Modeling activation and desensitization of G-protein coupled receptors provides insight into ligand efficacy

Journal of Theoretical Biology

Volumn 200, Issue 2, 1999, Pages 207-222

  Riccobene, Todd A ^a   Omann, Geneva M ^b   Linderman, Jennifer J ^a  

^a UNIVERSITY OF MICHIGAN   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA 2 ADRENERGIC RECEPTOR; DOPAMINE 1 RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; LIGAND; MU OPIATE RECEPTOR; RECEPTOR;

ARTICLE; MATHEMATICAL MODEL; MODEL; PRIORITY JOURNAL; PROTEIN CONFORMATION; RECEPTOR BINDING; RECEPTOR DOWN REGULATION; SIGNAL TRANSDUCTION;

EID: 0033592303     PISSN: 00225193     EISSN: None     Source Type: Journal    
DOI: 10.1006/jtbi.1999.0988     Document Type: Article

References (41)

1. ADAMS J. A., OMANN G. M., LINDERMAN J. J. A mathematical model for ligand/receptor/G-protein dynamics and actin polymerization in human neutrophils. J. theor. Biol. 193:1998;543-560.
2. 1dopamine receptor. J. Neurochem. 55:1990;2111-2116.
3. 1-dopamine receptors linked to adenyl cyclase activity in cultured NS20Y neuroblastoma cells. Mol. Pharm. 38:1990;531-541.
4. BENOVIC J. L., STANISZEWSKI C., MAYOR F., CARON M. G., LEFKOWITZ R. J. β -Adrenergic receptor kinase: activity of partial agonists for stimulation of adenylate cyclase correlates with ability to promote receptor phosphorylation. J. Biol. Chem. 263:1988;3893-3897.
5. BERMAN D. M., GILMAN A. G. Mammalian RGS proteins: barbarians at the gate. J. Biol. Chem. 273:1998;1269-1272.
6. BOKOCH G. M. Chemoattractant signaling and leukocyte activation. Blood. 86:1995;1649-1660.
7. n. J. Cell. Biol. 106:1988;1927-1936.
8. BRAY D. Signaling complexes: biophysical constraints on intracellular communication. Ann. Rev. Biomol. Struct. 27:1998;59-75.
9. CLARK A. J. General pharmacology. Heffner's Handbuch der Experimentellen Pharmakologie Ergaanzunswerk Band 4. 1937;Springer, Berlin.
10. COLEMAN D. E., SPRANG S. R. How G-proteins work: a continuing story. Trends Biochem. Sci. 21:1996;41-44.
11. COLQUHOUN D. Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors. Brit. J. Pharmacol. 125:1998;923-947.
12. CUATRECASAS P. Membrane receptors. Ann Rev. Biochem. 43:1974;169-214.
13. DE LEAN A., STADEL J. M., LEFKOWITZ R. J. A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupledβ -adrenergic receptor. J. Biol. Chem. 255:1980;7108-7117.
14. FREEDMAN N. J., LEFKOWITZ R. J. Desensitization of G-protein-coupled receptors. Rec. Prog. Horm. Res. 51:1996;319-353.
15. HOFFMAN J. F., LINDERMAN J. J., OMANN G. M. Receptor upregulation, internalization, and interconverting receptor states: critical components of a quantitative description of N -formyl peptide receptor dynamics in the neutrophil. J. Biol. Chem. 271:1996a;18 394-18 404.
16. HOFFMAN J. F., KEIL M. L., RICCOBENE T. A., OMANN G. M., LINDERMAN J. J. Interconverting receptor states at 4°C for the neutrophil N -formyl peptide receptor. Biochemistry. 35:1996b;13 047-13 055.
17. HOSEY M. M. Desensitization of muscarinic cholinergic receptors and the role of protein phosphorylation. Sibley D. R., Houslay M. D. Regulation of Signal Transduction Pathways by Desensitization and Amplification. 1994;113-128 Wiley, New York.
18. HYSLOP P. A., SKLAR L. A. A quantitative fluorimetric assay for the determination of oxidant production by ploymorphonuclear leukocytes: Iys use in the simultaneous fluorimetric assay of cellular activation processes. Analyt. Biochem. 141:1984;280-286.
19. 2-Adrenergic receptor desensitization, internalization, and phosphorylation in response to full and partial agonists. J. Biol. Chem. 272:1997;23 871-23 879.
20. KENAKIN T. P. The classification of seven transmembrane receptors in recombinant expression systems. Pharmacol. Rev. 48:1996;413-463.
