Sasaki T, Takai Y
Department of Molecular Biology and Biochemistry, Osaka University Medical School, Suita, Japan.
Biochem Biophys Res Commun. 1998 Apr 28;245(3):641-5. doi: 10.1006/bbrc.1998.8253.
Recent extensive studies have clarified the functions of the small G protein superfamily, which consists of the Ras, Rho, Rab, Arf, Sar1, and Ran families (for reviews, Refs, 1 and 2). The Ras family regulates gene expression at least through the MAP kinase cascade; the Rho family mainly regulates reorganization of the actin cytoskeleton; the Rab, Arf, and Sar1 families regulate intracellular vesicle trafficking; and the Ran family regulates nuclear transport. Of these cellular functions, reorganization of the actin cytoskeleton, seen in the formation of filopodia, lamellipodia, and ruffles during cell motility, dynamically occurs at specific sites of cells. To regulate this type of dynamic cellular functions, temporal and spatial determination mechanisms of signal transduction would be important. Like other G proteins, small G proteins cycle between the GDP-bound inactive and GTP-bound active forms (1,2). They receive upstream signals through their regulators and transduce signals to downstream targets while they stay in the GTP-bound form. Thus, G proteins serve as timers. There are at least three types of regulators for small G proteins: GDP/GTP exchange protein (GEP) which stimulates conversion from the GDP-bound form to the GTP-bound form; GDP dissociation inhibitor (GDI) which inhibits this reaction; and GTPase activating protein (GAP) which stimulates conversion from the GTP-bound form to the GDP-bound form. Of these regulators, GDI has thus far been found for the Rho and Rab families. We have recently found that the Rho family-Rho GDI system plays an important role in spatial determination in the actin cytoskeletal control (3-6). We briefly describe here this function of the Rho family-Rho GDI system.
最近的广泛研究阐明了小G蛋白超家族的功能，该家族由Ras、Rho、Rab、Arf、Sar1和Ran家族组成（综述见参考文献1和2）。Ras家族至少通过丝裂原活化蛋白激酶级联反应调节基因表达；Rho家族主要调节肌动蛋白细胞骨架的重组；Rab、Arf和Sar1家族调节细胞内囊泡运输；而Ran家族调节核运输。在这些细胞功能中，肌动蛋白细胞骨架的重组，如在细胞运动过程中丝状伪足、片状伪足和褶皱的形成中所见，动态地发生在细胞的特定部位。为了调节这种类型的动态细胞功能，信号转导的时空确定机制将很重要。与其他G蛋白一样，小G蛋白在结合GDP的无活性形式和结合GTP的活性形式之间循环（1,2）。它们通过其调节因子接收上游信号，并在保持结合GTP的形式时将信号转导至下游靶点。因此，G蛋白起到定时器的作用。小G蛋白至少有三种类型的调节因子：刺激从结合GDP的形式向结合GTP的形式转化的GDP/GTP交换蛋白（GEP）；抑制此反应的GDP解离抑制剂（GDI）；以及刺激从结合GTP的形式向结合GDP的形式转化的GTP酶激活蛋白（GAP）。在这些调节因子中，迄今为止已在Rho和Rab家族中发现了GDI。我们最近发现，Rho家族-Rho GDI系统在肌动蛋白细胞骨架控制的空间确定中起重要作用（3-6）。我们在此简要描述Rho家族-Rho GDI系统的这一功能。
