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8 - Kinetics of GPCR, G protein, and effector activation

from PART III - GPCR SIGNALING FEATURES

Published online by Cambridge University Press:  05 June 2012

Peter Hein
Affiliation:
University of California at San Francisco
Sandra Siehler
Affiliation:
Novartis Institute for Biomedical Research
Graeme Milligan
Affiliation:
University of Glasgow
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Summary

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Chapter
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G Protein-Coupled Receptors
Structure, Signaling, and Physiology
, pp. 145 - 158
Publisher: Cambridge University Press
Print publication year: 2010

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References

Overington, J.P., Al-Lazikani, B., and Hopkins, A.L. (2006). How many drug targets are there?Nat Rev Drug Discov 5, 993–996.CrossRefGoogle Scholar
Cherezov, V., Rosenbaum, D.M., Hanson, M.A., Rasmussen, S.G., Thian, F.S., Kobilka, T.S., Choi, H.J., Kuhn, P., Weis, W.I., Kobilka, B.K., et al. (2007). High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318, 1258–1265.CrossRefGoogle ScholarPubMed
Palczewski, K., Kumasaka, T., Hori, T., Behnke, C.A., Motoshima, H., Fox, B.A., Trong, I., Teller, D.C., Okada, T., Stenkamp, R.E., et al. (2000). Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289, 739–745.CrossRefGoogle ScholarPubMed
Rosenbaum, D.M., Cherezov, V., Hanson, M.A., Rasmussen, S.G., Thian, F.S., Kobilka, T.S., Choi, H.J., Yao, X.J., Weis, W.I., Stevens, R.C., et al. (2007). GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science 318, 1266–1273.CrossRefGoogle ScholarPubMed
Bourne, H.R. (1997). How receptors talk to trimeric G proteins. Curr Opin Cell Biol 9, 134–142.CrossRefGoogle ScholarPubMed
Gilman, A.G. (1987). G proteins: transducers of receptor-generated signals. Annu Rev Biochem 56, 615–649.CrossRefGoogle ScholarPubMed
Tyagi, A., Sethi, A.K., and Chatterji, C. (2002). Comparison of isoprenaline with adrenaline as components of epidural test dose solutions for halothane anaesthetized children. Anaesthesia and intensive care 30, 29–35.Google ScholarPubMed
Gantzos, R.D., and Neubig, R.R. (1988). Temperature effects on a2-adrenergic receptor-Gi interactions. Biochem Pharmacol 37, 2815–2821.CrossRefGoogle Scholar
Biddlecome, G.H., Berstein, G., and Ross, E.M. (1996). Regulation of phospholipase C-b1 by Gq and m1 muscarinic cholinergic receptor. Steady-state balance of receptor-mediated activation and GTPase-activating protein-promoted deactivation. J Biol Chem 271, 7999–8007.CrossRefGoogle Scholar
Makino, C.L., Wen, X.H., and Lem, J. (2003). Piecing together the timetable for visual transduction with transgenic animals. Curr Opin Neurobiol 13, 404–412.CrossRefGoogle ScholarPubMed
Bünemann, M., Bücheler, M.M., Philipp, M., and Hein, L. (2001). Activation and deactivation kinetics of alpha 2A- and alpha 2C-adrenergic receptor-activated G protein-activated inwardly rectifying K+ channel currents. J Biol Chem 276, 47512–47517.CrossRefGoogle Scholar
Bünemann, M., Brandts, B., and Pott, L. (1997). In vivo downregulation of M2 receptors revealed by measurement of muscarinic K+ current in cultured guinea-pig atrial myocytes. J Physiol 501, 549–554.CrossRefGoogle ScholarPubMed
