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Molecular Neurobiology

, Volume 1, Issue 1–2, pp 121–154 | Cite as

β-Adrenergic receptor-coupled adenylate cyclase

Biochemical mechanisms of regulation
  • David R. Sibley
  • Robert J. Lefkowitz
Article

Abstract

β-Adrenergic receptor-coupled adenylate cyclase is regulated by both amplification and desensitization processes. Desensitization of adenylate cyclase is divided into two major categories.Homologous desensitization is initiated by phosphorylation of the receptors by a β-adrenergic receptor kinase. This reaction serves to functionally uncouple the receptors and trigger their sequestration away from the cell surface. These sequestered receptors can rapidly recycle to the cell surface or, with time, become down regulated, being destroyed within the cell. Dephosphorylation of the receptors is accomplished in the sequestered compartment of the cell, which may functionally regenerate the receptors and allow their return to the cell surface. Inheterologous desensitization, receptor function is also regulated by phosphorylation, but in the absence of receptor sequestration or down regulation. In this case, phosphorylation serves only to functionally uncouple the receptors, that is, to impair their interactions with the guanine nucleotide regulatory protein Ns. Several protein kinases are capable of promoting this phosphorylation, including the cAMP-dependent kinase and protein kinase C. In addition to the receptor phosphorylation, heterologous desensitization is associated with modifications at the level of the nucleotide regulatory protein Ns and perhaps Ni. Adenylate cyclase systems are also subject to amplification that involves a protein kinase C-mediated phosphorylation of the catalytic unit of the enzyme. Phosphorylation of the catalytic unit enhances its catalytic activity and results in amplified stimulation by the regulatory protein Ns. Other receptor/ effector systems exhibit qualitatively similar regulatory phenomena, suggesting that covalent modification (phosphorylation) may represent a general mechanism for regulating receptor function.

Index Entries

β-Adrenergic receptor adenylate cyclase N proteins desensitization amplification phosphorylation 

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References

  1. Attramadal H. Le Gac F., Jahnsen T., and Hansson V. (1984) β-Adrenergic regulation of Sertoli cell adenylyl cyclase: desensitization by homologous hormone.Mol. Cell Endocrinol. 34, 1–6.PubMedCrossRefGoogle Scholar
  2. Balkin M. S. and Sonenberg M. (1981) Hormone-induced homologous and heterologous desensitization in the rat adipocyte.Endocrinology 109, 1176–1183PubMedGoogle Scholar
  3. Barovsky K., Pedone C., and Brooker G. (1983) Forskolin-stimulated cyclic AMP accumulation mediates protein synthesis-dependent refractoriness in C6-2B rat glioma cells.J. Cyclic Nucleotide Protein Phosphor. Res. 9, 181–189.PubMedGoogle Scholar
  4. Bell J. D. and Brunton L. L. (1986) Enhancement of adenylate cyclase activity in S49 lymphoma cells by phorbol esters.J. Biol. Chem. 261, 12036–12042PubMedGoogle Scholar
  5. Bell J. D., Buxton I. L. O., and Brunton L. L. (1985) Enhancement of adenylate cyclase activity in S49 lymphoma cells by phorbol esters.J. Biol. Chem. 260, 2625–2628.PubMedGoogle Scholar
  6. Benovic J. L., Shorr R. G. L., Caron M. G., and Lefkowitz R. J. (1984) The mammalian β2-adrenergic receptor: Purification and characterization.Biochemistry 23, 4510–4518.PubMedCrossRefGoogle Scholar
  7. Benovic J. L., Pike L. J., Cerione R. A., Staniszewski C., Yoshimasa T., Codina J., Caron M. G., and Lefkowitz R. J. (1985) Phosphorylation of the mammalian β-adrenergic receptor by cyclic AMP-dependent protein kinase.J. Biol. Chem. 260, 7094–7101.PubMedGoogle Scholar
  8. Benovic J. L., Strasser R. H., Caron, M. G., and Lefkowitz R. J. (1986a) β-Adrenergic receptor kinase: Identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor.Proc. Natl. Acad. Sci. USA 83, 2797–2801.PubMedCrossRefGoogle Scholar
  9. Benovic J. L., Mayor F., Jr., Somers R. L., Caron M. G., and Lefkowitz R. J. (1986) Light-dependent phosphorylation of rhodopsin by β-adrenergic receptor kinase.Nature 322, 869–872.CrossRefGoogle Scholar
  10. Bobik A. and Little P. J. (1984) Role of cyclic AMP in cardiac β-adrenoceptor desensitization: Studies using prenalterol and inhibitors of phosphodiesterase.J. Cardiovasc. Pharmacol. 6, 795–801.PubMedCrossRefGoogle Scholar
