Regulator of G protein signaling (RGS) proteins are responsible for the rapid turnoff of G protein-coupled receptor signaling pathways. The major mechanism whereby RGS proteins negatively regulate G proteins is via the GTPase activating protein activity of their RGS domain. Structural and mutational analyses have characterized the RGS/G alpha interaction in detail, explaining the molecular mechanisms of the GTPase activating protein activity of RGS proteins.

CCG 2046


An overview of RGS

RGS (a regulator of G-protein signaling) is a recently discovered negative regulator of G-protein signaling transduction with high selectivity and most RGSs play a role through GAPs (GTPase activating proteins). It is tightly regulated in the body. The RGS is a kind of intracellular GTPase-activating proteins (GAPs), and it can accelerate the hydrolysis of GTP, thus limiting the intensity and duration of the activation of GQ and GI proteins and regulating signal transduction processes.

Major types of RGS

So far, the RG has been found widely distributed in protozoa, fungi and mammalian cells. According to the RGS domain homology size, RGS can be divided into nine different subpopulations, including RZ, R4, R7, R12, RA, GEF, GRK, SNX and D-AKAP2.

Inhibition of RGS

CCG-63802 is the reversible selective inhibitor of RGS and is most effective in RGS4. It can accelerate the activity of RGS4 protein by inhibiting GTPase and block its interaction with Gαo. And it can retain activities under reduced conditions.

RGS and diseases

Under normal conditions, the RGS in vivo regulates the G-protein signal transduction system so that the G-protein signal transduction system can respond to the stimulation signals with a certain intensity and duration. If the RGS is abnormal, the regulation of G-protein signal transduction may be abnormal and it may cause tissue damage, which causes the development of diseases. Studies have shown that RGS protein inhibits leukocyte migration induced by chemical chemokines and weakens cell adhesion stimulated by chemical chemokines, indicating that RGS proteins play an extremely important role in the process of leukocyte migration and adhesion induced by chemical chemokines. In addition, RGS proteins are involved in the regulation of cell proliferation and apoptosis. Studies have also shown that RGS3 and RGS4 are GTPase-activated proteins in the heart and RGS4 inhibits the signal transduction of G-protein in cardiomyocytes and can cause increased mortality and myocardial hypertrophy.


1. Yin LL, et al. (2005). Research progress of G-protein signal regulating protein as a new drug target of central nervous system. Chinese Pharmacological Bulletin.