Förster, T. (1948). Zwischenmolekulare Energiewanderung und Fluoreszenz. Ann Phys (Leipzig) 2, 55–75.CrossRefGoogle Scholar
Marullo, S., and Bouvier, M. (2007). Resonance energy transfer approaches in molecular pharmacology and beyond. Trends Pharmacol Sci.CrossRefGoogle ScholarPubMed
Vogel, S.S., Thaler, C., and Koushik, S.V. (2006). Fanciful FRET. Sci STKE 2006, re2.Google ScholarPubMed
Motulsky, H.J., and Mahan, L.C. (1984). The kinetics of competitive radioligand binding predicted by the law of mass action. Mol Pharmacol 25, 1–9.Google ScholarPubMed
Palanche, T., Ilien, B., Zoffmann, S., Reck, M.P., Bucher, B., Edelstein, S.J., and Galzi, J.L. (2001). The neurokinin A receptor activates calcium and cAMP responses through distinct conformational states. J Biol Chem 276, 34853–34861.CrossRefGoogle ScholarPubMed
Castro, M., Nikolaev, V.O., Palm, D., Lohse, M.J., and Vilardaga, J.P. (2005). Turn-on switch in parathyroid hormone receptor by a two-step parathyroid hormone binding mechanism. Proc Natl Acad Sci USA 102, 16084–16089.CrossRefGoogle ScholarPubMed
Gether, U. (2000). Uncovering molecular mechanisms involved in activation of G protein-coupled receptors. Endocr Rev 21, 90–113.CrossRefGoogle ScholarPubMed
Gether, U., Lin, S., and Kobilka, B.K. (1995). Fluorescent labeling of purified beta 2 adrenergic receptor. Evidence for ligand-specific conformational changes. J Biol Chem 270, 28268–28275.Google ScholarPubMed
Swaminath, G., Xiang, Y., Lee, T.W., Steenhuis, J.J., Parnot, C., and Kobilka, B.K. (2004). Sequential binding of agonists to the b2 adrenoceptor. Kinetic evidence for intermediate conformational states. J Biol Chem 279, 686–691.CrossRefGoogle Scholar
Yao, X., Parnot, C., Deupi, X., Ratnala, V.R., Swaminath, G., Farrens, D.L., and Kobilka, B.K. (2006). Coupling ligand structure to specific conformational switches in the β2-adrenoceptor. Nat Chem Bio 2, 417–422.CrossRefGoogle ScholarPubMed
Colquhoun, D., and Sakmann, B. (1981). Fluctuations in the microsecond time range of the current through single acetylcholine receptor ion channels. Nature 294, 464–466.CrossRefGoogle ScholarPubMed
Robert, A., and Howe, J.R. (2003). How AMPA receptor desensitization depends on receptor occupancy. J Neurosci 23, 847–858.CrossRefGoogle ScholarPubMed
Okada, T., Ernst, O.P., Palczewski, K., and Hofmann, K.P. (2001). Activation of rhodopsin: new insights from structural and biochemical studies. Trends Biochem Sci 26, 318–324.CrossRefGoogle ScholarPubMed
Hoffmann, C., Gaietta, G., Bünemann, M., Adams, S.R., Oberdorf-Maass, S., Behr, B., Vilardaga, J.P., Tsien, R.Y., Ellisman, M.H., and Lohse, M.J. (2005). A FlAsH-based FRET approach to determine G protein-coupled receptor activation in living cells. Nat Methods 2, 171–176.CrossRefGoogle ScholarPubMed
Nikolaev, V.O., Hoffmann, C., Bünemann, M., Lohse, M.J., and Vilardaga, J.P. (2006). Molecular basis of partial agonism at the neurotransmitter α2A-adrenergic receptor and Gi-protein heterotrimer. J Biol Chem 281, 24506–24511.CrossRefGoogle ScholarPubMed
Vilardaga, J.P., Bünemann, M., Krasel, C., Castro, M., and Lohse, M.J. (2003). Measurement of the millisecond activation switch of G protein-coupled receptors in living cells. Nat Biotechnol 21, 807–812.CrossRefGoogle ScholarPubMed
