Suzuki Nobuchika, Hajicek Nicole, Kozasa Tohru
Laboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
Neurosignals. 2009;17(1):55-70. doi: 10.1159/000186690. Epub 2009 Feb 12.
Accumulating data indicate that G12 subfamily (Galpha12/13)-mediated signaling pathways play pivotal roles in a variety of physiological processes, while aberrant regulation of this pathway has been identified in various human diseases. It has been demonstrated that Galpha12/13-mediated signals form networks with other signaling proteins at various levels, from cell surface receptors to transcription factors, to regulate cellular responses. Galpha12/13 have slow rates of nucleotide exchange and GTP hydrolysis, and specifically target RhoGEFs containing an amino-terminal RGS homology domain (RH-RhoGEFs), which uniquely function both as a GAP and an effector for Galpha12/13. In this review, we will focus on the mechanisms regulating the Galpha12/13 signaling system, particularly the Galpha12/13-RH-RhoGEF-Rho pathway, which can regulate a wide variety of cellular functions from migration to transformation.
越来越多的数据表明，G12亚家族（Gα12/13）介导的信号通路在多种生理过程中起关键作用，而该通路的异常调节已在多种人类疾病中被发现。已经证明，Gα12/13介导的信号在从细胞表面受体到转录因子的各个水平上与其他信号蛋白形成网络，以调节细胞反应。Gα12/13的核苷酸交换和GTP水解速率较慢，并特异性靶向含有氨基末端RGS同源结构域的RhoGEF（RH-RhoGEF），后者独特地兼具Gα12/13的GAP和效应器功能。在本综述中，我们将重点关注调节Gα12/13信号系统的机制，特别是Gα12/13-RH-RhoGEF-Rho通路，该通路可调节从迁移到转化的多种细胞功能。
