Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
Nat Rev Mol Cell Biol. 2016 Aug;17(8):496-510. doi: 10.1038/nrm.2016.67. Epub 2016 Jun 15.
Rho GTPases regulate cytoskeletal and cell adhesion dynamics and thereby coordinate a wide range of cellular processes, including cell migration, cell polarity and cell cycle progression. Most Rho GTPases cycle between a GTP-bound active conformation and a GDP-bound inactive conformation to regulate their ability to activate effector proteins and to elicit cellular responses. However, it has become apparent that Rho GTPases are regulated by post-translational modifications and the formation of specific protein complexes, in addition to GTP-GDP cycling. The canonical regulators of Rho GTPases - guanine nucleotide exchange factors, GTPase-activating proteins and guanine nucleotide dissociation inhibitors - are regulated similarly, creating a complex network of interactions to determine the precise spatiotemporal activation of Rho GTPases.
Rho GTPases 调节细胞骨架和细胞黏附动力学,从而协调广泛的细胞过程,包括细胞迁移、细胞极性和细胞周期进程。大多数 Rho GTPases 在 GTP 结合的活性构象和 GDP 结合的非活性构象之间循环,以调节它们激活效应蛋白和引发细胞反应的能力。然而,现在已经很明显,Rho GTPases 除了 GTP-GDP 循环外,还受到翻译后修饰和特定蛋白质复合物形成的调节。Rho GTPases 的经典调节因子 - 鸟嘌呤核苷酸交换因子、GTPase 激活蛋白和鸟嘌呤核苷酸解离抑制剂 - 受到类似的调节,形成一个复杂的相互作用网络,以确定 Rho GTPases 的精确时空激活。