The Complex Structure and Regulation of Adenylate Cyclase

  • Martin Rodbell
Part of the Developments in Pharmacology book series (DIPH, volume 2)

Abstract

For over twenty years the adenylate cyclase system has been investigated as a model for hormone action. Situated in the plasma membrane, the enzyme is regulated by a large number of hormones, neurotransmitters, and such “local” hormones as prostaglandins and purinergic compounds. Initially considered to be a two-component system consisting of the catalytic unit (C) and the recognition components (R) for the various hormones and hormone-like substances, a large body of evidence has accumulated that these systems are multisubunit systems composed minimally of R, C, and nucleotide regulatory components (N) that are responsible for the regulation of adenylate cyclase activity by guanine nucleotides [1, 2]. The enzyme is also regulated in opposing manner by sets of Rand N units that either stimulate or inhibit the enzyme. A functional stimulatory receptor unit has been designated as RN., whereas the opposing inhibitory receptor unit has been designated as the RNi unit or complex [1]. Systems displaying dual regulation contain, by definition, both types of receptor complexes. In addition, different R units are often linked structurally to both Ns and Ni in the same cell membrane.

Keywords

Adenosine Oligomer Angiotensin Histamine Prostaglandin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Rodbell M: The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature 284: 17–22, 1980.PubMedCrossRefGoogle Scholar
  2. 2.
    Ross EM, Gilman AG: Biochemical properties of hormone-sensitive adenylate cyclase. Annu Rev Biochem 49: 533–564, 1980.PubMedCrossRefGoogle Scholar
  3. 3.
    Birnbaumer L, Pohl SL, Rodbell M: Adenyl cyclase in fat cells: I. Properties and the effects of adrenocorticotropin and fluoride. J Biol Chern 244: 3468–3476, 1969.Google Scholar
  4. 4.
    Londos C, Rodbell M: Multiple inhibitory and activating effects of nucleotides and magnesium on adrenal adenylate cyclase. J Biol Chern 250: 3459–3465, 1975.Google Scholar
  5. 5.
    Londos C, Preston MS: Activation of the hepatic adenylate cyclase system by divalent cations: A reassessment. J Biol Chern 252: 5957–5961, 1977.Google Scholar
  6. 6.
    Londos C, Preston MS: Regulation by glucagon and divalent cations of inhibition of hepatic adenylate cyclase by adenosine. J Biol Chem 252: 5951–5956, 1977.PubMedGoogle Scholar
  7. 7.
    Stadel JM, De Lean A, Lefkowitz RJ: Molecular mechanisms of coupling in hormonereceptor-adenylate cyclase systems. Adv Enzymol 53: 1–43, 1982.PubMedGoogle Scholar
  8. 8.
    Hanski E, Sternweis PC, Northrup JK, Dromerick A W, Gilman AG: The regulatory component of adenylate cyclase: Purification and properties of the turkey erythrocyte protein. J Biol Chem 256: 12911–12919, 1981.PubMedGoogle Scholar
  9. 9.
    Sternweis PC, Northrup JK, Smigel MD, Gilman AG: The regulatory component of adenylate cyclase: Purification and properties. J Biol Chem 256: 11517–11526, 1981.PubMedGoogle Scholar
  10. 10.
    Seamon KB, Daly JW: Activation of adenyl ate cyclase by the diterpene forskolin does not require the guanine nucleotide regulatory protein. J Biol Chem 256: 9799–9801, 1981.PubMedGoogle Scholar
  11. 11.
    Florio V A, Ross EM: Direct inhibition of the catalytic protein of adenylate cyclase at the adenosin P site. Fed Proc (abstr), p. 1407, 1982.Google Scholar
  12. 12.
    Ferguson KM, Northrup JK, Gilman AG: Goat antibodies to the regulatory component of adenylate cyclase. Fed Proc (abstr), p. 1407, 1982.Google Scholar
  13. 13.
    Birnbaumer L, Rodbell M: Adenyl cyclase in fat cells: II. Hormone receptors. J Biol Chem 244: 3477–3482, 1969.PubMedGoogle Scholar
  14. 14.
