G-Protein Signaling

G proteins are heterotrimeric GTP-binding signaling proteins and are composed of α, β and γ subunits encoded by distinct genes. Bound to the intracellular face of G-protein coupled receptors (GPCRs), G-proteins mediate cytoplasmic transduction of extracellular stimuli. The α subunit is responsible for the binding of GDP and GTP. Binding of a ligand to the GPCR results in a transition of GDP-bound to a GTP-bound α subunit and leads to the activation of the heterotrimer through dissociation of the α-GTP from the βγ dimer. Both the α-GTP and the βγ dimer regulate the activities of a variety of effectors that transmit signals to the cell interior through the production of second messenger molecules (eg, calcium, cAMP, etc). There are at least 17 Gα genes grouped into five main classes termed Gi/o, Gq, Gs and G12. GPCRs can couple to a variety of G proteins, leading to activation of many complex signaling pathways upon ligand binding, including gated channels, adenylyl cyclase and many other critical second messenger cascades.