G alpha (z) auto-inactivates by hydrolysing GTP to GDP

Stable Identifier
R-HSA-392133
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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When a ligand activates a G protein-coupled receptor, it induces a conformational change in the receptor (a change in shape) that allows the receptor to function as a guanine nucleotide exchange factor (GEF), stimulating the exchange of GDP for GTP on the G alpha subunit. In the traditional view of heterotrimeric protein activation, this exchange triggers the dissociation of the now active G alpha subunit from the beta:gamma dimer, initiating downstream signalling events. The G alpha subunit has intrinsic GTPase activity and will eventually hydrolyze the attached GTP to GDP, allowing reassociation with G beta:gamma. Additional GTPase-activating proteins (GAPs) stimulate the GTPase activity of G alpha, leading to more rapid termination of the transduced signal. In some cases the downstream effector may have GAP activity, helping to deactivate the pathway. This is the case for phospholipase C beta, which possesses GAP activity within its C-terminal region (Kleuss et al. 1994).

Literature References
PubMed ID Title Journal Year
7937899 Mechanism of GTP hydrolysis by G-protein alpha subunits

Kleuss, C, Raw, AS, Lee, E, Sprang, SR, Gilman, AG

Proc Natl Acad Sci U S A 1994
Participants
Participates
Catalyst Activity

GTPase activity of G-protein alpha (z):GTP [plasma membrane]

This event is regulated
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Regulator
Summation

Regulators of G protein signaling (RGS) proteins all contain a 120 amino acid RGS domain that defines the family and enable the protein to bind to active G alpha:GTP. RGS binding greatly increases the intrinsic GTPase activity of G alpha subunits; RGS proteins are GTPase-activating proteins (GAPs) for G alpha. In vitro there is often little or no selectivity for GPCR or G alpha subtype, but in vitro there are marked preferences. Some RGS proteins contain many additional domains and have diverse functions, not limited to modulating GPCR signaling (McCoy & Hepler 2009).

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