G alpha (z):RGS complex dissociates to give inactive G alpha (z)

Stable Identifier
R-HSA-8982018
Type
Reaction [dissociation]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
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). Subsequently, RGS proteins in the complex facilitate the hydrolysis of GNAZ:GTP to GNAZ:GDP. Following this, the complex dissociates releasing inactive GNAZ ((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
28502923 G-protein-coupled receptor signaling through Gpr176, Gz, and RGS16 tunes time in the center of the circadian clock [Review]

Goto, K, Doi, M, Wang, T, Kunisue, S, Murai, I, Okamura, H

Endocr. J. 2017
12120503 Regulators of G-protein signalling as new central nervous system drug targets

Neubig, RR, Siderovski, DP

Nat Rev Drug Discov 2002
18434541 Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits

Soundararajan, M, Willard, FS, Kimple, AJ, Turnbull, AP, Ball, LJ, Schoch, GA, Gileadi, C, Fedorov, OY, Dowler, EF, Higman, VA, Hutsell, SQ, Sundström, M, Doyle, DA, Siderovski, DP

Proc. Natl. Acad. Sci. U.S.A. 2008
Participants
Participant Of
Orthologous Events
Authored
Reviewed
Created
Cite Us!