Rochais, F., Vilardaga, J.P., Nikolaev, V.O., Bünemann, M., Lohse, M.J., and Engelhardt, S. (2007). Real-time optical recording of beta1-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol. J Clin Invest 117, 229–235.CrossRefGoogle ScholarPubMed
Chachisvilis, M., Zhang, Y.L., and Frangos, J.A. (2006). G protein-coupled receptors sense fluid shear stress in endothelial cells. Proc Natl Acad Sci USA 103, 15463–15468.CrossRefGoogle ScholarPubMed
Zhang, Y., Frangos, J.A., and Chachisvilis, M. (2009). Mechanical stimulus alters conformation of type 1 parathyroid hormone receptor in bone cells. Am J Physiol, Cell Physiol.CrossRefGoogle ScholarPubMed
Marcaggi, P., Mutoh, H., Dimitrov, D., Beato, M., and Knöpfel, T. (2009). Optical measurement of mGluR1 conformational changes reveals fast activation, slow deactivation, and sensitization. Proc Natl Acad Sci USA.CrossRefGoogle ScholarPubMed
Auerbach, A. (2005). Gating of acetylcholine receptor channels: brownian motion across a broad transition state. Proc Natl Acad Sci USA 102, 1408–1412.CrossRefGoogle ScholarPubMed
Macdonald, R.L., and Olsen, R.W. (1994). GABAA receptor channels. Annu Rev Neurosci 17, 569–602.CrossRefGoogle ScholarPubMed
Vilardaga, J.P., Steinmeyer, R., Harms, G.S., and Lohse, M.J. (2005). Molecular basis of inverse agonism in a G protein-coupled receptor. Nat Chem Bio 1, 25.CrossRefGoogle Scholar
Hein, P., and Bünemann, M. (2009). Coupling mode of receptors and G proteins. Naunyn SchmiedebergsArch Pharmacol 379, 435–443.CrossRefGoogle Scholar
Hein, P., Frank, M., Hoffmann, C., Lohse, M.J., and Bünemann, M. (2005). Dynamics of receptor/G protein coupling in living cells. EMBO J 24, 4106–4114.CrossRefGoogle ScholarPubMed
Hein, P., Rochais, F., Hoffmann, C., Dorsch, S., Nikolaev, V.O., Engelhardt, S., Berlot, C.H., Lohse, M.J., and Bünemann, M. (2006). Gs activation is time-limiting in initiating receptor-mediated signaling. J Biol Chem 281, 33345–33351.CrossRefGoogle ScholarPubMed
Gales, C., Rebois, R.V., Hogue, M., Trieu, P., Breit, A., Hebert, T.E., and Bouvier, M. (2005). Real-time monitoring of receptor and G-protein interactions in living cells. Nat Methods 2, 177–184.CrossRefGoogle ScholarPubMed
Gales, C., Durm, J.J., Schaak, S., Pontier, S., Percherancier, Y., Audet, M., Paris, H., and Bouvier, M. (2006). Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes. Nat Struct Biol 13, 778–786.CrossRefGoogle ScholarPubMed
Ernst, O.P., Gramse, V., Kolbe, M., Hofmann, K.P., and Heck, M. (2007). Monomeric G protein-coupled receptor rhodopsin in solution activates its G protein transducin at the diffusion limit. Proc Natl Acad Sci USA 104, 10859–10864.CrossRefGoogle ScholarPubMed
Heck, M., and Hofmann, K.P. (2001). Maximal rate and nucleotide dependence of rhodopsin-catalyzed transducin activation: initial rate analysis based on a double displacement mechanism. J Biol Chem 276, 10000–10009.CrossRefGoogle ScholarPubMed
Bünemann, M., Frank, M., and Lohse, M.J. (2003). Gi protein activation in intact cells involves subunit rearrangement rather than dissociation. Proc Natl Acad Sci USA 100, 16077–16082.CrossRefGoogle ScholarPubMed
Akam, E.C., Carruthers, A.M., Nahorski, S.R., and Challiss, R.A. (1997). Pharmacological characterization of type 1alpha metabotropic glutamate receptor-stimulated [35S]-GTPgammaS binding. Br J Pharmacol 121, 1203–1209.CrossRefGoogle ScholarPubMed
