Sternweis Paul C, Carter Angela M, Chen Zhe, Danesh Shahab M, Hsiung Ying-Fan, Singer William D
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Adv Protein Chem. 2007;74:189-228. doi: 10.1016/S0065-3233(07)74006-8.
Monomeric Rho GTPases regulate cellular dynamics through remodeling of the cytoskeleton, modulation of immediate signaling pathways, and longer-term regulation of gene transcription. One family of guanine nucleotide exchange factors for Rho proteins (RhoGEFs) provides a direct pathway for regulation of RhoA by cell surface receptors coupled to heterotrimeric G proteins. Some of these RhoGEFs also contain RGS domains that can attenuate signaling by the G(12) and G(13) proteins. The regulation provided by these RhoGEFs is defined by their selective regulation by specific G proteins, phosphorylation by kinases, and potential localization with signaling partners. Evidence of their physiological importance is derived from gene knockouts in Drosophila and mice. Current understanding of the basic regulatory mechanisms of these RhoGEFs is discussed. An overview of identified interactions with other signaling proteins suggests the growing spectrum of their involvement in numerous signaling pathways.
单体Rho GTP酶通过细胞骨架重塑、即时信号通路调节以及基因转录的长期调控来调节细胞动力学。Rho蛋白的鸟嘌呤核苷酸交换因子（RhoGEF）家族为与异源三聚体G蛋白偶联的细胞表面受体调节RhoA提供了一条直接途径。其中一些RhoGEF还含有RGS结构域，可减弱G(12)和G(13)蛋白的信号传导。这些RhoGEF提供的调节作用由它们受特定G蛋白的选择性调节、激酶的磷酸化作用以及与信号伴侣的潜在定位所决定。它们生理重要性的证据来自果蝇和小鼠的基因敲除实验。本文讨论了目前对这些RhoGEF基本调节机制的理解。已确定的与其他信号蛋白相互作用的概述表明它们参与众多信号通路的范围在不断扩大。