  11. Bouvier M., Leeb-Lundberg L. M. F., Benovic J. L., Caron M. G., and Lefkowitz R. J. (1987) Regulation of adrenergic receptor function by phosphorylation. II: Effects of agonist occupancy on phosphorylation of α1-and β2-adrenergic receptors by protein kinase C and the cyclic AMP-dependent protein kinase.J. Biol. Chem. 262, 3106–3113.PubMedGoogle Scholar
  12. Bownds D., Dawes J., Miller J., and Stahlman M. (1972) Phosphorylation of frog photoreceptor membranes induced by light.Nature 237, 125–127.Google Scholar
  13. Briggs M. M., Stadel J. M., Iyengar R., and Lefkowitz R. J. (1983) Functional modification of the guanine nucleotide regulatory protein after desensitization of turkey erythrocytes by catecholamines.Arch. Biochem. Biophys. 224, 142–151.PubMedCrossRefGoogle Scholar
  14. Cerione R. A., Strulovici B., Benovic J. L., Strader C. D., Caron M. G., and Lefkowitz R. J. (1983) Reconstitution of β-adrenergic receptors in lipid vesicles: Affinity chromatography-purified receptors confer catecholamine responsiveness on a heterologous adenylate cyclase system.Proc. Natl. Acad. Sci. USA 80, 4899–4903.PubMedCrossRefGoogle Scholar
  15. Cerione R. A., Codina J., Benovic J. L., Lefkowitz R. J., Birnbaumer L., and Caron M. G. (1984) The mammalian β2-adrenergic receptor: Reconstitution of functional interactions between pure receptor and pure stimulatory guanine nucleotide binding protein of the adenylate cyclase system.Biochemistry 23, 4519–4525.PubMedCrossRefGoogle Scholar
  16. Chuang D.-M. and Costa E. (1979) Evidence for internalization of the recognition site of β-adrenergic receptors during receptor subsensitivity induced by (-) isoproterenol.Proc. Natl. Acad. Sci. USA 76, 3024–3028.PubMedCrossRefGoogle Scholar
  17. Chuang D.-M., Kinnier W. J., Farber L., and Costa E., (1980) A biochemical study of receptor internalization during β-adrenergic receptor desensitization in frog erythrocytes.Mol. Pharmacol. 18, 348–355.PubMedGoogle Scholar
  18. Clark R. and Butcher R. W. (1979) Desensitization of adenylate cyclase in cultured fibroblasts with prostaglandin E1 and epinephrine.J. Biol. Chem. 254, 9373–9378.PubMedGoogle Scholar
  19. Clark R. B., Friedman J., Prashad N., and Ruoho A. E. (1985) Epinephrine-induced sequestration of the β-adrenergic receptor in cultured S49 WT and cyc lymphoma cells.J. Cyclic Nucleotide Protein Phosphor. Res. 10, 97–119.PubMedGoogle Scholar
  20. Cotecchia S., Leeb-Lundberg L. M. F., Hagen P.-O., Lefkowitz R. J., and Caron M. G. (1985) Phorbol ester effects on α1-adrenergic receptor binding and phosphatidylinositol metabolism in cultured vascular smooth muscle cells.Life Sci. 37, 238–239.CrossRefGoogle Scholar
  21. Cronin M. J. and Canonico P. L. (1985) Tumor promoters enhance basal and growth hormone releasing factor stimulated cyclic AMP levels in anterior pituitary cells.Biochem. Biophys. Res. Commun. 129, 404–410.PubMedCrossRefGoogle Scholar
  22. Cubero A. and Malbon C. C. (1984) The fat cell β-adrenergic receptor.J. Biol. Chem. 259 1344–1350PubMedGoogle Scholar
  23. de Vellis J. and Brooker G. (1974) Reversal of catecholamine refractoriness by inhibitors of RNA and protein synthesis.Science 186, 1221–1223.CrossRefGoogle Scholar
  24. Dixon R. A. F., Kobilka B. K., Strader D. J., Benovic J. L., Dohlman H. G., Frielle T., Bolanowski M. A., Bennett C. D., Rands E., Diehl R. E., Mumford R. A., Slater E. E., Sigal I. S., Caron M. G., Lefkowitz R. J., and Strader C. D. (1986) Cloning of the gene and cDNA for mamalian β-adrenergic, receptor and homology with rhodopsin.Nature (Lond)321, 75–79.CrossRefGoogle Scholar
  25. Dohlman H. G., Caron M. G., and Lefkowitz R. J. (1987) A family of receptors coupled to guanine nucleotide regulatory proteins.Biochemistry 26, 2657–2664.PubMedCrossRefGoogle Scholar
  26. Doss R. C., Perkins J. P., and Harden T. K. (1981) Recovery of β-adrenergic receptors following long-term exposure of astrocytoma cells to catecholamine: Role of protein synthesis.J. Biol. Chem. 256, 12281–12286.PubMedGoogle Scholar
  27. Fishman P. H., Mallorga P., and Talman J. F. (1981) Catecholamine-induced desensitization of adenylate cyclase in rat glioma C6 cells: Evidence for specific uncoupling of beta-adrenergic receptors from a functional regulatory component of adenylate cyclase.Mol. Pharmacol. 20, 310–318.PubMedGoogle Scholar
  28. Fishman P. H., Rebois R. V., and Zaremba T. (1985) Down-regulation of gonadotropin and β-adrenergic receptors by hormones and cyclic AMP.J. Cell. Biochem. 27, 231–239.PubMedCrossRefGoogle Scholar
