Functional signaling biases in G protein-coupled receptors: Game theory and receptor dynamics

Mini-Reviews in Medicinal Chemistry

Volumn 12, Issue 9, 2012, Pages 831-840

  Maudsley, S ^a   Patel, S A ^a,b   Park, S S ^a   Luttrell, L M ^c   Martin, B ^a  

^a NATIONAL INSTITUTE ON AGING   (United States)

^b Baltimore County   (United States)

^c MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

Aging; Allostasis; Biased agonist; Drug design; G protein coupled receptor; Signaling

Indexed keywords

ADRENERGIC RECEPTOR; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; CANNABINOID; CATECHOLAMINE; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR AGONIST; NORADRENALIN; PARATHYROID HORMONE RECEPTOR; PHOSPHODIESTERASE; PROLINE RICH PROTEIN; PROTEIN TYROSINE KINASE; RETINA S ANTIGEN; SEROTONIN; SYNTROPHIN; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG;

AGING; ARTICLE; CONGESTIVE HEART FAILURE; DRUG SYNTHESIS; DRUG TARGETING; HEART OUTPUT; HEART VENTRICLE FUNCTION; HOMEOSTASIS; HYPOTENSION; NEUROMUSCULAR SYNAPSE; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN PROTEIN INTERACTION; SARCOLEMMA; SIGNAL TRANSDUCTION;

BIOLOGICAL AGENTS; DRUG DESIGN; FEEDBACK, PHYSIOLOGICAL; GAME THEORY; HUMANS; LIGANDS; MOLECULAR TARGETED THERAPY; PROTEIN CONFORMATION; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION;

EID: 84862876092     PISSN: 13895575     EISSN: 18755607     Source Type: Journal    
DOI: 10.2174/138955712800959071     Document Type: Article

References (77)

