G alpha (z) in G alpha (z):RGS complex is inactivated

Stable Identifier
R-HSA-8982021
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
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G alpha (z) in G alpha (z):RGS complex is inactivated
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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). Following this, RGS exerts its GAP activity on GNAZ and facilitates the hydrolyses GTP to GDP. This inactivates GNAZ and terminates 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
Participants
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Output
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Catalyst Activity

GTPase activity of G alpha (z):GTP:RGS16,17,20 [plasma membrane]

Physical Entity
G alpha (z):GTP:RGS16,17,20 [plasma membrane] (Homo sapiens)
Activity
GTPase activity (GO:0003924)
Orthologous Events
G alpha (z) in G alpha (z):RGS complex is inactivated (Bos taurus)
G alpha (z) in G alpha (z):RGS complex is inactivated (Caenorhabditis elegans)
G alpha (z) in G alpha (z):RGS complex is inactivated (Canis familiaris)
G alpha (z) in G alpha (z):RGS complex is inactivated (Dictyostelium discoideum)
G alpha (z) in G alpha (z):RGS complex is inactivated (Gallus gallus)
G alpha (z) in G alpha (z):RGS complex is inactivated (Mus musculus)
G alpha (z) in G alpha (z):RGS complex is inactivated (Rattus norvegicus)
G alpha (z) in G alpha (z):RGS complex is inactivated (Saccharomyces cerevisiae)
G alpha (z) in G alpha (z):RGS complex is inactivated (Schizosaccharomyces pombe)
G alpha (z) in G alpha (z):RGS complex is inactivated (Sus scrofa)
G alpha (z) in G alpha (z):RGS complex is inactivated (Xenopus tropicalis)
Authored
Varusai, TM  (2017-07-27)
Reviewed
Siderovski, D  (2018-09-03)
Created
Varusai, TM  (2017-03-15)
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