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Principles and Methods in Receptor Binding pp 233–253Cite as

Structure-Function Relations for Cell Surface Receptors and Adenylate Cyclase: Studies Using Target Size Analysis of Radiation Inactivation

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Part of the book series: NATO ASI Series ((NSSA,volume 72))

Abstract

Understanding the functioning of a cell surface receptor is possible only with knowledge about its structure. A priori receptors are likely to be complex since many functions have to be accomodated. A receptor recognizes a particular substance or class of substances with great precision in a sea of similar substances, binds it, generates a signal by triggering contacting enzyme systems or by regulation of ion channels, terminates the signal, and is subjected to various modulations by “nonspecific” ligands like GTP, ions, and phospholipids, or by the specific ligands, i. e. in the instance of desensitization. In a first approach to structural analysis the question is asked what structure is responsible for a particular partial function of the receptor. Several methods have been applied to the study of structurefunction relationships of cell surface receptors:

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References

  1. Y. Citri and M. Schramm, Resolution, reconstitution and kinetics of the primary action of a hormone receptor, Nature 287: 297 (1980).

    Article  PubMed  CAS  Google Scholar 

  2. J. Orly and M. Schramm, Coupling of catecholamine receptor from one cell with adenylate cyclase from another cell by cell fusion, Proc. Nat. Acad. Sci. 73: 4410 (1976).

    Article  PubMed  CAS  Google Scholar 

  3. H. R. Bourne, P. Coffino, and G.M. Tomkins, Selection of a variant lymphoma cell deficient in adenylate cyclase, Science 187: 750 (1975).

    Article  PubMed  CAS  Google Scholar 

  4. P. C. Sternweis, J. K. Northup, M. D. Smigel, and A. G. Gilman, The regulatory component of adenylate cyclase. Purification and properties, J. Biol. Chem. 256: 11517 (1961).

    Google Scholar 

  5. E. Hanski, P. C. Sternweis, J. K. Northup, A. W. Dromerick, and A. G. Gilman, The regulatory component of adenylate cyclase. Purification and properties of the turkey erythrocyte protein, J. Biol. Chem. 256: 12911 (1981).

    PubMed  CAS  Google Scholar 

  6. D. E. Lea, Actions of radiation on living cells, Cambridge University Press, London (1955).

    Google Scholar 

  7. G. R. Kepner and R. I. Macey, Membrane enzyme systems. Molecular size determinations by radiation inactivation, Biochim. Biophys. Acta 163: 188 (1968).

    Article  CAS  Google Scholar 

  8. E. S. Kempner and W. Schlegel, Size determination of enzymes by radiation inactivation, Anal. Biochem. 92: 2 (1979).

    CAS  Google Scholar 

  9. W. Schlegel, E. S. Kempner, and M. Rodbell, Activation of adenylate cyclase in hepatic membranes involves interactions of the catalytic unit with multimeric complexes of regulatory proteins, J. Biol. Chem. 254: 5168 (1979).

    CAS  Google Scholar 

  10. E. S. Kempner and H. T. Haigler, The influence of low temperature on the radiation sensitivity of enzymes, J. Biol. Chem., in press (1983).

    Google Scholar 

  11. E. S. Kempner, J. H. Miller, W. Schlegel, and J. Z. Hearon, The functional unit of polyenzymes. Determination by radiation inactivation, J. Biol.. Chem. 255: 6826 (1980).

    PubMed  CAS  Google Scholar 

  12. M. E. Lowe and E. S. Kempner, Radiation inactivation of the glycoprotein, invertase, J. Biol. Chem., in press (1982).

    Google Scholar 

  13. D. Parkinson and B. A. Callingham, Irradiation inactivation analysis of acetylcholinesterase and the effect of buffer salts, Rad. Res. 90: 252 (1982).

    CAS  Google Scholar 

  14. R. L. Kincaid, E. Kempner, V. C. Manganiello, J. C. Osborne Jr.,and M. Vaughan, Calmodulin-activated cyclic nucleotide phosphodiesterase from brain. Relationship of subunit structure to activity assessed by radiation inactivation, J. Biol. Chem. 256 (21): 11351 (1981).

    PubMed  CAS  Google Scholar 

  15. P. Simon, S. Swillens, and J. E. Dumont, Size determination of an equilibrium enzymic system by radiation inactivation, theoretical considerations, Biochem. J. 205: 477 (1982).