  29. Frederich R. C., Jr., Waldo G. L., Harden T. K., and Perkins J. P. (1983) Characterization of agonist-induced β-adrenergic receptor-specific desensitization in C62B glioma cells.J. Cyclic Nucleotide Protein Phosphor. Res. 9, 103–118.PubMedGoogle Scholar
  30. Garrity M. J., Andreasen T. J., Storm D. R., and Robertson R. P. (1983) Prostaglandin E-induced heterologous desensitization of hepatic adenylate cyclase: Consequences on the guanyl nucleotide regulatory complex.J. Biol. Chem. 258, 8692–8697.PubMedGoogle Scholar
  31. Gilman A. G. (1984) G proteins and dual control of adenylate cyclase.Cell 36, 577–579.PubMedCrossRefGoogle Scholar
  32. Glass D. B. and Krebs E. G. (1980) Protein phosphorylation catlyzed by cyclic AMP-dependent and cyclic GMP-dependent protein kinases.Ann. Rev. Pharmacol. Toxicol. 20, 363–388.CrossRefGoogle Scholar
  33. Green D. A. and Clark R. B. (1981) Adenylate cyclase coupling proteins are not essential for agonist-specific desensitization of lymphoma cells.J. Biol. Chem. 256, 2105–2108.PubMedGoogle Scholar
  34. Green D. A. and Clark R. B. (1982) Specific muscarinic-cholinergic desensitization in the neuroblastoma-glioma hybrid NG108-15J. Neurochem. 39, 1125–1131.PubMedCrossRefGoogle Scholar
  35. Green D. A., Friedman J., and Richard B. C. (1981) Epinephrine desensitization of adenylate cyclase fromcyc and S49 cultured lymphoma cells.J. Cyclic Nucleotide Res.7, 161–172.PubMedGoogle Scholar
  36. Harden T. K. (1983) Agonist-induced desensitization of the β-adrenergic receptor-linked adenylate cyclase.Pharmacol. Rev. 35, 5–32.PubMedGoogle Scholar
  37. Harden T. K., Cotton C. U., Waldo G. L., Lutton J. K., and Perkins J. P. (1980) Catecholamine-induced alteration in the sedimentation behavior of membrane-bound β-adrenergic receptors.Science 210, 441–443.PubMedCrossRefGoogle Scholar
  38. Harden T. K., Su Y.-F., and Perkins J. P. (1979) Catecholamine-induced desensitization in volves an uncoupling of beta-adrenergic receptors and adenylate cyclase.J. Cyclic Nucleotide Res. 5, 99–106.PubMedGoogle Scholar
  39. Harden T. K., Petch L. A., Traynelis S. F., and Waldo G. L. (1985) Agonist-induced alteration in the membrane form of muscarinic cholinergic receptors.J. Biol. Chem. 260, 13060–13066.PubMedGoogle Scholar
  40. Hargrave P. A., Fong S. L., McDowell J. H., Mas M. T., Curtis D. R., Wang J. K., Juszcak E., and Smith D. P. (1980) The partial primary structure of bovine rhodopsin and its topography in the retinal rod cell disc membrane.Neurochem. Intern. 1, 231–244.CrossRefGoogle Scholar
  41. Hertel C., Muller P., Portenier M., and Staehelin M. (1983a) Determination of the desensitization of β-adrenergic receptors by [3H]CGP-12177.Biochem. J. 216, 669–674.PubMedGoogle Scholar
  42. Hertel C., Staehelin M., and Perkins J. P. (1983b) Evidence for intravesicular \-adrenergic receptors in membrane fractions from desensitized cells: Binding of the hydrophilic ligand CGP-12177 only in the presence of alamethicin.J. Cyclic Nucleotide Protein Phosphor. Res. 9, 119–128.PubMedGoogle Scholar
  43. Hertel C., Portenier M., and Staehelin M. (1986) Evidence for the appearance of an uncoupled form of the \-adrenergic receptor distinct from the internalized receptor.J. Cell. Biochem. 30, 219–225.PubMedCrossRefGoogle Scholar
  44. Hoffman B. B., Mullikin-Kilpatrick D., and Lefkowitz R. J. (1979) Desensitization of beta-adrenergic stimulated adenylate cyclase in turkey erythrocytes.J. Cyclic Nucleotide Res. 5, 355–366.PubMedGoogle Scholar
  45. Hollingsworth E. B., Sears E. B., and Daly J. W. (1985) An activator of protein kinase C (phorbol-12-myristate-13-acetate) augments 2-cholorad-enosine-elicited accumulation of cyclic AMP in guinea pig cerebral cortical particulate preparations.FEBS Lett. 184, 339–341.PubMedCrossRefGoogle Scholar
  46. Hollingsworth E. B., Ukena D., and Daly J. W. (1986) The protein kinase C activator phorbol-12-myristate-13-acetate enhances cyclic AMP accumulation in pheochromocytoma cells.FEBS Lett. 196, 131–134.PubMedCrossRefGoogle Scholar
  47. Homburger V., Lucas M., Cantau B., Barabe J., Penit J., and Bockaert J. (1980) Further evidence that desensitization of \-adrenergic sensitive adenylate cyclase proceeds in two steps: Modification of the coupling and loss of β-adrenergic receptors.J. Biol. Chem. 255, 10436–10444.PubMedGoogle Scholar
