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Signal Transduction
Eukaryotes
G Protein-Coupled Receptor (GPCR) Signaling
Seven-transmembrane receptors activating heterotrimeric G proteins.
Overview
GPCRs are the largest family of membrane receptors (~800 in humans). Ligand binding induces conformational change, promoting GDP-to-GTP exchange on the Gα subunit. Gαs activates adenylyl cyclase (cAMP pathway), Gαi inhibits it, Gαq activates PLCβ (IP3/DAG/Ca²⁺ pathway), and Gα12/13 activates Rho GEFs. Signaling is terminated by GTPase activity of Gα and recruitment of arrestins, which also initiate G protein-independent signaling.
Cellular Location
Plasma membrane → Cytoplasm
Clinical Significance
~34% of all FDA-approved drugs target GPCRs; involved in virtually every physiological process; Nobel Prize 2012 (Lefkowitz & Kobilka).