University of Virginia, Department of Molecular Physiology and Biological Physics, Charlottesville, VA 22908, USA.
Trends Cardiovasc Med. 2012 Jul;22(5):122-7. doi: 10.1016/j.tcm.2012.07.007. Epub 2012 Aug 16.
In normal and diseased vascular smooth muscle (SM), the RhoA pathway, which is activated by multiple agonists through G protein-coupled receptors (GPCRs), plays a central role in regulating basal tone and peripheral resistance. Multiple RhoA GTP exchange factors (GEFs) are expressed in SM, raising the possibility that specific agonists coupled to specific GPCRs may couple to distinct RhoGEFs and provide novel therapeutic targets. This review focuses on the function and mechanisms of activation of p63RhoGEF (Arhgef 25; GEFT) recently identified in SM and its possible role in selective targeting of RhoA-mediated regulation of basal blood pressure through agonists that couple through G(αq/11).
在正常和病变的血管平滑肌(SM)中,RhoA 通路通过 G 蛋白偶联受体(GPCRs)被多种激动剂激活,在调节基础张力和外周阻力方面发挥着核心作用。SM 中表达多种 RhoA GTP 交换因子(GEFs),这使得特定的激动剂与特定的 GPCR 偶联可能与不同的 RhoGEFs 偶联,并提供新的治疗靶点。本综述重点介绍了最近在 SM 中鉴定的 p63RhoGEF(Arhgef25;GEFT)的功能和激活机制,以及它在通过与 G(αq/11)偶联的激动剂选择性靶向 RhoA 介导的基础血压调节中的可能作用。