Evidence for the Role of Receptor Immobilization in Desensitization Subsequent to Hormonal Stimulation

  • David A. Jans
Part of the Molecular Biology Intelligence Unit book series (MBIU)


We saw in the previous chapter that a body of indirect and direct experimental evidence supports the notion that receptor lateral mobility plays an integral role at the level of the membrane in transducing the stimulatory signal represented by hormone binding to receptor. This chapter intends to discuss the evidence for the assertion that if receptor lateral movement is important in hormonal stimulation, as it appears to be, arrestation of receptor movement must be central to the abrogation of the stimulatory signal subsequent to hormonal addition, as part of the cellular downregulatory apparatus.1,2 Particularly in the case of GTP-binding protein activating receptors where only mobile receptors appear to participate in signal transduction,1–5 it seems reasonable to suggest that desensitization of response subsequent to hormone addition involves the abrogation of receptor movement as an initial step. The evidence for this will be examined in some detail below, the conclusion being that agonistic stimulation triggers receptor immobilization prior to internalization. Receptor immobilization does not appear to exclusively play a role in downregulation of response subsequent to stimulation, however, but is also central to eliciting the stimulatory signal in several receptor systems, including those of tyrosine kinase receptors (as already mentioned in chapter 4) and receptors mediating cell-cell interaction or cell adhesion to the substratum, and these will be dealt with in chapter 7.


Luteinizing Hormone Stimulatory Signal Renal Epithelial Cell Receptor Internalization Mobile Fraction 
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  1. 1.
    Jans DA. The mobile receptor hypothesis revisited: a mechanistic role for hormone receptor lateral mobility in signal transduction. Biochim Biophys Acta 1992; 1113: 271–276.PubMedGoogle Scholar
  2. 2.
    Jans DA, Pavo I. A mechanistic role for polypeptide hormone receptor lateral mobility in signal transduction. Amino Acids 1995; 9: 93–109.Google Scholar
  3. 3.
    Jans DA, Peters R, Jans P et al. Vasopressin V2-receptor mobile fraction and ligand-dependent adenylate cyclase-activity are directly correlated in LLC-PK, renal epithelial cells. J Cell Biol 1991; 114 (1): 53–60.PubMedGoogle Scholar
  4. 4.
    Jans DA, Peters R, Jans P et al. Ammonium chloride affects receptor number and lateral mobility of the vasopressin V2-type receptor in the plasma membrane of LLC-PK, renal epithelial cells: role of the cytoskeleton. Exper Celi Res 1990; 191: 121–128.Google Scholar
  5. 5.
    Zakharova OM, Rosenkranz AA, Sobolev AS. Modification of fluid lipid and mobile protein fractions of reticulocyte plasma membranes affects agonist-stimulated adenylate cyclase. Application of the percolation theory. Biochim Biophys Acta 1995; 1236: 177–184.PubMedGoogle Scholar
  6. 6.
    Jans DA, Hemmings BA. cAMP metabolism in the porcine epithelial cell line LLC-PK,: the central role of the cAMPdependent protein kinase in cAMP-mediated gene induction. Advances in Second Messenger and Phosphoprotein Res 1988; 21: 109–121.Google Scholar
  7. 7.
    Jans DA, Resink TJ, Hemmings BA. A novel LLC-PK, renal epithelial cell mutant impaired in in vivo_down-regulation of cAMPmediated hormonal response. Arch Biochem Biophys 1991; 285: 377–381.PubMedGoogle Scholar
  8. 8.
    Pearson D, Nigg EA, Nagamine Y et al. Mechanisms of cAMP-mediated gene induction; examination of renal epithelial cell mutants affected in the catalytic subunit of the cAMP-dependent protein kinase. Exper Cell Res 1991; 192: 315–318.Google Scholar
  9. 9.
    Hemmings BA. cAMP-mediated proteolysis of the catalytic subunit of the cAMP-dependent protein kinase. FEBS Lett 1986; 196 (1): 126–130.PubMedGoogle Scholar
  10. 10.
