Song Yan, An Zihao, Wang Jiepu, Xu Qiang, Li Jiayong, Tang Chao
National Clinical Research Center for Child Health of Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Pharmacol Res. 2025 Jul;217:107801. doi: 10.1016/j.phrs.2025.107801. Epub 2025 May 30.
Regulator of G protein signaling (RGS) proteins are critical modulators of G protein-coupled receptor (GPCR) signaling through their GTPase-activating protein (GAP) activity. RGS proteins are regulated at multiple levels, including the pre-transcription, transcription, and post-translation levels. Among the regulation patterns, post-translational modification (PTMs) can directly affect the regulation of G protein signaling by modulating the GAP activity of RGS proteins or indirectly regulate their function by affecting their subcellular localization and stability. The corresponding PTM behavior of a certain RGS protein is regulated by complex upstream factors and is closely related to multiple downstream signal transduction associated with G proteins. This complex regulatory relationship forms a dynamic and fine-tuned regulatory network within the cell. In this review, we methodically summarize the impact of diverse PTMs on RGS proteins and provide a comprehensive overview of their associated upstream regulatory factors and downstream signal pathway alterations. Furthermore, we explore the physiological and pathological states associated with PTM dysregulation. Additionally, we discuss the potential clinical application value of PTMs targeting RGS.
G蛋白信号调节蛋白（RGS）通过其GTP酶激活蛋白（GAP）活性，成为G蛋白偶联受体（GPCR）信号传导的关键调节因子。RGS蛋白在多个水平受到调控，包括转录前、转录和翻译后水平。在这些调控模式中，翻译后修饰（PTM）可通过调节RGS蛋白的GAP活性直接影响G蛋白信号传导的调控，或通过影响其亚细胞定位和稳定性间接调节其功能。特定RGS蛋白的相应PTM行为受复杂的上游因子调控，并与多个与G蛋白相关的下游信号转导密切相关。这种复杂的调控关系在细胞内形成了一个动态且精细调节的调控网络。在本综述中，我们系统地总结了不同PTM对RGS蛋白的影响，并全面概述了其相关的上游调控因子和下游信号通路变化。此外，我们探讨了与PTM失调相关的生理和病理状态。此外，我们还讨论了靶向RGS的PTM的潜在临床应用价值。