    PubMed  CAS  Google Scholar 

  16. M. P. Czech, J. Massague, and P. F. Pilch, The insulin receptor: structural features, TIBS 68: 222 (1981).

    Google Scholar 

  17. J. T. Harmon, C. R. Kahn, E. S. Kempner, and W. Schlegel, Characterization of the insulin receptor in its membrane environment by radiation inactivation, J. Biol. Chem. 255: 3412 (1980)

    PubMed  CAS  Google Scholar 

  18. J. T. Harmon, E. S. Kempner, and C. R. Kahn, Demonstration by radiation inactivation that insulin alters the structure of the insulin receptor in rat liver membranes, J. Biol. Chem. 256: 7719 (1981).

    PubMed  CAS  Google Scholar 

  19. R. J. Pollet, E. S. Kempner, M. L. Standaert, and B. A. Haase, Structure of the insulin receptor of the cultured human lymphoblastoid cell IM-9, evidence suggesting that two subunits are required for insulin binding, J. Biol. Chem. 257: 894 (1982).

    CAS  Google Scholar 

  20. J. T. Harmon and J. A. Hedo, Characterization of the chemical and functional nature of a membrane regulator of insulin receptor affinity, 63rd meeting endocrine society (Cincinatti), abstract No 259: 147 (1981).

    Google Scholar 

  21. R. E. Corin and D. B. Donner, Insulin receptors convert to a higher affinity state subsequent to hormone binding, a two-state model for the insulin receptor, J. Biol. Chem. 257: 104 (1982).

    PubMed  CAS  Google Scholar 

  22. D. B. Donner and R.E. Corin, Formation of a receptor state from which insulin dissociates slowly in hepatic cells and plasma membranes, J. Biol. Chem. 255: 9005 (1980).

    PubMed  CAS  Google Scholar 

  23. R. J. Pellet, M. L. Standaert, and B.A. Haase, Insulin binding to the human lymphocyte receptor, evaluation of the negative cooperativity model, J. Biol. Chem. 252: 5828, (1977).

    Google Scholar 

  24. M. Rodbell, The role of hormone receptors and GTPregulatory proteins in membrane transduction, Nature 284: 17 (1980).

    Article  PubMed  CAS  Google Scholar 

  25. A. M. Spiegel and R. W. Downs, Jr, Guanine nucleotides: key regulators of hormone receptor-adenylate cyclase interaction, Endocrine Reviews 2: 275 (1981).

    Article  PubMed  CAS  Google Scholar 

  26. Th. Pfeuffer, Guanine nucleotide-controlled interactions between components of adenylate cyclase, FEBS Letts 101: 85 (1979).

    Article  CAS  Google Scholar 

  27. S. Strittmatter and E. J. Neer, Properties of the separated catalytic and regulatory units of brain adenylate cyclase, Proc. Natl. Acad. Sci. 77: 6344 (1980).

    Article  PubMed  CAS  Google Scholar 

  28. D. Stengel and J. Hanoune, The catalytic unit of ram sperm adenylate cyclase can be activated through the guanine nucleotide regulatory component and prostaglandin receptors of human erythrocyte, J. Biol. Chem. 256: 5394 (1981).

    PubMed  CAS  Google Scholar 

  29. E. M. Ross, A. C. Howlett, K. M. Ferguson, and A. G. Gilman, Reconstitution of hormone-sensitive adenylate cyclase activity with resolved components of the enzyme, J. Biol. Chem. 253: 6401 (1978).

    PubMed  CAS  Google Scholar 

  30. D. Stengel, L. Guenet, and J. Hanoune, Proteolytic solubilization of adenylate cyclase from membranes deficient in regulatory component, J. Biol. Chem. 257: 10818 (1982).

    PubMed  CAS  Google Scholar 

  31. T. B. Nielsen, P. M. Lad, M. S. Preston, E. Kempner, W. Schlegel, and M. Rodbell, Structure of the turkey erythrocyte adenylate cyclase system, Proc. Natl. Acad. Sci. 78: 722 (1981).

    Article  PubMed  CAS  Google Scholar 

  32. R. B. Martin, J. M. Stein, E. L. Kennedy, C. A. Doberska, and J. C. Metcalfe, Transient complexes, a new structural model for the activation of adenylate cyclase by hormone receptors (guanine nucleotides/irradiation inactivation), Biochem. J. 184: 253 (1979).