  48. Hoyer D., Reynolds E. E., and Molinoff P. G. (1984) Agonist-induced changes in the properties of beta-adrenergic receptors on intact S49 lymphoma cells.Mol. Pharmacol. 25, 209–218.PubMedGoogle Scholar
  49. Hudson T. H. and Johnson G. L. (1981) Functional alterations in components of pigeon erythrocyte adenylate cyclase following desensitization to isoproterenol.Mol. Pharmacol. 20, 694–703.PubMedGoogle Scholar
  50. Hughes R. J. and Insel P. A. (1986) Agonist-mediated regulation of α1- and β2-adrenergic receptor metabolism in a muscle cell line, BC3H-1.Mol. Pharmacol. 29, 521–530.PubMedGoogle Scholar
  51. Insel P. A. and Koachman A. M. (1982) Cytochalasin B enhances hormone and cholera toxin-stimulated cyclic AMP accumulation in S49 lymphoma cells.J. Biol. Chem. 257, 9717–9723.PubMedGoogle Scholar
  52. Insel P. A., Mahan L. C., Motulsky H. J., Stoolman L. M., and Koachman A. M. (1983) Time-dependent decreases in binding affinity of agonists for β-adrenergic receptors of intact S49 lymphoma cells.J. Biol. Chem. 258, 13597–13605.PubMedGoogle Scholar
  53. Iyengar R., Bhat M. K., Riser M. E., and Birnbaumer L. (1981) Receptor-specific desensitization of the S49 lymphoma cell adenylyl cyclase.J. Biol. Chem. 256, 4810–4815.PubMedGoogle Scholar
  54. Jakobs K. H., Bauer S., and Watanabe Y. (1985) Modulation of adenylate cyclase of human platelets by phorbol ester impairment of the hormone-sensitive inhibitory pathway.Eur. J. Biochem. 151, 425–430.PubMedCrossRefGoogle Scholar
  55. Johnson G. L., Wolfe B. B., Harden T. K., Molinoff P. B., and Perkins J. P. (1978) Role of β-adrenergic receptors in catecholamine-induced desensitization of adenyate cyclase in human astrocytoma cells.J. Biol. Chem. 253, 1472–1480.PubMedGoogle Scholar
  56. Johnson J. A., Goka T. J., and Clark R. B. (1986) Phorbol ester-induced augmentation and inhibition of epinephrine-stimulated adenylate cyclase in S49 lymphoma cells.J. Cyclic Nucleotide Res. 151, 199–215.Google Scholar
  57. Kassis S. and Fishman P. H. (1982) Different mechanisms of desensitization of adenylate cyclase by isoproterenol and prostaglandin E1 in human fibroblasts: Role of regulatory components in desensitization.J. Biol. Chem. 257, 5312–5318.PubMedGoogle Scholar
  58. Kassis S. and Fishman P. H. (1984) Functional alteration of the β-adrenergic receptor during desensitization of mammalian adenylate cyclase by β-agonists.Proc. Natl. Acad. Sci. USA 81, 6686–6690.PubMedCrossRefGoogle Scholar
  59. Kassis S. and Sullivan M. (1986) Desensitization of the mammalian β-adrenergic receptor: Analysis of receptor redistribution on nonlinear sucrose gradients.J. Cyclic Nucleotide Res. 11, 35–46.Google Scholar
  60. Kassis S., Olasmaa M., Sullivan M., and Fishman P. H. (1986) Desensitization of the β-adrenergic receptor-coupled adenylate cyclase in cultured mammalian cells.J. Biol. Chem. 261, 12233–12237.PubMedGoogle Scholar
  61. Katada T., Gilman A. G., Watanabe Y., Bauer S., Jakobs K. H. (1985) Protein kinase C phosphorylates the inhibitory guanine nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase.FEBS Lett. 151, 431–437.Google Scholar
  62. Kelleher D. J., Pessin J. E., Ruoho A. E., and Johnson G. L. (1984) Phorbol ester induces desensitization of adenylate cyclase and phosphorylation of the β-adrenergic receptor in turkey erythrocytes.Proc. Natl. Acad. Sci. USA 81, 4316–4320.PubMedCrossRefGoogle Scholar
  63. Kirchik H. J., Iyengar R., and Birnbaumer L. (1983) Human chorionic gonadotropin-induced heterologous desensitization of adenylyl cyclase from highly lutenized rate ovaries: Attenuation of regulatoryN s component activity.Endocrinology 113, 1638–1646.Google Scholar
  64. Kishimoto A., Nishiyama K., Nakanishi H., Uratsuji Nomura H., Takyama Y., and Nishizuka Y. (1985) Studies on the phosphorylation of myelin basic protein by protein kinase C and adenosine 3′:5′-monosphate-dependent protein kinase.J. Biol. Chem. 260, 12492–12499PubMedGoogle Scholar
  65. Koschel K. (1980) A hormone-independent rise of adenosine 3′,5′-monophosphate desensitizes coupling of β-adrenergic receptors by adenylate cyclase in rat glioma C6-cells.Eur. J. Biochem. 108, 163–169.PubMedCrossRefGoogle Scholar
  66. Koshland D. E., Jr., Goldbeter A., Stock J. B. (1982) Amplification and adaptation in regulatory and sensory systems.Science 217, 220–225.PubMedCrossRefGoogle Scholar
  67. Kuhn H., Cook J. H., and Dreyer W. J. (1973) Phosphorylation of rhodopsin in bovine photoreceptor membranes: A dark reaction after illumination.Biochemistry 12, 2495–2502.PubMedCrossRefGoogle Scholar
