Park Frank
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee
J Pharmacol Exp Ther. 2015 May;353(2):235-45. doi: 10.1124/jpet.115.222695. Epub 2015 Jan 27.
Heterotrimeric G proteins play a crucial role in regulating signal processing to maintain normal cellular homeostasis, and subtle perturbations in its activity can potentially lead to the pathogenesis of renal disorders or diseases. Cell-surface receptors and accessory proteins, which normally modify and organize the coupling of individual G protein subunits, contribute to the regulation of heterotrimeric G protein activity and their convergence and/or divergence of downstream signaling initiated by effector systems. Activators of G protein signaling (AGS) are a family of accessory proteins that intervene at multiple distinct points during the activation-inactivation cycle of G proteins, even in the absence of receptor stimulation. Perturbations in the expression of individual AGS proteins have been reported to modulate signal transduction pathways in a wide array of diseases and disorders within the brain, heart, immune system, and more recently, the kidney. This review will provide an overview of the expression profile, localization, and putative biologic role of the AGS family in the context of normal and diseased states of the kidney.
异源三聚体G蛋白在调节信号转导以维持正常细胞稳态中起关键作用，其活性的细微扰动可能潜在地导致肾脏疾病的发病机制。细胞表面受体和辅助蛋白通常修饰和组织单个G蛋白亚基的偶联，有助于调节异源三聚体G蛋白的活性及其由效应系统引发的下游信号的汇聚和/或发散。G蛋白信号激活剂（AGS）是一类辅助蛋白，即使在没有受体刺激的情况下，也能在G蛋白的激活-失活循环中的多个不同点进行干预。据报道，单个AGS蛋白表达的扰动可调节大脑、心脏、免疫系统以及最近发现的肾脏等多种疾病和病症中的信号转导途径。本综述将概述AGS家族在肾脏正常和疾病状态下的表达谱、定位及假定的生物学作用。
