Drexel University College of Medicine, Department of Pharmacology and Physiology, Philadelphia, PA, USA.
Drexel University College of Medicine, Department of Pharmacology and Physiology, Philadelphia, PA, USA.
Cell Signal. 2022 Jun;94:110333. doi: 10.1016/j.cellsig.2022.110333. Epub 2022 Apr 14.
G-protein coupled receptor (GPCR) kinases (GRKs) and β-arrestins play key roles in GPCR and non-GPCR cellular responses. In fact, GRKs and arrestins are involved in a plethora of pathways vital for physiological maintenance of inter- and intracellular communication. Here we review decades of research literature spanning from the discovery, identification of key structural elements, and findings supporting the diverse roles of these proteins in GPCR-mediated pathways. We then describe how GRK2 and β-arrestins partake in non-GPCR signaling and briefly summarize their involvement in various pathologies. We conclude by presenting gaps in knowledge and our prospective on the promising pharmacological potential in targeting these proteins and/or downstream signaling. Future research is warranted and paramount for untangling these novel and promising roles for GRK2 and arrestins in metabolism and disease progression.
G 蛋白偶联受体 (GPCR) 激酶 (GRKs) 和β-arrestin 在 GPCR 和非 GPCR 细胞反应中发挥关键作用。事实上，GRKs 和 arrestin 参与了许多对维持细胞间和细胞内通讯至关重要的途径。在这里，我们回顾了几十年来的研究文献，这些文献涵盖了从发现、关键结构元素的鉴定到支持这些蛋白质在 GPCR 介导途径中发挥多种作用的发现。然后，我们描述了 GRK2 和β-arrestin 如何参与非 GPCR 信号转导，并简要总结了它们在各种疾病中的作用。最后，我们提出了知识空白，并对靶向这些蛋白质和/或下游信号转导的有前途的药理学潜力提出了展望。未来的研究是必要的，对于阐明 GRK2 和 arrestin 在代谢和疾病进展中的这些新的有前途的作用是至关重要的。