  68. Kurokawa T., Kurokawa M., and Ishibashi S. (1979) Antimicrotubular agents as inhibitors of desensitization to catecholamine-stimulation of adenylate cyclase in Erhlich ascites tumor cells.Biochem. Biophys. Acta 583, 467–473.PubMedGoogle Scholar
  69. Kwatra M. M. and Hosey M. M. (1986) Phosphorylation of the cardiac muscarinic receptor in intact chick heart and its regulation by a muscarinic agonist.J. Biol. Chem. 261, 12429–12432.PubMedGoogle Scholar
  70. Leeb-Lundberg L. M. F., Cotecchia S., Lomasney J., DeBernardis J. F., Lefkowitz R. J., and Caron M. G. (1985) Phorbol esters promote α1-adrenergic receptor phosphorylation and receptor uncoupling from inositol phospholipid metabolism.Proc. Natl. Acad. Sci. USA 82, 5651–5655.PubMedCrossRefGoogle Scholar
  71. Leeb-Lundberg L. M. F., Cottechia S., DeBlasi A., Caron M. G., and Lefkowitz R. J. (1987) Regulation of adrenergic receptor function by phosphorylation I: Agonist-promoted desensitization and phosphorylation of β1-adrenergic receptors coupled to inositol phospholipid metabolism in DDT1MF-2 smooth muscle cells.J. Biol. Chem. 262, 3098–3105.PubMedGoogle Scholar
  72. Liles W. C., Hunter D. D., Meier K. E., and Nathanson N. M. (1986) Activation of protein kinase C induces rapid internalization and subsequent degradation of muscarinic acetylcholine receptors in neuroblastoma cells.J. Biol. Chem. 261, 5307–5323.PubMedGoogle Scholar
  73. Limas C. J. and Limas C. (1983) Involvement of microtubles in the isoproterenol-induced down-regulation of myocardial β-adrenergic receptors.Biochim. Biophys. Acta 735, 181–184.PubMedCrossRefGoogle Scholar
  74. Limas C. J. and Limas C. (1985) Carbachol induces desensitization of cardiac β-adrenergic receptors through muscarinic M1 receptors.Biochem. Biophys. Res. Commun. 128, 699–704.PubMedCrossRefGoogle Scholar
  75. Mahan L. C., Koachman A. M., and Insel P. A. (1984) Genetic analysis of β-adrenergic receptor internalization and down-regulation.Proc. Natl. Acad. Sci. USA 82, 129–133.CrossRefGoogle Scholar
  76. Mahan L. C., Motolsky H. J., and Insel P. A. (1985) Do agonists promote rapid internalization of β-adrenergic receptors?.Proc. Natl. Acad. Sci. USA 82, 6566–6570.PubMedCrossRefGoogle Scholar
  77. Masters S. B., Quinn M. T., and Brown J. H. (1985) Agonist-induced desensitization of muscarinic receptor-mediated calcium efflux without concomitant desensitization of phosphoinositide hydrolysis.Mol. Pharmacol. 27, 325–332.PubMedGoogle Scholar
  78. Mickey J. C., Tate R., and Lefkowitz R. J. (1975) Subsensitivity of adenylate cyclase and decreased β-adrenergic receptor binding after chronic exposure to (-) isoproterenolin vitro.Mol. Pharmacol. 18, 370–378.Google Scholar
  79. Moylan R. D., Barovsky, K., and Brooker G. (1982) N6, O2-dibutyryl cyclic AMP and cholera toxin-induced β-adrenergic receptor loss in cultured cells.J. Biol. Chem. 257, 4947–4950.PubMedGoogle Scholar
  80. Mukherjee C., Caron M. G., and Lefkowitz R. J. (1975) Catecholamine-induced subsensitivity of adenylate cyclase associated with loss of beta-adrenergic receptor binding sites.Proc. Natl. Acad. Sci. USA 72, 1945–1949.PubMedCrossRefGoogle Scholar
  81. Mukherjee C., Caron M. G., and Lefkowitz R. J. (1976) Regulation of adenylate cyclase coupled β-adrenergic receptors by β-adrenergic catecholamines.Endocrinology 99, 347–357.PubMedGoogle Scholar
  82. Nabika T., Nara Y., Yamori Y., Lovenberg W., and Endo J. (1985) Angiotensin II and phorbol ester enhance isoproterenol- and vasoactive intestinal peptide (VIP)-induced cyclic AMP accumulation in vascular smooth muscle cells.Biochem. Biophys. Res. Commun. 131, 30–36.PubMedGoogle Scholar
  83. Naghshineh S., Noguchi N., Huang K-P., and Londos C. (1986) Activation of adipocyte adenylate cyclase by protein kinase C.J. Biol. Chem. 261, 14534–14538.PubMedGoogle Scholar
  84. Nambi P., Sibley D. R., Stadel J. M., Michel T., Peters J. R., and Lefkowitz R. J. (1984) Cell-free desensitization of catecholamine-sensitive adenylate cyclase.J. Biol. Chem. 259, 4629–4633.PubMedGoogle Scholar
  85. Nambi P., Peters J. R., Sibley D. R., and Lefkowitz R. J. (1985) Desensitization of the turkey erythrocyte β-adrenergic receptor in a cell-free system.J. Biol. Chem. 260, 2165–2171.PubMedGoogle Scholar
  86. Neve K. A. and Molinoff P. B. (1986) Turnover of β1- and β2-adrenergic receptors after down-regulation or irreversible blockade.Mol. Pharmacol. 30, 104–111.PubMedGoogle Scholar
