-bound active form of Cdc42. The activated Cdc42 transduces signals to downstream effectors and generates cellular effects. This review will discuss the molecular mechanism of activation of Cdc42 and postulate that signaling specificity of Cdc42 is conferred by the GEF/GTPase/Effector (GGE) complexes in response to external stimuli.
Rho家族GTP酶Cdc42在细胞增殖、运动和极性等生理过程中调节细胞骨架组织和膜运输。Cdc42的异常激活会导致发病机制，如肿瘤发生和肿瘤进展、心血管疾病、糖尿病和神经退行性疾病。Cdc42对上游信号的响应激活是由鸟嘌呤核苷酸交换因子（GEF）介导的，GEF将结合GDP的无活性形式转化为结合GTP的Cdc42活性形式。激活的Cdc42将信号转导至下游效应器并产生细胞效应。本综述将讨论Cdc42激活的分子机制，并推测Cdc42的信号特异性是由GEF/GTP酶/效应器（GGE）复合物在响应外部刺激时赋予的。
