Zohn I M, Campbell S L, Khosravi-Far R, Rossman K L, Der C J
Department of Pharmacology, MIT, Cambridge, Massachusetts 02139, USA.
Oncogene. 1998 Sep 17;17(11 Reviews):1415-38. doi: 10.1038/sj.onc.1202181.
The Rho family of small GTPases has attracted considerable research interest over the past 5 years. During this time, we have witnessed a remarkable increase in our knowledge of the biochemistry and biology of these Ras-related proteins. Thus, Rho family proteins have begun to rival, if not overshadow, interest in their more celebrated cousins, the Ras oncogene proteins. The fascination in Rho family proteins is fueled primarily by two major observations. First, like Ras, Rho family proteins serve as guanine nucleotide-regulated binary switches that control signaling pathways that in turn regulate diverse cellular processes. Rho family proteins are key components in cellular processes that control the organization of the actin cytoskeleton, activate kinase cascades, regulate gene expression, regulate membrane trafficking, promote growth transformation and induce apoptosis. Second, at least five Rho family proteins have been implicated as critical regulators of oncogenic Ras transformation. Thus, it is suspected that Rho family proteins contribute significantly to the aberrant growth properties of Ras-transformed cells. Rho family proteins are also critical mediators of the transforming actions of other transforming proteins and include Dbl family oncogene proteins, G protein-coupled receptors and G protein alpha subunits. Thus, Rho family proteins may be key components for the transforming actions of diverse oncogene proteins. Major aims of Rho family protein studies are to define the molecular mechanism by which Rho family proteins regulate such a diverse spectrum of cellular behavior. These efforts may reveal novel targets for the development of anti-Ras and anti-cancer drugs.
在过去5年里，小GTP酶的Rho家族吸引了相当多的研究兴趣。在此期间，我们见证了对这些与Ras相关蛋白质的生物化学和生物学知识的显著增长。因此，Rho家族蛋白质即便没有盖过，也已开始与其更为著名的同类——Ras癌基因蛋白质相匹敌，引发人们的兴趣。对Rho家族蛋白质的痴迷主要源于两大发现。其一，与Ras一样，Rho家族蛋白质充当鸟嘌呤核苷酸调节的二元开关，控制着进而调节各种细胞过程的信号通路。Rho家族蛋白质是控制肌动蛋白细胞骨架组织、激活激酶级联反应、调节基因表达、调节膜运输、促进生长转化和诱导细胞凋亡的细胞过程中的关键成分。其二，至少有五种Rho家族蛋白质被认为是致癌Ras转化的关键调节因子。因此，有人怀疑Rho家族蛋白质对Ras转化细胞的异常生长特性有重大贡献。Rho家族蛋白质也是其他转化蛋白转化作用的关键介质，包括Dbl家族癌基因蛋白质、G蛋白偶联受体和G蛋白α亚基。因此，Rho家族蛋白质可能是多种癌基因蛋白质转化作用的关键成分。对Rho家族蛋白质研究的主要目标是确定Rho家族蛋白质调节如此多样的细胞行为的分子机制。这些努力可能会揭示抗Ras和抗癌药物开发的新靶点。