Cowburn, R.F., Wiehager, B., Ravid, R., and Winblad, B. (1996). Acetylcholine muscarinic M2 receptor stimulated [35S]GTP gamma S binding shows regional selective changes in Alzheimer's disease postmortem brain. Neurodegeneration : a journal for neurodegenerative disorders, neuroprotection, and neuroregeneration 5, 19–26.CrossRefGoogle ScholarPubMed
Janetopoulos, C., Jin, T., and Devreotes, P.N. (2001). Receptor-mediated activation of heterotrimeric G-proteins in living cells. Science 291, 2408–2411.CrossRefGoogle ScholarPubMed
Yi, T.M., Kitano, H., and Simon, M.I. (2003). A quantitative characterization of the yeast heterotrimeric G protein cycle. Proc Natl Acad Sci USA 100, 10764–10769.CrossRefGoogle ScholarPubMed
Higashijima, T., Ferguson, K.M., Sternweis, P.C., Smigel, M.D., and Gilman, A.G. (1987). Effects of Mg2+ and the bg-subunit complex on the interactions of guanine nucleotides with G proteins. J Biol Chem 262, 762–766.Google ScholarPubMed
Mukhopadhyay, S., and Ross, E.M. (1999). Rapid GTP binding and hydrolysis by Gq promoted by receptor and GTPase-activating proteins. Proc Natl Acad Sci USA 96, 9539–9544.CrossRefGoogle ScholarPubMed
Fung, B., and Stryer, L. (1980). Photolyzed rhodopsin catalyzes the exchange of GTP for bound GDP in retinal rod outer segments. Proc Natl Acad Sci USA 77, 2500–2504.CrossRefGoogle Scholar
Doupnik, C.A., Davidson, N., Lester, H.A., and Kofuji, P. (1997). RGS proteins reconstitute the rapid gating kinetics of Gbg-activated inwardly rectifying K+ channels. Proc Natl Acad Sci USA 94, 10461–10466.CrossRefGoogle ScholarPubMed
Ross, E.M. (2008). Coordinated Speed and Amplitude in G-Protein Signaling. Curr Biol 18, R777–R783.CrossRefGoogle ScholarPubMed
Adams, S.R., Harootunian, A.T., Buechler, Y.J., Taylor, S.S., and Tsien, R.Y. (1991). Fluorescence ratio imaging of cyclic AMP in single cells. Nature 349, 694–697.CrossRefGoogle ScholarPubMed
Dipilato, L.M., Cheng, X., and Zhang, J. (2004). Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments. Proc Natl Acad Sci USA 101, 16513–16518.CrossRefGoogle ScholarPubMed
Nikolaev, V.O., Bünemann, M., Hein, L., Hannawacker, A., and Lohse, M.J. (2004). Novel Single Chain cAMP Sensors for Receptor-induced Signal Propagation. J Biol Chem 279, 37215–37218.CrossRefGoogle ScholarPubMed
Ponsioen, B., Zhao, J., Riedl, J., Zwartkruis, F., Krogt, G., Zaccolo, M., Moolenaar, W.H., Bos, J.L., and Jalink, K. (2004). Detecting cAMP-induced Epac activation by fluorescence resonance energy transfer: Epac as a novel cAMP indicator. EMBO Rep 5, 1176–1180.CrossRefGoogle ScholarPubMed
Zaccolo, M., De Giorgi, F., Cho, C.Y., Feng, L., Knapp, T., Negulescu, P.A., Taylor, S.S., Tsien, R.Y., and Pozzan, T. (2000). A genetically encoded, fluorescent indicator for cyclic AMP in living cells. Nat Cell Biol 2, 25–29.CrossRefGoogle ScholarPubMed
Nikolaev, V.O., Gambaryan, S., Engelhardt, S., Walter, U., and Lohse, M.J. (2005). Real-time Monitoring of the PDE2 Activity of Live Cells: hormone-stimulated cAMP hydrolysis is faster than hormone-stimulated cAMP synthesis. J Biol Chem 280, 1716–1719.CrossRefGoogle ScholarPubMed