    Jans DA, Gajdas EL, Dierks-Ventling C et al. Long term stimulation of cAMP production in LLC-PK, cells by salmon calcitonin or a photoactivatable analogue of vasopressin. Biochim Biophys Acta 1987; 930: 392–400.PubMedGoogle Scholar
  11. 11.
    Luzius H, Jans DA, Fahrenholz F. Use of a UV-activatable analogue of vasopressin to select mutants of LLC-PK, cells affected in hormonal responsiveness. J Receptor Res 1989; 10: 61–80.Google Scholar
  12. 12.
    Lutz W, Salisbury J, Kumar R. Vasopressin receptor-mediated endocytosis: current view. Am J Physiol 1991; 261: F1 - F13.PubMedGoogle Scholar
  13. 13.
    Goldstein JL, Brown MS, Anderson RGW et al. Receptor-mediated endocytosis: concepts emerging from the LDL receptor system. Annu Rev Cell Biol 1989; 1: 1–139.Google Scholar
  14. 14.
    Carpentier J-L. The cell biology of the insulin receptor. Diabetologia 1989; 32: 627–635.PubMedGoogle Scholar
  15. 15.
    Thibonnier M. Signal transduction of V,-vascular vasopressin receptors. Regulatory Peptides 1992; 38: 1–11.PubMedGoogle Scholar
  16. 16.
    De Diego JG, Gorden P, Carpentier J-L. The relationship of ligand receptor mobility to internalization of polypeptide hormones and growth factors. Endocrinol 1991; 128 (4): 2136–2140.Google Scholar
  17. 17.
    Fan JY, Carpentier J-L, Gorden P et al. Receptor-mediated endocytosis of insulin: role of microvilli, coated pits and coated vesicles. Proc Natl Acad Sci USA 1982; 79: 7788–7791.PubMedGoogle Scholar
  18. 18.
    Haga T, Haga K, Kameyama K et al. Phosphorylation of muscarinic receptors: regulation by G proteins. Life Sci 1993; 52 (5–6): 421–428.PubMedGoogle Scholar
  19. 19.
    Inglese J, Koch WJ, Caron MG. Isoprenylation in regulation of signal transduction by G-protein-coupled receptor kinases. Nature 1992; 359 (6391): 147–150.PubMedGoogle Scholar
  20. 20.
    Hausdorff WP, Caron MG, Lefkowitz RJ. Turning off the signal: desensitisation of the 3-adrenergic receptor function. FASEB J 1990; 4: 2881–2889.PubMedGoogle Scholar
  21. 21.
    Hosey MM. Diversity of structure, signaling and regulation within the family of muscarinic cholinergic receptors. FASEB J 1992; 6 (3): 845–852.PubMedGoogle Scholar
  22. 22.
    Kim CM, Dion SB, Benovic JL. Mechanism of beta-adrenergic receptor kinase activation by G proteins. J Biol Chem 1993; 268 (21): 15412–15418.PubMedGoogle Scholar
  23. 23.
    Okamoto T, Murayama Y, Hayashi Y et al. Identification of a Gs activator region of the 132-adrenergic receptor that is autoregulated via protein kinase A-dependent phosphorylation. Cell 1991; 67: 723–730.PubMedGoogle Scholar
  24. 24.
    Leberer E, Dignard D, Harcus D et al. The protein kinase homologue Ste20p is required to link the yeast pheromone response G-protein 3y subunits to downstream signalling components. EMBO J 1992; 11 (13): 4815–4824.PubMedGoogle Scholar
  25. 25.
    Haga K, Kameyama K, Haga T et al. Phosphorylation of human ml muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C. J Biol Chem 1996; 271 (5): 2776–2782.PubMedGoogle Scholar
  26. 26.
    Blind E, Bambino T, Nissenson RA. Agonist-stimulated phosphorylation of the G protein-coupled receptor for parathyroid hormone (PTH) and PTH-related protein. Endocrinology 1995; 136 (10): 4271–4277.PubMedGoogle Scholar
  27. 27.