1. Lagerström, M.C.; Schiöth, H.B. Structural diversity of G proteincoupled receptors and significance for drug discovery. Nat. Rev. Drug Discov. 2008, 7(4), 339-357.
2. Chadwick, W.A.; Maudsley, S. Hormesis: A revolution in biology, toxicology and medicine, 1st ed,; Springer Science: New York, 2010.
3. Maudsley, S.; Martin, B.; Luttrell, L.M. The origins of diversity and specificity in g protein-coupled receptor signaling. J. Pharmacol. Exp. Ther. 2005, 314(2), 485-494.
4. Karlin, A. On the application of a plausible model of allosteric proteins to the receptor for acetylcholine. J. Theor. Biol. 1967, 16(2), 306-320.
5. De Lean, A.; Stadel, J.M.; Lefkowitz, R.J. A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor. J. Biol. Chem. 1980, 255(15), 7108-7117.
6. Kjelsberg, M.A.; Cotecchia, S.; Ostrowski, J.; Caron, M.G.; Lefkowitz, R.J. Constitutive activation of the alpha 1B-adrenergic receptor by all amino acid substitutions at a single site. Evidence for a region which constrains receptor activation. J. Biol. Chem. 1992, 267(3), 1430-1433.
7. Samama, P.; Pei, G.; Costa, T.; Cotecchia, S.; Lefkowitz, R.J. Negative antagonists promote an inactive conformation of the beta 2-adrenergic receptor. Mol. Pharmacol. 1994, 45(3), 390-394.
8. Donnelly, D.; Maudsley, S.; Gent, J.P.; Moser, R.N.; Hurrell, C.R.; Findlay, J.B. Conserved polar residues in the transmembrane domain of the human tachykinin NK2 receptor: functional roles and structural implications. Biochem. J. 1999, 339(1), 55-61.
9. Lefkowitz, R.J.; Cotecchia, S.; Samama, P.; Costa, T. Constitutive activity of receptors coupled to guanine nucleotide regulatory proteins. Trends Pharmacol. Sci. 1993, 14(8), 303-307.
10. Kenakin, T. Pharmacological proteus? Trends Pharmacol. Sci. 1995, 16(8), 256-258.
11. Kenakin, T. Agonist-receptor efficacy II. Agonist trafficking of receptor signals. Trends Pharmacol. Sci. 1995, 16(7), 232-238.
12. Kenakin, T. Functional selectivity through protean and biased agonism.: who steers the ship? Mol. Pharmacol. 2007, 72(6), 1393-1401.
13. Kenakin, T. Functional selectivity and biased receptor signaling. J. Pharmacol. Exp. Ther. 2011, 336(2), 296-302.
14. Urban, J.D.; Clarke, W.P.; von Zastrow, M.; Nichols, D.E.; Kobilka, B.; Weinstein, H.; Javitch, J.A.; Roth, B.L.; Christopoulos, A.; Sexton, P.M.; Miller, K.J.; Spedding, M.; Mailman, R.B. Functional selectivity and classical concepts of quantitative pharmacology. J. Pharmacol. Exp. Ther. 2007, 320(1), 1-13.
15. Bonhaus, D.W.; Chang, L.K.; Kwan, J.; Martin, G.R., Dual activation and inhibition of adenylyl cyclase by cannabinoid receptor agonists: evidence for agonist-specific trafficking of intracellular responses. J. Pharmacol. Exp. Ther., 1998, 287(3), 884-888.
16. Kukkonen, J.P.; Jansson, C.C.; Akerman, K.E., Agonist trafficking of G(i/o)-mediated alpha(2A)-adrenoceptor responses in HEL 92.1.7 cells. Br. J. Pharmacol., 2001, 132(7), 1477-1484.
17. Berg, K.A.; Maayani, S.; Goldfarb, J.; Scaramellini, C.; Leff, P.; Clarke, W.P., Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus. Mol. Pharmacol., 1998, 54(1), 94-104.
18. Eason, M.G.; Jacinto, M.T.; Liggett, S.B., Contribution of ligand structure to activation of alpha 2-adrenergic receptor subtype coupling to Gs. Mol. Pharmacol., 1994, 45(4), 696-702.
19. Berg, K.A.; Maayani, S.; Goldfarb, J.; Clarke, W.P., Pleiotropic behavior of 5-HT2A and 5-HT2C receptor agonists. Ann. N. Y. Acad. Sci., 1998, 861, 104-110.
20. Seifert, R.; Wenzel-Seifert, K.; Gether, U.; Kobilka, B.K. Functional differences between full and partial agonists: evidence for ligand-specific receptor conformations. J. Pharmacol. Exp. Ther. 2001, 297(3), 1218-1226.
21. Seifert, R.; Gether, U.; Wenzel-Seifert, K.; Kobilka, B.K. Effects of guanine, inosine, and xanthine nucleotides on beta(2)-adrenergic receptor/G(s) interactions: evidence for multiple receptor conformations. Mol. Pharmacol. 1999, 56(2), 348-358.
