Regulators of G protein Signaling (RGS) proteins (version 2020.4) in the IUPHAR/BPS Guide to Pharmacology Database

Abstract

Regulator of G protein Signaling, or RGS, proteins serve an important regulatory role in signaling mediated by G protein-coupled receptors (GPCRs). They all share a common RGS domain that directly interacts with active, GTP-bound Gα subunits of heterotrimeric G proteins. RGS proteins stabilize the transition state for GTP hydrolysis on Gα and thus induce a conformational change in the Gα subunit that accelerates GTP hydrolysis, thereby effectively turning off signaling cascades mediated by GPCRs. This GTPase accelerating protein (GAP) activity is the canonical mechanism of action for RGS proteins, although many also possess additional functions and domains. RGS proteins are divided into four families, R4, R7, R12 and RZ based on sequence homology, domain structure as well as specificity towards Gα subunits. For reviews on RGS proteins and their potential as therapeutic targets, see e.g. [160, 377, 411, 415, 416, 512, 519, 312, 6].

R4 RGS proteins as fine tuners of immature and mature hematopoietic cell trafficking

“…As mentioned in the previous sections, R4 RGS proteins have diverse roles in different cell systems, and each discovery of their dysregulation diseases make them valuable drug target candidates as single‐target drugs or in combination therapies (Table 2). In 2015/2016, R4 RGS proteins have also been added to the International Union of Basic and Clinical Pharmacology/British Pharmacology Society (IUPHAR/BPS), a guide to PHARMACOLOGY database of drug targets (http://www.guidetopharmacology.org), which reflected that much attention has been paid to this class of protein in the area 77,78 . The tissue‐specific expression and interaction on G proteins, targeting these proteins in combination would aid fine‐tuning of the selectivity and efficacy of GPCR‐targeted approaches.…”

“…In 2015/2016, R4 RGS proteins have also been added to the International Union of Basic and Clinical Pharmacology/British Pharmacology Society (IUPHAR/BPS), a guide to PHARMACOLOGY database of drug targets (www.guidetopharmacology.org), which reflected that much attention has been paid to this class of protein in the area. 77,78 The tissuespecific expression and interaction on G proteins, targeting these proteins in combination would aid fine-tuning of the selectivity and efficacy of GPCR-targeted approaches. This strategy possibly reduces adverse side effects by lowering the dose of specific GPCR drugs or enhancing the actions of drugs to improve treatment responses.…”