Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase (GRK)
The RGS domain is found in G protein-coupled receptor kinases (GRKs). These proteins play a key role in phosphorylation-dependent desensitization/resensitization of GPCRs (G protein-coupled receptors), intracellular trafficking, endocytosis, as well as in the modulation of important intracellular signaling cascades by GPCR. GRKs also modulate cellular response in phosphorylation-independent manner using their ability to interact with multiple signaling proteins involved in many essential cellular pathways. 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. Based on sequence homology the GRK family consists of 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). 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.