title: GPCR and G proteins: drug efficacy and activation in live cells.
abstract: Many biochemical pathways are driven by G protein-coupled receptors, cell surface proteins that convert the binding of extracellular chemical, sensory, and mechanical stimuli into cellular signals. Their interaction with various ligands triggers receptor activation that typically couples to and activates heterotrimeric G proteins, which in turn control the propagation of secondary messenger molecules (e.g. cAMP) involved in critically important physiological processes (e.g. heart beat). Successful transfer of information from ligand binding events to intracellular signaling cascades involves a dynamic interplay between ligands, receptors, and G proteins. The development of Förster resonance energy transfer and bioluminescence resonance energy transfer-based methods has now permitted the kinetic analysis of initial steps involved in G protein-coupled receptor-mediated signaling in live cells and in systems as diverse as neurotransmitter and hormone signaling. The direct measurement of ligand efficacy at the level of the receptor by Förster resonance energy transfer is also now possible and allows intrinsic efficacies of clinical drugs to be linked with the effect of receptor polymorphisms.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA. jpv@pitt.edu
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vilardaga
authors.forename: Moritz
authors.initials: M
authors.lastname: Bünemann
authors.forename: Timothy N
authors.initials: TN
authors.lastname: Feinstein
authors.forename: Nevin
authors.initials: N
authors.lastname: Lambert
authors.forename: Viacheslav O
authors.initials: VO
authors.lastname: Nikolaev
authors.forename: Stefan
authors.initials: S
authors.lastname: Engelhardt
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lohse
authors.forename: Carsten
authors.initials: C
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D031541:Fluorescence Resonance Energy Transfer; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008163:Luminescent Measurements; D008954:Models, Biological; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins