小G蛋白RhoA与细胞发育

细胞发育是细胞内各种复杂反应在时间和空间上有序协调的过程, 包括细胞增殖、胞质分裂、细胞运动、细胞分化和组织生成等．作为G蛋白家族重要成员的RhoA起了重要的调控作用：在G蛋白调控因子(如GEF XPLN、 p115RhoGEF、p190RhoGAP等）的作用下,活化的RhoA依次与效应蛋白分子（如ROCK1/2、 mDia、 PRK1/2、 citron 激酶等）结合, 从而开启了下游的信号通路, 最终使细胞能够迅速地对外界刺激做出反应．干细胞是一类既能自我更新又能特异分化形成终末分化细胞的细胞, 而 RhoA对干细胞的自我更新和定向分化也起着“开关"作用, 对RhoA信号通路的调节调控了胚胎发生、神经发生、造血生成及成骨和肌肉生成等干细胞分化发育过程．肿瘤是正常细胞在各种因素长期作用下增殖异常的产物, 而RhoA异常表达与肿瘤的发生、侵润与转移密切相关, RhoA信号通路与p53等基因的交互作用在肿瘤的发育过程中也发挥了重要的作用．

Small GTPases RhoA and cell development

Cell development is a complex biochemical process with spatio-temporal regulations and activities harmoniously controlled in the cell．Small GTPases of the Ras superfamily are key regulators of diverse cellular and developmental events．RhoA is an important member of these small GTPases which is best known as one of the regulators of the actin cytoskeleton, but in addition it controls cell proliferation, cell movement, cell cytokinesis, cell differentiation and histogenesis and other biological responses．Controlled by many regulatory factors (e.g. GEF XPLN, p115RhoGEF, p190RhoGAP), RhoA has an intrinsic GTPase activity and shuttles between an inactive GDP-bound state and an active GTP-bound state, switches on and off to control the downstream signal transduction pathways and rapidly links the function of cell surface receptors to a variety of intracellular responses．The major effectors of RhoA include ROCK1/2, mDia, PRK1/2, Rhoteckin, Rhophillin, citron kinase, etc．In vertebrate embryonic development, RhoA not only maintains the basic cell movements, but also functions as a molecular switch for stem cell self-renewal and differentiation．RhoA is also required for the processes involving cell migration in development including embryogenesis, neurogenesis, hematopoiesis, osteogenesis and myogenesis．RhoA is essential for tumorigenesis, as it is overexpressed in several cancer cell lines, many of which are either highly metastatic or have defects in growth control．