Structure, function, pharmacology and therapeutic potential of the G protein, Gα/q,11

• Main Authors: Danielle eKamato, Lyna eThach, Rebekah eBernard, Vincent eChan, Wenhua eZheng, Harveen eKaur, Margaret eBrimble, Narin eOsman, Peter J Little
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2015-03-01
• Series: Frontiers in Cardiovascular Medicine
• Subjects: cell signalling; G proteins; GPCR; transactivation; therapeutic targets
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fcvm.2015.00014/full

G protein coupled receptors are one of the major classes of cell surface receptors and are associated with a group of G proteins consisting of 3 subunits termed alpha, beta and gamma. G proteins are classified into four families according to their α subunit; Gαi, Gαs, Gα12/13 and Gαq. There are several downstream pathways of Gαq of which the best known is upon activation via GTP, Gαq activates phospholipase Cβ, hydrolysing phosphatidylinositol 4,5-biphosphate into diacylglycerol and inositol triphosphate and activating protein kinase C and increasing calcium efflux from the endoplasmic recticulum. Although G proteins, in particular the Gαq/11 are central elements in GPCR signalling, their actual roles have not yet been thoroughly investigated. The lack of research of the role on Gαq/11 in cell biology is partially due to the obscure nature of the available pharmacological agents. YM-254890 is the most useful Gαq-selective inhibitor with antiplatelet, antithrombotic and thrombolytic effects. YM-254890 inhibits Gαq signalling pathways by preventing the exchange of GDP for GTP. UBO-QIC is a structurally similar compound to YM-254890 which can inhibit platelet aggregation and cause vasorelaxation in rats. Many agents are available for the study of signalling downstream of Gαq/11. The role of G proteins could potentially represents a novel therapeutic target to block all G protein dependent mechanisms. This review will explore the range of pharmacological and molecular tools available for the study of the role of Gαq/11 in GPCR signalling.