title: Structure, Function, Pharmacology, and Therapeutic Potential of the G Protein, Gα/q,11.
abstract: G protein coupled receptors (GPCRs) are one of the major classes of cell surface receptors and are associated with a group of G proteins consisting of three 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 guanosine triphosphate (GTP), Gαq activates phospholipase Cβ, hydrolyzing phosphatidylinositol 4,5-biphosphate into diacylglycerol and inositol triphosphate and activating protein kinase C and increasing calcium efflux from the endoplasmic reticulum. Although G proteins, in particular, the Gαq/11 are central elements in GPCR signaling, 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 signaling pathways by preventing the exchange of guanosine diphosphate 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 signaling downstream of Gαq/11. The role of G proteins could potentially represent a novel therapeutic target. This review will explore the range of pharmacological and molecular tools available for the study of the role of Gαq/11 in GPCR signaling.
authors.affiliation: Discipline of Pharmacy, Diabetes Complications Group, School of Medical Sciences, Health Innovations Research Institute, RMIT University , Bundoora, VIC , Australia.
authors.forename: Danielle
authors.initials: D
authors.lastname: Kamato
authors.affiliation: Discipline of Pharmacy, Diabetes Complications Group, School of Medical Sciences, Health Innovations Research Institute, RMIT University , Bundoora, VIC , Australia.
authors.forename: Lyna
authors.initials: L
authors.lastname: Thach
authors.affiliation: Discipline of Pharmacy, Diabetes Complications Group, School of Medical Sciences, Health Innovations Research Institute, RMIT University , Bundoora, VIC , Australia.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Bernard
authors.affiliation: Discipline of Pharmacy, Diabetes Complications Group, School of Medical Sciences, Health Innovations Research Institute, RMIT University , Bundoora, VIC , Australia.
authors.forename: Vincent
authors.initials: V
authors.lastname: Chan
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre , Guangzhou , China ; Faculty of Health Sciences, University of Macau , Macau , China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Chemistry, University of Auckland , Auckland , New Zealand.
authors.forename: Harveen
authors.initials: H
authors.lastname: Kaur
authors.affiliation: Department of Chemistry, University of Auckland , Auckland , New Zealand.
authors.forename: Margaret
authors.initials: M
authors.lastname: Brimble
authors.affiliation: Discipline of Pharmacy, Diabetes Complications Group, School of Medical Sciences, Health Innovations Research Institute, RMIT University , Bundoora, VIC , Australia.
authors.forename: Narin
authors.initials: N
authors.lastname: Osman
authors.affiliation: Discipline of Pharmacy, Diabetes Complications Group, School of Medical Sciences, Health Innovations Research Institute, RMIT University , Bundoora, VIC , Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Little
keywords: G proteins; GPCR; cell signaling; therapeutic targets; transactivation