  87. Newcombe D. S., Ciosek C. P., Jr., Ishikawa Y., and Fahey J. V. (1975) Human synoviocytes: Activation and desensitization by prostaglandins and 1-epinephrine.Proc. Natl. Acad. Sci. USA 72, 3124–3128.PubMedCrossRefGoogle Scholar
  88. Nickols G. A. and Brooker G. (1979) Induction of refractoriness to isoproterenol by prior treatment of C6-2B rat astrocytoma cells with cholera toxin.J. Cyclic Nucleotide Res. 5, 435–447.PubMedGoogle Scholar
  89. Nickols G. A. and Brooker G. (1980) Potentiation of cholera toxin-stimulated cyclic AMP production in cultured cells by inhibitors of RNA and protein synthesis.J. Biol. Chem. 255, 23–26.PubMedGoogle Scholar
  90. Nishizuka Y. (1984) The role of protein kinase C in cell surface signal transduction and tumour promotion.Nature 308, 693–698.PubMedCrossRefGoogle Scholar
  91. Noda C., Shinjyo F., Tomomura A., Kato S., Nakamura T., and Ichihara A. (1984) Mechanism of heterologous desensitization of the adenylate cyclase system by glucagon in primary cultures of adult rat hepatocytes.J. Biol. Chem. 259, 7747–7754.PubMedGoogle Scholar
  92. Olianas M. C. and Onali P. (1986) Phorbol esters increase GTP-dependent adenylate cyclase activity in rat brain striatal membranes.J. Neurochem. 47, 890–897.PubMedGoogle Scholar
  93. Orellana S. A., Solski P. A., and Brown J. H. (1985) Phorbol ester inhibits phosphoinositide hydrolysis and calcium mobilization in cultured astrocytoma cells.J. Biol. Chem. 260, 5236–5239.PubMedGoogle Scholar
  94. Pastan I. H. and Willingham M. C. (1981) Receptor-mediated endocytosis of hormones in cultured cells.Ann. Rev. Physiol. 43, 239–250.CrossRefGoogle Scholar
  95. Pfeuffer E., Mollner S., and Pfeuffer T. (1985) Adenylate cyclase from bovine brain cortex: Purification and characterization of the catalytic unit.Embo J. 4, 3675–3679.PubMedGoogle Scholar
  96. Pittman R. N. and Molinoff P. B. (1980) Interactions of agonists and antagonists with β-adrenergic receptors on intact L6 muscle cells.J. Cyclic Nucl. Res. 6, 421–435.Google Scholar
  97. Pittman R. N. and Molinoff P. B. (1983) Interaction of full and partial agonists with beta-adrenergic receptors on intact L6 muscle cells.Mol. Pharmacol. 24, 398–408.PubMedGoogle Scholar
  98. Rich K. A., Codina J., Floyd G., Sekura R., Hildebrandt J. D. and Iyengar R. (1984) Glucagon-induced heterologous desensitization of the MDCK cell adenylyl cyclase.J. Biol. Chem. 259, 7893–7901.PubMedGoogle Scholar
  99. Schramm M. and Selinger Z. (1984) Message transmission: Receptor controlled adenylate cyclase system.Science 225, 1350–1356.PubMedCrossRefGoogle Scholar
  100. Shear M., Insel P. A., Melmon K. L., and Coffino P. (1976) Agonist-specific refractoriness induced by isoproterenol.J. Biol. Chem. 251, 7572–7576.PubMedGoogle Scholar
  101. Shorr R. G. L., Lefkowitz R. J., and Caron M. G. (1981) Purification of the β-adrenergic receptor.J. Biol. Chem. 256, 5820–5826.PubMedGoogle Scholar
  102. Shorr R. G. L., Strohsacker M. W., Lavin T. N., Lefkowitz R. J. and Caron M. G. (1982) The β-adrenergic receptor of the turkey erythrocyte.J. Biol. Chem. 257, 12341–12350.PubMedGoogle Scholar
  103. Sibley D. R., Nambi P., Peters J. R., and Lefkowitz R. J. (1984a) Phorbol diesters promote β-adrenergic receptor phosphorylation and adenylate cyclase desensitization in duck erythrocytes.Biochem. Biophys. Res. Commun. 121, 973–979.PubMedCrossRefGoogle Scholar
  104. Sibley D. R., Peters J. R., Nambi P., Caron M. G., and Lefkowitz R. J. (1984b) Desensitization of turkey erythrocyte adenylate cyclase: β-adrenergic receptor phosphorylation is correlated with attenuation of adenylate cyclase activity.J. Biol. Chem. 259, 9742–9749.PubMedGoogle Scholar
  105. Sibley D. R., Peters J. R., Nambi P., Caron M. G., and Lefkowitz R. J. (1984c) Photoaffinity labeling of turkey erythrocyte beta adrenergic receptors: Degradation of theM r=49,000 protein explains apparent heterogeneity.Biochem. Biophys. Res. Commun. 119, 458–464.PubMedCrossRefGoogle Scholar
  106. Sibley D. R., Strasser R. H., Caron M. G., and Lefkowitz R. J. (1985) Homologous desensitization of adenylate cyclase is associated with phosphorylation of the β-adrenergic receptor.J. Biol. Chem. 260, 3883–3886.PubMedGoogle Scholar
  107. Sibley D. R., Strasser R. H., Benovic J. L., Daniel K., and Lefkowitz R. J. (1986a) Phosphorylation/dephosphorylation of the β-adrenergic receptor regulates its functional coupling to adenylate cyclase and subcellular distribution.Proc. Natl. Acad. Sci. USA 83, 9408–9412.PubMedCrossRefGoogle Scholar
