The three-component GPCR signaling system is so named based on its ability to recruit and regulate the activity of intracellular ORY-1001 heterotrimeric G proteins. Ligand binding at the extracellular recognition sites on the GPCRs is transduced into intracellular signals through the coupling of the receptor and G protein and between G protein and other effector proteins, all of which can be independently regulated by additional proteins or at the transcriptional level. The heterotrimeric G protein is composed of a, b, and c subunits. The inactive form of the GDP-bound heterotrimeric state is activated when the agonist activated receptor induces a conformational change in the G protein trimer resulting in the Ga-subunit binding to GTP in exchange for GDP. This exchange leads to the Ilaprazole dissociation of Ga-GTP and Gbc subunits that further interact with downstream target effectors thus activating and regulating a signaling cascade. The turnoff of the cellular response occurs when the Ga subunit hydrolyses GTP to GDP and the GaGDP and Gbc subunits re-associate to form the Gabc trimer. The Gb and Gc subunits work as an obligate complex, a functional unit that can only be dissociated under denaturing conditions. The structural and functional aspects of G proteins and their receptor mediated activation have been extensively studied. The third component of the GPCR signaling system is the G proteinregulated effector. Several effectors enhance GTPase activity of the Ga subunit thus playing a role in deactivation and modulation of G protein mediated signaling. A recent modification to the standard model of GPCR signaling has come from a family of proteins called ����regulators of G protein signaling���� or RGS proteins that have been found to accelerate the intrinsic GTPase activity of Ga subunits independent of the Gbc subunits. The modular architecture of the G protein-mediated transmembrane signaling system is highly versatile and specific and is based on the fact that there are numerous receptors and several types of G proteins and effector proteins.