Reactome | Active G alpha (z) binds RGS proteins

Active G alpha (z) binds RGS proteins

Stable Identifier

R-HSA-8981892

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

G Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G proteins). Upon activation, GPCRs can replace the GDP with GTP in the alpha subunit of G proteins. GTP binding modifies the conformation of G alpha proteins and activates them. The Regulator of G protein Signalling (RGS) are GTPase Accelerating Proteins (GAPs) that can directly inhibit the G alpha subunit activity. There are at least 25 different types of RGS proteins known. RGS16, RGS17 and RGS20 can bind and stabilize the transition state of Guanine nucleotide binding protein G(z) subunit alpha (GNAZ) along its path to GTP hydrolysis. Subsequently, this leads to GTP hydrolysis and inactivation of GNAZ, terminating downstream signalling (Neubig & Siderovski 2002, Kach et al. 2012, Goto K et al. 2017). GNAZ inhibits adenylyl cyclase and interacts with Rap1GAP to attenuate Rap1 signaling.

Literature References

PubMed ID	Title	Journal	Year
12120503	Regulators of G-protein signalling as new central nervous system drug targets Neubig, RR, Siderovski, DP	Nat Rev Drug Discov	2002
28502923	G-protein-coupled receptor signaling through Gpr176, Gz, and RGS16 tunes time in the center of the circadian clock [Review] Wang, T, Doi, M, Murai, I, Goto, K, Kunisue, S, Okamura, H	Endocr. J.	2017
18434541	Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits Kimple, AJ, Dowler, EF, Ball, LJ, Hutsell, SQ, Willard, FS, Soundararajan, M, Gileadi, C, Doyle, DA, Turnbull, AP, Higman, VA, Siderovski, DP, Schoch, GA, Fedorov, OY, Sundström, M	Proc. Natl. Acad. Sci. U.S.A.	2008