  108. Sibley D. R., Jeffs R. A., Daniel K., Nambi P., and Lefkowitz R. J. (1986b) Phorbol diester treatment promotes enhanced adenylate cyclase activity in frog erythrocytes.Arch. Biochem. Biophys. 244, 373–381.PubMedCrossRefGoogle Scholar
  109. Simantov R., Shjkolnik T., and Sachs L. (1980) Desensitization of enucleated cells to hormones and role of cytoskeleton in control of normal hormonal response.Proc. Natl. Acad. Sci. USA 77, 4798–4802.PubMedCrossRefGoogle Scholar
  110. Simpson I. A. and Pfeuffer T. (1980) Functional desensitization of β-adrenergic receptors of avian erythrocytes by catecholamines and adenosine 3′,5′-phosphate.Eur. J. Biochem. 111, 111–116.PubMedCrossRefGoogle Scholar
  111. Smigel M. D. (1986) Purification of the catalyst of adenylate cyclase.J. Biol. Chem. 261, 1976–1982.PubMedGoogle Scholar
  112. Spiegel A. M. (1987) Signal transduction by guanine nucleotide binding proteins.Mol. Cell. Endocrinol. 49, 1–16.PubMedCrossRefGoogle Scholar
  113. Stadel J. M., De Lean A., Mullikin-kilpatrick D., Sawyer D. D., and Lefkowitz R. J. (1981) Catecholamine-induced desensitization in turkey erythrocytes: cAMP mediated impairment of high affinity agonist binding without alteration in receptor number.J. Cyclic Nucleotide Res. 7, 37–47.PubMedGoogle Scholar
  114. Stadel J. M., De Lean A., and Lefkowitz R. J. (1982a) Molecular mechanisms of coupling in hormone receptor-adenylate cyclase systems.Adv. Enzymol. 53, 1–43.PubMedGoogle Scholar
  115. Stadel J. M., Nambi P., Lavin T. N., Heald S. J., Caron M. G., and Lefkowitz R. J. (1982b) Catecholamine-induced desensitization of turkey erythrocyte adenylate cyclase: Structural alterations in the b-adrenergic receptor revealed by photoaffinity labeling.J. Biol. Chem. 257, 9242–9245.PubMedGoogle Scholar
  116. Stadel J. M., Nambi P., Shorr R. G. L., Sawyer D. F., Caron M. G., and Lefkowitz R. J. (1983a) Catecholamine-induced desensitization of turkey erythrocyte adenylate cyclase is associated with phosphorylation of the β-adrenergic receptor.Proc. Natl. Acad. Sci. USA 80, 3173–3177.PubMedCrossRefGoogle Scholar
  117. Stadel J. M., Strulovici B., Nambi P., Lavin T. N., Briggs M. M., Caron M. G., and Lefkowitz R. J. (1983b) Desensitization of the β-adrenergic receptor of frog erythrocytes: Recovery and characterization of the down-regulated receptors in sequestered vesicles.J. Biol. Chem. 258, 3032–3038.PubMedGoogle Scholar
  118. Staehelin M. and Hertel C. (1983) [3H]CGP-12177, A β-adrenergic ligand suitable for measuring cell surface receptors.J. Rec. Res. 3 (1&2): 35–43.Google Scholar
  119. Staehelin M., Simons P, Jaeggi K., and Wigger N. (1983) CGP-12177: A hydrophilic β-adrenergic receptor radioligand reveals high affinity binding of agonists to intact cells.J. Biol. Chem. 258, 3496–3502.PubMedGoogle Scholar
  120. Strader C. D., Sibley D. R., and Lefkowitz R. J. (1984) Association of sequestered beta-adrenergic receptors with the plasma membrane: A novel mechanism for receptor down regulation.Life Sci. 35, 1601–1610.PubMedCrossRefGoogle Scholar
  121. Strasser R. H., Benovic J. L., Caron M. G., and Lefkowitz R. J. (1986a) β-Agonist- and prostaglandin E1-induced translocation of the β-adrenergic receptor kinase: Evidence that the kinase may act on multiple adenylate cyclase-coupled receptors.Proc. Natl. Acad. Sci. USA 83, 6362–6366.PubMedCrossRefGoogle Scholar
  122. Strasser R. H., Sibley D. R., and Lefkowitz R. J. (1986b) A novel catecholamine-activated adenosine cyclic 3′,5′-phosphate independent pathway for β-adrenergic receptor phosphorylation in wild-type and mutant S49 lymphoma cells: Mechanism of homologous desensitization of adenylate cyclase.Biochemistry 25, 1371–1377.PubMedCrossRefGoogle Scholar
  123. Strulovici B. and Lefkowitz R. J. (1984) Activation, desensitization, and recycling of frog erythrocyte β-adrenergic receptors: Differential perturbation byin situ trypsinization.J. Biol. Chem. 259, 4389–4395.PubMedGoogle Scholar
  124. Strulovici B., Cerione R. A., Kilpatrick B. F., Caron M. G., and Lefkowitz R. J. (1984) Direct demonstration of impaired functionality of a purified desensitized β-adrenergic receptor in a reconstituted system.Science 225, 837–840.PubMedCrossRefGoogle Scholar
