Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, USA; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Cell Signal. 2020 Nov;75:109765. doi: 10.1016/j.cellsig.2020.109765. Epub 2020 Aug 31.
Regulator of G protein signaling 10 (RGS10) belongs to the superfamily of RGS proteins, defined by the presence of a conserved RGS domain that canonically binds and deactivates heterotrimeric G-proteins. RGS proteins act as GTPase activating proteins (GAPs), which accelerate GTP hydrolysis on the G-protein α subunits and result in termination of signaling pathways downstream of G protein-coupled receptors. RGS10 is the smallest protein of the D/R12 subfamily and selectively interacts with Gαi proteins. It is widely expressed in many cells and tissues, with the highest expression found in the brain and immune cells. RGS10 expression is transcriptionally regulated via epigenetic mechanisms. Although RGS10 lacks multiple of the defined regulatory domains found in other RGS proteins, RGS10 contains post-translational modification sites regulating its expression, localization, and function. Additionally, RGS10 is a critical protein in the regulation of physiological processes in multiple cells, where dysregulation of its expression has been implicated in various diseases including Parkinson's disease, multiple sclerosis, osteopetrosis, chemoresistant ovarian cancer and cardiac hypertrophy. This review summarizes RGS10 features and its regulatory mechanisms, and discusses the known functions of RGS10 in cellular physiology and pathogenesis of several diseases.
G 蛋白信号调节因子 10（RGS10）属于 RGS 蛋白超家族，其特征是存在保守的 RGS 结构域，该结构域能够特异性结合并失活异三聚体 G 蛋白。RGS 蛋白作为 G 蛋白激活蛋白（GAP），可加速 G 蛋白α亚基上的 GTP 水解，从而终止 G 蛋白偶联受体下游的信号通路。RGS10 是 D/R12 亚家族中最小的蛋白，可选择性地与 Gαi 蛋白相互作用。它在许多细胞和组织中广泛表达，在大脑和免疫细胞中表达水平最高。RGS10 的表达受转录调控，其通过表观遗传机制进行调控。虽然 RGS10 缺乏其他 RGS 蛋白中存在的多个定义的调节结构域，但 RGS10 包含调节其表达、定位和功能的翻译后修饰位点。此外，RGS10 是多种细胞中生理过程调节的关键蛋白，其表达失调与帕金森病、多发性硬化症、骨质石化症、化疗耐药性卵巢癌和心肌肥厚等多种疾病有关。本综述总结了 RGS10 的特征及其调控机制，并讨论了 RGS10 在几种疾病的细胞生理学和发病机制中的已知功能。
