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Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 4 (GRK4) The RGS domain is an essential part of the GRK4 (G protein-coupled receptor kinase4) proteins, which are membrane-associated serine/threonine protein kinases that phosphorylate G protein-coupled receptors (GPCRs) upon agonist stimulation. This phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events. GRK4 is a member of the GRK kinase family which includes three major subfamilies: the GRK4 subfamily (GRK4, GRK5 and GRK6), the rhodopsin kinase or visual GRK subfamily (GRK1 and GRK7), and the beta-adrenergic receptor kinases subfamily (GRK2/GRK3). The RGS domain of the GRKs has very little sequence similarity with the canonical RGS domain of the RGS proteins and therefore is often refered to as the RH (RGS Homology) domain. GRK4 plays a key role in regulating dopaminergic-mediated natriuresis and is associated with essential hypertension and/or salt-sensitive hypertension. GRK4 exists in four splice variants involved in hyperphosphorylation, desensitization, and internalization of two dopamine receptors (D1R and D3R). GRK4 also increases the expression of a key receptor of the renin-angiotensin system, the AT1R (angiotensin type 1 receptor). RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",