  125. Strulovici B., Stadel J. M., and Lefkowitz R. J. (1983) Functional integrity of desensitized β-adrenergic receptors: Internalized receptors reconstitute catecholamine-stimulated adenylate cyclase activity.J. Biol. Chem. 258, 6410–6414.PubMedGoogle Scholar
  126. Stryer L. (1986) Cyclic GMP cascade of vision.Ann. Rev. Neurosci. 9, 87–119.PubMedCrossRefGoogle Scholar
  127. Su Y.-F., Cubeddu L., and Perkins J. P., (1976) Regulation of adenosine 3′, 5′-monophosphate content of human astrocytoma cells: Desensitization to catecholamines and prostaglandins.J. Cyclic Nucleotide Res. 2, 257–270.PubMedGoogle Scholar
  128. Su Y.-F., Harden T. K., and Perkins J. P. (1979) Isoproterenol-induced desensitization of adenylate cyclase in human astrocytoma cells.J. Biol. Chem. 254, 38–41.PubMedGoogle Scholar
  129. Su Y.-F., Harden T. K., and Perkins J. P. (1980) Catecholamine-specific desensitization of adenylate cyclase: Evidence for a multistep process.J. Biol. Chem. 255, 7410–7419.PubMedGoogle Scholar
  130. Sugden D., Vanecek J., Klein D. C., Thomas T. P., and Anderson W. B. (1985) Activation of protein kinase C potentiates isoprenaline-induced cyclic AMP accumulation in rat pinealocytes.Nature 314, 359–361.PubMedCrossRefGoogle Scholar
  131. Sulakhe P. V., Johnson D. D., Phan N. T., and Wilcons R. (1985) Phorbol ester inhibits myoblast fusion and activates β-adrenergic receptor coupled adenylate cyclase.FEBS 186, 281–285.CrossRefGoogle Scholar
  132. Terasaki W. L., Brooker G., de Vellis J., Inglish D., Husu C.-Y., and Moylan R. D. (1978) Involvement of cyclic AMP and protein synthesis in catecholamine refractoriness.Adv. Cyclic Nucleotide Res. 9, 33–52.PubMedGoogle Scholar
  133. Toews M. L. and Perkins J. P. (1984) Agonist-induced changes in β-adrenergic receptors on intact cells.J. Biol. Chem. 259, 2227–2235.PubMedGoogle Scholar
  134. Toews J. L., Harden T. K., and Perkins J. P. (1983) High-affinity binding of agonists to β-adrenergic receptors on intact cells.Proc. Natl. Acad. Sci. USA 80, 3553–3557.PubMedCrossRefGoogle Scholar
  135. Toews M. L., Waldo G. L., Harden T. K., and Perkins J. P. (1984) Relationship between an altered membrane form and a low affinity form of the β-adrenergic receptor occuring during catecholamine-induced desensitization.J. Biol. Chem. 259, 11844–11850.PubMedGoogle Scholar
  136. Toews M. L., Waldo G. L., Harden T. K. and Perkins J. P. (1986) Comparison of binding of125I-Iodopindolol to control and desensitized cells at 37° and on ice.J. Cyclic Nucleotide Res. 11, 47–61.Google Scholar
  137. Waldo G. L., Northup J. K., Perkins J. P., and Harden T. K. (1983) Characterization of an altered membrane form of the β-adrenergic receptor produced during agonist-induced desensitization.J. Biol. Chem. 258, 13900–13908.PubMedGoogle Scholar
  138. Wessels M. R., Mullikin D., and Lefkowitz R. J. (1978) Differences between agonist and antagonist binding following beta-adrenergic receptor desensitization.J. Biol. Chem. 253, 3371–3373.PubMedGoogle Scholar
  139. Wessels M. R., Mullikin D., and Lefkowitz R. J. (1979) Selective alteration in high affinity agonist binding: A mechanism of beta-adrenergic receptor desensitization.Mol. Pharmacol. 16, 10–20.PubMedGoogle Scholar
  140. Wilden U., Hall S. W., and Kuhn H. (1986) Phosphodiesterase activation by photoexcited rhodopsin is quenched when rhodopsin is phosphorylated and binds the intrinsic 48-kDa protein of rod outer segments.Proc. Natl. Acad. USA 83, 1174–1178.CrossRefGoogle Scholar
  141. Yoshimasa T., Sibley D. R., Bouvier M., Lefkowitz R. J., and Caron M. G. (1987) Cross-talk between second messenger generating systems: Phorbol esters induce phosphorylation of the catalytic unit of adenylate cyclase and enhancemenbt of its activity.Nature,327, 67–70.PubMedCrossRefGoogle Scholar
  142. Zaremba T. G. and Fishman P. H. (1984) Desensitization of catecholamine-stimulated adenylate cyclase and down-regulation of beta-adrenergic receptors in rat glioma C6 cells.Mol. Pharmacol. 26, 206–313.PubMedGoogle Scholar
  143. Zick Y., Sagi-Eisenberg R., Pines M., Gierschik P., and Spiegel A. M. (1986) Multisite phosphorylation of the α subunit of transducin by the insulin receptor kinase and protein kinase C.Proc. Natl. Acad. Sci. USA 83, 9294–9297.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1987

Authors and Affiliations

  • David R. Sibley
    • 1
  • Robert J. Lefkowitz
    • 1
  1. 1.Howard Hughes Medical Institute Departments of Medicine and BiochemistryDuke University Medical CenterDurham

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