22. Maudsley, S.; Davidson, L.; Pawson, A.J.; Chan, R.; López de Maturana, R.; Millar, R.P. Gonadotropin-releasing hormone (GnRH) antagonists promote proapoptotic signaling in peripheral reproductive tumor cells by activating a Galphai-coupling state of the type I GnRH receptor. Cancer Res. 2004, 64(20), 7533-7544.
23. Ahmed, I.; Gesty-Palmer, D.; Drezner, M.K.; Luttrell, L.M. Transactivation of the epidermal growth factor receptor mediates parathyroid hormone and prostaglandin F2 alpha-stimulated mitogen-activated protein kinase activation in cultured transgenic murine osteoblasts. Mol. Endocrinol. 2003, 17(8), 1607-1621.
24. Nickl, K.; Gardner, E.E.; Geiger, S.; Heilmann, J.; Seifert, R. Differential coupling of the human cannabinoid receptors hCB1R and hCB2R to the G-protein G(alpha)i2beta1gamma2. Neurosci. Lett. 2008, 447(1), 68-72.
25. Cordeaux, Y.; Ijzerman, A.P.; Hill, S.J. Coupling of the human A1 adenosine receptor to different heterotrimeric G proteins: evidence for agonist-specific G protein activation. Br. J. Pharmacol. 2004, 143(6), 705-714.
26. Luttrell, L.M.; Ferguson, S.S.; Daaka, Y.; Miller, W.E.; Maudsley, S.; Della Rocca, G.J.; Lin, F.; Kawakatsu, H.; Owada, K.; Luttrell, D.K.; Caron, M.G.; Lefkowitz, R.J. Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science 1999, 283(5402), 655-661.
27. DeFea, K.A.; Zalevsky, J.; Thoma, M.S.; Déry, O.; Mullins, R.D.; Bunnett, N.W. Beta-arrestin-dependent endocytosis of proteinaseactivated receptor 2 is required for intracellular targeting of activated ERK1/2. J. Cell Biol. 2000, 148(6), 1267-1281.
28. Tohgo, A.; Pierce, K.L.; Choy, E.W.; Lefkowitz, R.J.; Luttrell, L.M. Beta-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK activity but inhibits ERK-mediated transcription following angiotensin AT1a receptor stimulation. J. Biol. Chem. 2002, 277(11), 9429-9436.
29. Gesty-Palmer, D.; Flannery, P.; Yuan, L.; Corsino, L.; Spurney, R.; Lefkowitz, R.J.; Luttrell, L.M. A beta-arrestin-biased agonist of the parathyroid hormone receptor (PTH1R) promotes bone formation independent of G protein activation. Sci. Transl. Med. 2009, 1(1), 1-10.
30. Andresen B.T.; Luttrell L.M. Brave new world? Arrestin pathway bias in drug design. Endocr. Metab. Immune Disord. Drug Targets 2011, 11(2), 90-91.
31. Gesty-Palmer, D.; Luttrell, L.M. 'Biasing' the parathyroid hormone receptor: A novel anabolic approach to increasing bone mass? Br. J. Pharmacol. 2011, 164(1), 59-67.
32. Luttrell, L.M.; Gesty-Palmer, D. Beyond desensitization: physiological relevance of arrestin-dependent signaling. Pharmacol. Rev. 2010, 62(2), 305-330.
33. Shenoy, S.K.; McDonald, P.H.; Kohout, T.A.; Lefkowitz, R.J. Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin. Science 2001, 294(5545), 1307-1313.
34. Nelson, C.D.; Perry, S.J.; Regier, D.S.; Prescott, S.M.; Topham, M.K.; Lefkowitz, R.J. Targeting of diacylglycerol degradation to M1 muscarinic receptors by beta-arrestins. Science 2007, 315(5812), 663-666.
35. Perry, S.J.; Baillie, G.S.; Kohout, T.A.; McPhee, I.; Magiera, M.M.; Ang, K.L.; Miller, W.E.; McLean, A.J.; Conti, M.; Houslay, M.D.; Lefkowitz, R.J. Targeting of cyclic AMP degradation to beta 2- adrenergic receptors by beta-arrestins. Science 2002, 298(5594), 834-836.
36. Sun, J.; Lin, X. Beta-arrestin 2 is required for lysophosphatidic acid-induced NF-kappaB activation. Proc. Natl. Acad. Sci. U S A. 2008, 105(44), 17085-17090.
37. Beaulieu, J.M.; Sotnikova, T.D.; Marion, S.; Lefkowitz, R.J.; Gainetdinov, R.R.; Caron, M.G. An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell 2005, 122(2), 261-273.
38. Hall, R.A.; Premont, R.T.; Chow, C.W.; Blitzer, J.T.; Pitcher, J.A.; Claing, A.; Stoffel, R.H.; Barak, L.S.; Shenolikar, S.; Weinman, E.J.; Grinstein, S.; Lefkowitz, R.J. The beta2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange. Nature 1998, 392(6676), 626-630.
