Regulators of G protein signaling (RGS) and RGS-like proteins are a family (>30 members) of highly diverse, multifunctional signaling proteins that bind directly to activated G alpha subunits. Family members are defined by a shared RGS domain, which is responsible for G alpha binding and markedly stimulates the GTPase activity of G alpha subunits leading to their deactivation and termination of downstream signals. Although much has been learned in recent years about the biochemistry of RGS/G alpha interactions, considerably less is known about the broader cellular roles and regulation of RGS proteins. Recent findings indicate that cellular mechanisms such as covalent modification, alternative gene splicing, and protein processing can dictate the activity and subcellular localization of RGS proteins. Many family members also directly link G proteins to a growing list of signaling proteins with diverse cellular roles. New findings indicate that RGS proteins act not as dedicated inhibitors but, rather, as tightly regulated modulators and integrators of G protein signaling. In some cases, RGS proteins modulate the lifetime and kinetics of both slow-acting (e.g., Ca(2+) oscillations) and fast-acting (e.g., ion conductances, phototransduction) signaling responses. In other cases, RGS proteins integrate G proteins with signaling pathways linked to such diverse cellular responses as cell growth and differentiation, cell motility, and intracellular trafficking. These and other recent studies with animal model systems indicate that RGS proteins play important roles in both physiology and disease. Recognition of the central functions these proteins play in vital cellular processes has focused our attention on RGS proteins as exciting new candidates for therapeutic intervention and drug development.

中文翻译：

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RGS蛋白的细胞调节：G蛋白信号传导的调节剂和整合剂。

G蛋白信号转导（RGS）和RGS样蛋白的调节剂是高度多样化的多功能信号转导蛋白的家族（> 30个成员），它们直接与活化的G alpha亚基结合。家族成员由共享的RGS域定义，该域负责G alpha结合并显着刺激G alpha亚基的GTPase活性，从而导致其失活并终止下游信号。尽管近年来已对RGS / Gα相互作用的生物化学学到了很多知识，但对RGS蛋白的更广泛的细胞作用和调节所知甚少。最新发现表明，共价修饰，替代基因剪接和蛋白质加工等细胞机制可以决定RGS蛋白的活性和亚细胞定位。许多家族成员还直接将G蛋白与越来越多的具有多种细胞作用的信号蛋白连接起来。新发现表明，RGS蛋白不是充当专用抑制剂，而是充当G蛋白信号传导的严格调节剂和整合剂。在某些情况下，RGS蛋白可调节慢作用（例如Ca（2+）振荡）和快作用（例如离子电导，光转导）信号响应的寿命和动力学。在其他情况下，RGS蛋白将G蛋白与信号通路整合在一起，这些信号通路与诸如细胞生长和分化，细胞运动性以及细胞内运输等多种细胞反应相关。这些以及其他有关动物模型系统的研究表明，RGS蛋白在生理和疾病中均起着重要作用。