21. KRUPNICK J. G., BENOVIC J. L. The role of receptor kinases and arrestins in G-protein-coupled receptor regulation. Annu. Rev. Pharmacol. Toxicol. 38:1998;289-319.
22. LEFKOWITZ R. J., COTECCHIA S., SAMAMA P., COSTA T. Constitutive activity of receptors coupled to guanine nucleotide regulatory proteins. Trends Pharmacol. Sci. 14:1993;303-307.
23. 1Adopamine receptor: efficacy in causing desensitization dissociates from both receptor occupancy and functional potency. J. Pharmacol. Exp. Ther. 286:1998;345-353.
24. MODEL M. A., OMANN G. M. Experimental approaches for observing homologous desensitization and their pitfalls. Pharmacol. Res. 37:1998;285-288.
25. NEUBIG R. R., SKLAR L. A. Subsecond modulation of formyl peptide-linked guanine nucleotide-binding proteins by guanosine 5′-o-(3-thio)triphosphate in permeabilized neutophils. Mol. Pharm. 43:1993;734-740.
26. OMANN G. M., ALLEN R. A., BOKOCH G. M., PAINTER R. G., TRAYNOR A. E., SKLAR L. A. Signal transduction and cytoskeletal activation on the neutrophil. Phys. Rev. 67:1987;285-322.
27. PITCHER J. A., INGLESE J., HIGGINS J. B., ARRIZA J. A., CASEY P. J., KIM C., BENOVIC J. L., KWATRA M. M., CARON M. G., LEFKOWITZ R. J. Role of βγ subunits of G-proteins in targeting the β -adrenergic receptor kinase to membrane-bound receptors. Science. 257:1992;1264-1267.
28. POSNER R. G., FAY S. P., DOMALEWSKI M. D., SKLAR L. A. Continuous spectrofluorometric analysis of formyl peptide receptor ternary complex interactions. Mol. Pharm. 45:1994;65-73.
29. PRESS W. H. Numerical Recipes in C, the Art of Scientific Computing. 1992;Cambridge University Press, Cambridge.
30. PROSSNITZ E. R. Desensitization of N -formylpeptide receptor-mediated activation is dependent upon receptor phosphorylation. J. Biol. Chem. 272:1997;15 213-15 219.
31. RICCOBENE T. A. Analysis of G-protein coupled receptor signaling: the relationship between signaling parameters and cellular responses. 1999;University of Michigan.
32. ROUSH W. Regulating G-protein signaling. Science. 271:1996;1056-1058.
33. 2-adrenergic receptor: extending the ternary complex model. J. Biol. Chem. 268:1993;4625-4636.
34. SHEA L. D. Kinetics of ligand, G-protein, and receptor interaction for signal transduction: a modeling study. 1997;University of Michigan.
35. SHEA L. D., LINDERMAN J. J. Mechanistic model of G-protein signal transduction. Determinants of efficacy and effect of precoupled receptors. Biochem. Pharm. 53:1997;519-530.
36. SKLAR L. A., BOKOCH G. M., BUTTON D., SMOLEN J. E. Regulation of ligand-receptor dynamics by guanine nucleotides: real-time analysis of interconverting states for the neutrophil formyl peptide receptor. J. Biol. Chem. 262:1987;135-139.
37. SKLAR L. A., FINNEY D. A., OADES Z. G., JESAITIS A. J., PAINTER R. G., COCHRANE C. G. The dynamics of ligand-receptor interactions. Real-time analyses of association, dissociation, and internalization of an N -formyl peptide and its receptors on the human neutrophil. J. Biol. Chem. 260:1984;11 461-11 467.
38. TOLLEY J. O., OMANN G. M., JESAITIS A. J. A high yield, high purity elutriation method for preparing human granulocytes demonstrating enhanced experimental lifetimes. J. Leukoc. Biol. 42:1987;43-50.
39. TRZECIAKOWSKI J. P. Analysis of stimulus-response chains using nonlinear dynamics. J. Pharm. Tox. Meth. 36:1996;103-121.
40. YU Y., ZHANG L., YIN, XIXI, SUN H., UHL G. R., WANG J. B. μ-Opioid receptor phosphorylation, desensitization, and ligand efficacy. J. Biol. Chem. 272:1997;28 869-28 874.
41. WEISS J. M., MORGAN P. H., LUTZ M. W., KENAKIN T. P. The cubic ternary complex receptor-occupancy model I. Model description. J. theor. Biol. 178:1996;151-167.