Benians, A., Leaney, J.L., Milligan, G., and Tinker, A. (2003). The dynamics of formation and action of the ternary complex revealed in living cells using a G-protein-gated K+ channel as a biosensor. J Biol Chem 278, 10851–10858.CrossRefGoogle ScholarPubMed
Benians, A., Nobles, M., Hosny, S., and Tinker, A. (2005). Regulators of G-protein signaling form a quaternary complex with the agonist, receptor, and G-protein. A novel explanation for the acceleration of signaling activation kinetics. J Biol Chem 280, 13383–13394.CrossRefGoogle Scholar
Lober, R.M., Pereira, M.A., and Lambert, N.A. (2006). Rapid activation of inwardly rectifying potassium channels by immobile G-protein-coupled receptors. J Neurosci 26, 12602–12608.CrossRefGoogle ScholarPubMed
Bünemann, M., and Pott, L. (1995). Down-regulation of A1 adenosine receptors coupled to muscarinic K+ current in cultured guinea-pig atrial myocytes. J Physiol (Lond) 482 (Pt 1), 81–92.CrossRefGoogle ScholarPubMed
Wellner-Kienitz, M.C., Bender, K., Meyer, T., Bünemann, M., and Pott, L. (2000). Overexpressed A(1) adenosine receptors reduce activation of acetylcholine-sensitive K(+) current by native muscarinic M(2) receptors in rat atrial myocytes. Circ Res 86, 643–648.CrossRefGoogle ScholarPubMed
Bünemann, M., Brandts, B., and Pott, L. (1996). Downregulation of muscarinic M2 receptors linked to K+ current in cultured guinea-pig atrial myocytes. J Physiol 494, 351–362.CrossRefGoogle Scholar
Hall, R.A., Premont, R.T., and Lefkowitz, R.J. (1999). Heptahelical receptor signaling: beyond the G protein paradigm. The Journal of cell biology 145, 927–932.CrossRefGoogle ScholarPubMed
DeWire, S.M., Ahn, S., Lefkowitz, R.J., and Shenoy, S.K. (2007). Beta-arrestins and cell signaling. Annu Rev Physiol 69, 483–510.CrossRefGoogle ScholarPubMed
Ahn, S., Shenoy, S.K., Wei, H., and Lefkowitz, R.J. (2004). Differential kinetic and spatial patterns of beta-arrestin and G protein-mediated ERK activation by the angiotensin II receptor. J Biol Chem 279, 35518–35525.CrossRefGoogle Scholar
Gesty-Palmer, D., Chen, M., Reiter, E., Ahn, S., Nelson, C.D., Wang, S., Eckhardt, A.E., Cowan, C.L., Spurney, R.F., Luttrell, L.M., et al. (2006). Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation. J Biol Chem 281, 10856–10864.CrossRefGoogle Scholar
Krasel, C., Bünemann, M., Lorenz, K., and Lohse, M.J. (2005). b-Arrestin Binding to the b2-Adrenergic Receptor Requires Both Receptor Phosphorylation and Receptor Activation. J Biol Chem 280, 9528–9535.CrossRefGoogle Scholar
Violin, J.D., Ren, X.R., and Lefkowitz, R.J. (2006). G-protein-coupled receptor kinase specificity for β-arrestin recruitment to the β2-adrenergic receptor revealed by fluorescence resonance energy transfer. J Biol Chem 281, 20577–20588.CrossRefGoogle ScholarPubMed
Tran, T.M., Friedman, J., Qunaibi, E., Baameur, F., Moore, R.H., and Clark, R.B. (2004). Characterization of agonist stimulation of cAMP-dependent protein kinase and G protein-coupled receptor kinase phosphorylation of the b2-adrenergic receptor using phosphoserine-specific antibodies. Mol Pharmacol 65, 196–206.CrossRefGoogle Scholar
Nikolaev, V.O., and Lohse, M.J. (2006). Monitoring of cAMP synthesis and degradation in living cells. Physiology 21, 86–92.CrossRefGoogle ScholarPubMed

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