    Bar HP, Hechter O: Adenyl cyclase and hormone action: III. Calcium requirement for ACTH stimulation of adenylate cyclase. Biochem Biophys Res Commun 35: 681–686, 1969.PubMedCrossRefGoogle Scholar
  15. 15.
    Campbell BJ, Woodward G, Borber V: Calcium-mediated interactions between the antidiuretic hormone and renal plasma membranes. J Biol Chem 247: 6167–6173, 1972.PubMedGoogle Scholar
  16. 16.
    Bradham LS, Cheung WY: Calmodulin-dependent adenylate cyclase, in Cheung WY (ed): Calcium and Cell Function. New York, Academic Press, 1980, pp 109–126.Google Scholar
  17. 17.
    Westcott KR, LaPorte DC, Storm DR: Resolution of adenylate cyclase sensitive and insensitive to Ca2+ and calcium-dependent regulatory protein (CDR) by CDR-sepharose affinity chromatography. Proc Natl Acad Sci USA 76: 204–208, 1979.PubMedCrossRefGoogle Scholar
  18. 18.
    Heideman W, Wierman BM, Storm DR: GTP is not required for calmodulin stimulation of bovine brain adenylate cyclase. Proc Natl Acad Sci USA 79: 1462–1465, 1982.PubMedCrossRefGoogle Scholar
  19. 19.
    Jakobs KH, Aktories K, Schultz G: Inhibition of adenylate cyclase by hormones and neurotransmitters. Adv Cyclic Nucleotide Res 14: 173–187, 1981.PubMedGoogle Scholar
  20. 20.
    Simonds, WF, Koski G, Streaty RA, Hjelmeland LM, Klee W A: Solubilization of active opiate receptors. Proc Natl Acad Sci USA 77: 6423–6427, 1980.CrossRefGoogle Scholar
  21. 21.
    Gavish M, Goodman RR, Snyder SH: Solubilized adenosine receptors in the brain: Regulation by guanine nucleotides. Science 215: 1633–1634, 1982.PubMedCrossRefGoogle Scholar
  22. 22.
    Evain D, Anderson WB: Inhibitory effect of guanyl nucleotides toward adenylate cyclase of Chinese hamster ovary cell membranes activated in vitro by cholera toxin. J Biol Chem 254: 8726–8729, 1979.PubMedGoogle Scholar
  23. 23.
    Rodbell M, Lad PM, Nielsen TB, Cooper DMF, Schlegel W, Preston MS, Londos C, Kempner ES: The structure of adenylate cyclase systems. Adv Cyclic Nucleotide Res 14: 3–14, 1981.PubMedGoogle Scholar
  24. 24.
    Jakobs KH, Lasch P, Minuth M, Aktories K, Schultz G: Uncoupling of alpha-adrenoceptormediated inhibition of human platelet adenylate cyclase by N-ethylmaleimide. J Biol Chem 257: 2829–2833, 1982.PubMedGoogle Scholar
  25. 25.
    Wastek GJ, Yamamura HI: Acetylcholine receptors, in Yamamura HI, Enna SJ (eds), Neurotransmitter Receptors, part 2. London, Chapman and Hall, 1981, pp 103–128.Google Scholar
  26. 26.
    Johnson GL, MacAndrew VI, Pilch PF: Identification of the glucagon receptor in rat liver membranes by photo affinity crosslinking. Proc Natl Acad Sci USA 78: 875–878, 1981.PubMedCrossRefGoogle Scholar
  27. 27.
    Lad PM, Welton AF, Rodbell M: Evidence for distinct guanine nucleotide sites in the regulation of the glucagon receptor and of adenyl ate cyclase activity. J Biol Chem 252: 5942–5946, 1977.PubMedGoogle Scholar
  28. 28.
    Schlegel W, Kempner ES, Rodbell M: Activation of adenylate cyclase in hepatic membranes involves interactions of the catalytic unit with multimeric complexes of regulatory proteins. J Biol Chem 254: 5168–5176, 1979.PubMedGoogle Scholar
  29. 29.
    Rodbell M: On the mechanism of activation of fat cell adenylate cyclase by guanine nucleotides: An explanation for biphasic inhibitory and stimulatory effects of the nucleotides and the role of hormones. J Biol Chem 250: 5826–5834, 1975.PubMedGoogle Scholar
  30. 30.
    Katada T, Amano T, Ui M: Modulation by islet-activating protein of adenylate cyclase activity in C6 Glioma cells. J Biol Chem 257: 3739–3746, 1982.PubMedGoogle Scholar

Copyright information

© Martinus Nijhoff Publishers, The Hague 1983

Authors and Affiliations

  • Martin Rodbell

There are no affiliations available

Personalised recommendations