TY - JOUR
T1 - Minireview
T2 - GPCR and G proteins: Drug efficacy and activation in live cells
AU - Vilardaga, Jean Pierre
AU - Bünemann, Moritz
AU - Feinstein, Timothy N.
AU - Lambert, Nevin
AU - Nikolaev, Viacheslav O.
AU - Engelhardt, Stefan
AU - Lohse, Martin J.
AU - Hoffmann, Carsten
PY - 2009/5
Y1 - 2009/5
N2 - Many biochemical pathways are driven by G protein-coupled receptors, cell surface proteins that convertthe binding of extracellular chemical, sensory, and mechanical stimuli intocellularsignals. 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 Forster 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 atthe level of the receptor by Forster resonance energy transfer is also now possible and allows intrinsic efficacies of clinical drugs to be linked with the effect of receptor polymorphisms.
AB - Many biochemical pathways are driven by G protein-coupled receptors, cell surface proteins that convertthe binding of extracellular chemical, sensory, and mechanical stimuli intocellularsignals. 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 Forster 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 atthe level of the receptor by Forster resonance energy transfer is also now possible and allows intrinsic efficacies of clinical drugs to be linked with the effect of receptor polymorphisms.
UR - http://www.scopus.com/inward/record.url?scp=66649110614&partnerID=8YFLogxK
U2 - 10.1210/me.2008-0204
DO - 10.1210/me.2008-0204
M3 - Short survey
C2 - 19196832
AN - SCOPUS:66649110614
SN - 0888-8809
VL - 23
SP - 590
EP - 599
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 5
ER -