39. Maudsley, S.; Zamah, A.M.; Rahman, N.; Blitzer, J.T.; Luttrell, L.M.; Lefkowitz, R.J.; Hall, R.A. Platelet-derived growth factor receptor association with Na(+)/H(+) exchanger regulatory factor potentiates receptor activity. Mol. Cell Biol. 2000, 20(22), 8352-8363.
40. McLatchie, L.M.; Fraser, N.J.; Main, M.J.; Wise, A.; Brown, J.; Thompson, N.; Solari, R.; Lee, M.G.; Foord, S.M. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 1998, 393(6683), 333-339.
41. Maudsley, S.; Naor, Z.; Bonfil, D.; Davidson, L.; Karali, D.; Pawson, A.J.; Larder, R.; Pope, C.; Nelson, N.; Millar, R.P.; Brown, P. Proline-rich tyrosine kinase 2 mediates gonadotropinreleasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene. Mol. Endocrinol. 2007, 21(5), 1216-1233.
42. Davidson, L.; Pawson, A.J.; López de Maturana, R.; Freestone, S.H.; Barran, P.; Millar, R.P.; Maudsley, S. Gonadotropin-releasing hormone-induced activation of diacylglycerol kinase-zeta and its association with active c-Src. J. Biol. Chem. 2004, 279(12), 11906-11916.
43. González-Maeso, J.; Ang, R.L.; Yuen, T.; Chan, P.; Weisstaub, N.V.; López-Giménez, J.F.; Zhou, M.; Okawa, Y.; Callado, L.F.; Milligan, G.; Gingrich, J.A.; Filizola, M.; Meana, J.J.; Sealfon, S.C. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 2008, 452(7183), 93-97.
44. Maudsley, S.; Davidson, L.; Pawson, A.J.; Freestone, S.H.; López de Maturana, R.; Thomson, A.A.; Millar, R.P. Gonadotropinreleasing hormone functionally antagonizes testosterone activation of the human androgen receptor in prostate cells through focal adhesion complexes involving Hic-5. Neuroendocrinology 2006, 84(5), 285-300.
45. Ritter, S.L.; Hall, R.A. Fine-tuning of GPCR activity by receptorinteracting proteins. Nat. Rev. Mol. Cell Biol. 2009, 10(12), 819-830.
46. Luttrell, L.M. Reviews in molecular biology and biotechnology: transmembrane signaling by G protein-coupled receptors. Mol. Biotechnol. 2008, 39(3), 239-264
47. Luttrell, L.M. Composition and function of G protein-coupled receptor signalsomes controlling mitogen-activated protein kinase activity. J. Mol. Neurosci. 2005, 26(2-3), 253-264.
48. Maudsley, S.; Martin, B.; Luttrell, L.M. G protein-coupled receptor signaling complexity in neuronal tissue: implications for novel therapeutics. Curr. Alzheimer Res. 2007, 4(1), 3-19.
49. Martin, B.; Brenneman, R.; Golden, E.; Walent, T.; Becker, K.G.; Prabhu, V.V.; Wood, W. 3rd; Ladenheim, B.; Cadet, J.L.; Maudsley, S. Growth factor signals in neural cells: coherent patterns of interaction control multiple levels of molecular and phenotypic responses. J. Biol. Chem. 2009, 284(4), 2493-2511.
50. Ferguson, S.S. Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol. Rev. 2001, 53(1), 1-24.
51. McEwen, B.S. Stress, adaptation, and disease. Allostasis and allostatic load. Ann. N. Y. Acad. Sci. 1998, 840, 33-44.
52. McEwen, B.S.; Wingfield, J.C. The concept of allostasis in biology and biomedicine. Horm. Behav. 2003, 43(1), 2-15.
53. Chadwick, W.; Zhou, Y.; Park, S.S.; Wang, L.; Mitchell, N.; Stone, M.D.; Becker, K.G.; Martin, B.; Maudsley, S. Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010, 5(12), e14352.
54. Grassi, G.; Seravalle, G.; Quarti-Trevano, F.; Dell'oro, R. Sympathetic activation in congestive heart failure: evidence, consequences and therapeutic implications. Curr. Vasc. Pharmacol. 2009 7(2), 137-145.
55. Hamdani, N.; de Waard, M.; Messer, A.E.; Boontje, N.M.; Kooij, V.; van Dijk, S.; Versteilen, A.; Lamberts, R.; Merkus, D.; Dos Remedios, C.; Duncker, D.J.; Borbely, A.; Papp, Z.; Paulus, W.; Stienen, G.J.; Marston, S.B.; van der Velden, J. Myofilament dysfunction in cardiac disease from mice to men. J. Muscle Res. Cell Motil. 2008 29(6-8), 189-201.