    PubMed  CAS  Google Scholar 

  33. W. Schlegel, D. M. F. Cooper, and M. Rodbell, Inhibition and activation of fat cell adenylate cyclase by GTP is mediated by structures of different size, Arch. Biochem. Biophys. 201: 678 (1980).

    Article  CAS  Google Scholar 

  34. G. L. Johnson, V. I. MacAndrew Jr, and P. F. Pilch, Identification of the glucagon receptor in rat liver membranes by photoaffinity crosslinking, Proc. Natl. Acad. Sci. 78: 875 (1981).

    Article  PubMed  CAS  Google Scholar 

  35. D. Atlas and A. Levitzki, Tentative identification of 6-adreno-receptor subunits, Nature 272: 370 (1978).

    Article  PubMed  CAS  Google Scholar 

  36. A. D. Strosberg, G. Vauquelin, 0. Durieu-Trautmann, C. Delavier-Klutchko, S. Bottari, and C. André, Towards the chemical and functional characterization of the 5-adrenergic receptor, TIBS 5: 11 (1980).

    CAS  Google Scholar 

  37. T. L. Innerarity, E. S. Kempner, D. Y. Hui, and R. W. Mahley, Functional unit of the low density lipoprotein receptor of fibroblasts: a 100,000dalton structure with multiple binding sites, Proc. Natl. Acad. Sci. 78: 4378 (1981).

    Article  PubMed  CAS  Google Scholar 

  38. C. J. Steer, E. S. Kempner, and G. Ashwell, Molecular size of the hepatic receptor for asialoglycoproteins determined in situ by radiation inactivation, J. Biol. Chem. 256: 5851 (1981).

    PubMed  CAS  Google Scholar 

  39. C. Fewtrell, E. Kempner, G. Poy, and H. Metzger, Unexpected findings from target analysis of immunoglobulin E and its receptor, Biochemistry 20: 6589 (1981).

    Article  PubMed  CAS  Google Scholar 

  40. A. Doble and L. L. Iversen, Molecular size of benzodiazepine receptor in rat brain in situ: evidence for a functional dimer, Nature 295: 522 (1982).

    Article  PubMed  CAS  Google Scholar 

  41. S. M. Paul, E. S. Kempner,and P. Skolnick, In situ molecular-weight determination of brain and peripheral benzodiazepine binding sites, Eur. J. Pharmacol. 76:465 (1982).

    Google Scholar 

  42. L. R. Chang, E. A. Barnard, M. M. S. Lo, and J. O. Dolly, Molecular sizes of benzodiazepine receptors and the interacting GABA receptors in the membrane are identical, FEBS letts 126: 309 (1981).

    Article  CAS  Google Scholar 

  43. M. M. S. Lo, E. A. Barnard, and J. O. Dolly, Size of acetylcholine receptors in the membrane, an improved version of the radiation inactivation method, Biochemistry 21: 2210 (1982).

    Article  PubMed  CAS  Google Scholar 

  44. S. Uchida, K. Matsumoto, K. Takeyasu, H. Higuchi, and H. Yoshida, Molecular mechanism of the effects of guanine nucleotide and sulfhydryl reagent on muscarinic receptors in smooth muscles studied by radiation inactivation, Life Sci. 31: 201 (1982).

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Fondation pour recherches medicales Dept. of Medicine, University of Geneva, 64, av. de la Roserie, CH-1211, Geneva 4, Switzerland

    Werner Schlegel

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  1. Werner Schlegel
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Editors and Affiliations

  1. Institute of Pharmacology and Pharacognosy, University of Urbino, Urbino, Italy

    F. Cattabeni

  2. Institute of Pharmacology and Pharmacognosy, University of Milan, Milan, Italy

    S. Nicosia

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© 1984 Springer Science+Business Media New York

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Schlegel, W. (1984). Structure-Function Relations for Cell Surface Receptors and Adenylate Cyclase: Studies Using Target Size Analysis of Radiation Inactivation. In: Cattabeni, F., Nicosia, S. (eds) Principles and Methods in Receptor Binding. NATO ASI Series, vol 72. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1577-4_14

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  • DOI: https://doi.org/10.1007/978-1-4757-1577-4_14

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-1579-8

  • Online ISBN: 978-1-4757-1577-4

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