Gproteinmediated

G protein-mediated signaling refers to cellular communication processes initiated by G protein-coupled receptors (GPCRs) that utilize heterotrimeric G proteins to relay extracellular signals to intracellular effectors. In this system, ligand binding to a GPCR promotes exchange of GDP for GTP on the Gα subunit. Gα-GTP then dissociates from the Gβγ dimer, and both components regulate downstream targets.

G proteins are categorized into subfamilies based on their α subunit: Gs, Gi/o, Gq/11, and G12/13. Gs stimulates adenylyl cyclase to increase cyclic AMP (cAMP); Gi inhibits adenylyl cyclase to decrease cAMP; Gq activates phospholipase Cβ, generating inositol trisphosphate (IP3) and diacylglycerol (DAG); G12/13 influences Rho family GTPases through various exchange factors. The resulting second messengers, such as cAMP, IP3, DAG, and Ca2+, propagate signals by activating kinases (e.g., PKA, PKC) and other effectors, leading to diverse cellular responses. Gβγ subunits can also regulate ion channels and kinases, contributing to signaling complexity.

Regulation of G protein signaling involves mechanisms that turn signals off and prevent overactivation. Regulator of G protein signaling (RGS) proteins accelerate GTP hydrolysis on Gα, while receptor desensitization and internalization, often mediated by arrestins, limit GPCR signaling. Some GPCR pathways exhibit signaling bias, preferentially engaging either G protein or beta-arrestin pathways.

Physiologically, G protein-mediated signaling governs vision, olfaction, neurotransmission, heart rate, and many endocrine and metabolic processes. Pharmacologically, many drugs target GPCR signaling by modulating receptors or downstream G protein pathways.