56. Lymperopoulos, A.; Rengo, G.; Koch, W.J. Adrenal adrenoceptors in heart failure: fine-tuning cardiac stimulation. Trends Mol. Med. 2007 13(12), 503-511.
57. Ungerer, M.; Bohm, M.; Elce, J.S.; Erdmann, E.; Lohse, M.J. Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart. Circulation 1993 87, 454-463.
58. Xiang, Y.; Kobilka, B.K. Myocyte adrenoceptor signaling pathways. Science 2003, 300, 1530-1532.
59. Noma, T.; Lemaire, A.; Naga Prasad, S.V.; Barki-Harrington, L.; Tilley, D.G.; Chen, J.; Le Corvoisier, P.; Violin, J.D.; Wei, H.; Lefkowitz, R.J.; Rockman, H.A. Beta-arrestin-mediated beta1- adrenergic receptor transactivation of the EGFR confers cardioprotection. J. Clin. Invest. 2007, 117, 2445-2458.
60. Lyssand, J.S.; DeFino, M.C.; Tang, X.B.; Hertz, A.L.; Feller, D.B.; Wacker, J.L.; Adams, M.E.; Hague, C. Blood pressure is regulated by an alpha1D-adrenergic receptor/dystrophin signalosome. J. Biol. Chem. 2008 283(27), 18792-18800.
61. Lyssand, J.S.; Lee, K.S.; Defino, M.; Adams, M.E.; Hague, C. Syntrophin isoforms play specific functional roles in the (1D)-adrenergic receptor/DAPC signalosome. Biochem. Biophys. Res. Commun. 2011 [Epub ahead of print]
62. Cartaud, A.; Stetzkowski-Marden, F.; Cartaud, J. Identification of dystrophin-binding protein(s) in membranes from Torpedo electrocyte and rat muscle. J. Biol. Chem. 1993, 268(18), 13019-13022.
63. Suzuki, A.; Yoshida, M.; Ozawa, E. Mammalian alpha 1- and beta 1-syntrophin bind to the alternative splice-prone region of the dystrophin COOH terminus. J. Cell. Biol. 1995, 128(3), 373-381.
64. Kramarcy, N.R.; Vidal, A.; Froehner, S.C.; Sealock, R. Association of utrophin and multiple dystrophin short forms with the mammalian M(r) 58,000 dystrophin-associated protein (syntrophin). J. Biol. Chem. 1994, 269(4), 2870-2876.
65. Ahn, A.H.; Kunkel, L.M. Syntrophin binds to an alternatively spliced exon of dystrophin. J. Cell Biol. 1995, 128(3), 363-371.
66. Adams, M.E.; Butler, M.H.; Dwyer, T.M.; Peters, M.F.; Murnane, A.A.; Froehner, S.C. Two forms of mouse syntrophin, a 58 kd dystrophin-associated protein, differ in primary structure and tissue distribution. Neuron 1993, 11(3), 531-540.
67. Ahn, A.H.; Yoshida, M.; Anderson, M.S.; Feener, C.A.; Selig, S.; Hagiwara, Y.; Ozawa, E.; Kunkel, L.M. Cloning of human basic A1, a distinct 59-kDa dystrophin-associated protein encoded on chromosome 8q23-24. Proc. Natl. Acad. Sci. U S A 1994, 91(10), 4446-4450.
68. Piluso, G.; Mirabella, M.; Ricci, E.; Belsito, A.; Abbondanza, C.; Servidei, S.; Puca, A.A.; Tonali, P.; Puca, G.A.; Nigro, V. Gamma1- and gamma2-syntrophins, two novel dystrophin-binding proteins localized in neuronal cells. J. Biol. Chem. 2000, 275(21), 15851-15860.
69. Kostin, S.; Hein, S.; Arnon, E.; Scholz, D.; Schaper, J. The cytoskeleton and related proteins in the human failing heart. Heart. Fail. Rev. 2000 5(3), 271-280.
70. Kawada, T.; Masui, F.; Tezuka, A.; Ebisawa, T.; Kumagai, H.; Nakazawa, M.; Toyo-Oka, T. A novel scheme of dystrophin disruption for the progression of advanced heart failure. Biochim. Biophys. Acta. 2005 1751(1), 73-81.
71. Finsterer, J.; Stöllberger, C. The heart in human dystrophinopathies. Cardiology 2003 99(1), 1-19.
72. Myerson, R.B. Game theory: analysis of conflict, 1st ed.; Harvard University Press, 1991.
73. Smith, J.M; Price, G.R. The logic of animal conflict. Nature 1973, 246(5427), 15-18.
74. Christodoulou, C.; Banfield, G.; Cleanthous, A. Self-control with spiking and non-spiking neural networks playing games. J. Physiol. Paris 2010, 104(3-4), 108-117.
75. Smith, J.M. Evolution and the Thoery of Games, 1st ed.; Cambridge University Press, 1981.
76. Flegal, K.M.; Carroll, M.D.; Ogden, C.L.; Curtin, L.R. Prevalence and trends in obesity among US adults, 1999-2008. JAMA 2010, 303, 235-241
77. Miniño, A.M.; Xu, J.; Kochanek, K.D.; Tejada-Vera, B. Death in the United States, 2007. NCHS Data Brief 2009, 26, 1-8.