Heterotrimeric G-protein GTPases

Heterotrimeric G proteins are membrane bound GTPases that are linked to 7-TM receptors. Each G protein contains an α-, β- and γ-subunit and is bound to GDP in the 'off' state. Ligand binding to a 7-TM receptor causes a conformational change in the receptor, which detaches the G protein. This switches the G protein to an 'on' state, allowing GTP to displace GDP, thus G_α can activate second messenger signaling cascades.

There are several types of G_α proteins; G_αs and G_αi bind directly to adenylyl cyclase and stimulate or inhibit its activity, leading to an increase or decrease in cAMP levels respectively. G_αq/11 stimulates PLCβ which catalyzes the hydrolysis of PIP₂ to the second messengers IP₃ and DAG. G_α12/13 are involved in Rho family GTPase signaling. In addition, some G_βγ subunits have active functions; G_βγ coupled to H₁ receptors can activate PLA₂ and G_βγ coupled to M₁ receptors can activate K_IR channels.

Rapid termination of the cellular response is required once the concentration of the stimulating ligand decreases. GTP bound to G_α is hydrolyzed rapidly to GDP, G_α is converted to its inactive form and re-associates with the β- and γ-subunits returning to the 'off' state.

External sources of pharmacological information for Heterotrimeric G-protein GTPases :

• BJP Guide

Heterotrimeric G Protein Gene Data