Regulatory mechanisms involved in modulating RGS function

Abstract

Regulator of G-Protein Signaling (RGS) refers to a conserved 120-125 amino acid motif that was first identified by its ability to negatively regulate G-Protein-Coupled Receptor (GPCR) signalling. Mechanistically, RGSs were found to regulate GPCR responses by binding to and stimulating the GTPase activity of the receptor-activated GTP-bound G alpha subunits. There are now over 25 mammalian RGSs containing proteins that are reported to carry out a variety of functions, many of which are unrelated to GPCR signalling. RGS proteins range in size from small proteins that contain little more than an RGS box to very large proteins that contain a variety of domains. The selectivity of function of the RGS proteins is attributable to the divergence of the RGS sequences as well as the presence of a variety of functional motifs, which allow them to interact with other proteins. Here we focus on the RGSs that are involved in modulating GPCR signalling by reviewing the diversity of the mechanisms involved in regulating these RGSs.

Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice

“…RGS2 modulates stress response signaling by several mechanisms (36,37). First, it inactivates the G αq subunit, which can suppress downstream Ca 2+ -activated cascades (including Cn and CaMKII) and MAPKs (including ERK and JNK), as shown in the current study.…”

Structural Basis for Different Phosphoinositide Specificities of the PX Domains of Sorting Nexins Regulating G-protein Signaling

“…Although we described these proteins in a recent review (3), here we define their relationships in detail based on combined sequence and structural considerations. The first domain upstream of the PX domain is the RGS module, found in a number of molecules that act as GAPs to attenuate GPCR-mediated G-protein signal transduction (7,8). This domain is found in SNX13, SNX14, and SNX25, but not in SNX19 where the corresponding region, although similar in length, shows little sequence homology and has no predicted secondary struc-ture.…”

“…All but SNX19 possess a regulator of G-protein signaling (RGS) domain. RGS domains are small ␣-helical structures that act as GAPs for G␣ subunits of heterotrimeric G-proteins, and thus play critical roles in attenuating G-protein coupled receptor (GPCR) signaling (7,8). SNX13 (also called RGS-PX1) was identified as a specific GAP and regulator of the trimeric G-protein subunit G␣ s involved in cAMP signaling from GPCRs such as the serotonin and ␤-adrenergic receptors (9).…”

Neurobiological Bases of Learning and Their Role for the Paradigm Shift in Education

“…It is noteworthy that GAP only increases the velocity of GTPase activity; the key to the regulation mediated by G proteins consists of a GTPase activity that provides a short and definite activity lapse, since overstimulation generates hyperactivity and can lead to pathological situations such as cancer or dehydration, similar to the toxic effect of the cholera toxin (Jean-Baptiste, Yang, & Greenwood, 2006).…”