    Maxfield FR, Willingham MC, Haigler HT et al. Binding, surface mobility, internalization, and degradation of rhodamine-labeled a2-macroglobulin. Biochemistry 1981; 20 (18): 5353–5358.PubMedGoogle Scholar
  28. 28.
    Carpentier J-L, Gorden P, Freychat P et al. The fate of [’2 I)iodoepidermal growth factor in isolated hepatocytes: a quantitative electron microscopic autoradiographic study. Endocrinol 1981; 109: 768–775.Google Scholar
  29. 29.
    Jans DA, Jans P, Luzius H et al. Monensin resistant LLC-PK1 mutants are affected in recycling of the adenylate cyclase-stimulating vasopressin V2-receptor. Mol Cell Endocrinol 1991; 81: 165–174.PubMedGoogle Scholar
  30. 30.
    Fishman JB, Dickey BF, Butcher NLR et al. Internalization, recycling, and redistribution of vasopressin receptors in rat hepatocytes. J Biol Chem 1985; 260: 12641–12646.PubMedGoogle Scholar
  31. 31.
    Roettger BF, Rentsch RU, Pinon D et al. Dual pathways of internalization of the cholecystokinin receptor. J Cell Biol 1995; 128 (6): 1029–1041.PubMedGoogle Scholar
  32. 32.
    Schwartz AL, Fridovich SE, Lodish HF. Kinetics of internalization and recycling of the asialoglycoprotein receptor in a hepatoma cell line. J Biol Chem 1982; 257 (8): 4230–4237.PubMedGoogle Scholar
  33. 33.
    Thatte HS, Bridges KR, Golan DE. Microtubule inhibitors differentially affect translational movement, cell surface expression, and endocytosis of transferrin receptors in K562 cells. J Cell Physiol 1994; 160: 345–357.PubMedGoogle Scholar
  34. 34.
    Thatte HS, Bridges KR, Golan DE. ATP depletion causes translational immobilization of cell surface transferrin receptors in K562 cells. J Cell Physiol 1996; 166: 446–452.PubMedGoogle Scholar
  35. 35.
    Fire E, Zwart DE, Roth MG et al. Evidence from lateral mobility studies for dynamic interactions of a mutant influenza hemagglutinin with coated pits. J Cell Biol 1991; 115: 1585–1594.PubMedGoogle Scholar
  36. 36.
    Gilboa L, Ben-Levy R, Yarden Y et al. Roles for a cytoplasmic tyrosine and tyrosine kinase activity in the interactions of Neu receptors with coated pits. J Biol Chem 1995; 270: 7061–7067.PubMedGoogle Scholar
  37. 37.
    Hillman GM, Schlessinger J. Lateral diffusion of epidermal growth factor complexed to its surface receptors does not account for the thermal sensitivity of patch formation and endocytosis. Biochemistry. 1982; 21 (7): 1667–1672.PubMedGoogle Scholar
  38. 38.
    Ullrich A, Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell 1990; 61: 203–212.PubMedGoogle Scholar
  39. 39.
    Jans DA, Peters R, Fahrenholz F. An inverse relationship between receptor internalization and the fraction of laterally mobile receptors for the vasopressin renal-type V2-receptor; an active role for receptor immobilization in down-regulation? FEBS Lett 1990; 274: 223–226.PubMedGoogle Scholar
  40. 40.
    Paccaud JP, Reith W, Johansson B et al. Role of internalization signals and receptor mobility. J Biol Chem 1993; 268 (31): 23191–23196.PubMedGoogle Scholar
  41. 41.
    Levi A, Schechter Y, Neufeld EJ et al. Mobility, clustering and transport of nerve growth factor in embryonal sensory cells and in a sympathetic neuronal cell line. Proc Natl Acad Sci USA 1980; 77: 3469–3473.PubMedGoogle Scholar
  42. 42.
    Schlessinger J, Schechter Y, Willingham MC et al. Direct visualization of binding, aggregation, and internalization of insulin and epidermal growth factor on living fibroblastic cells. Proc Natl Acad Sci USA 1978; 75: 2659–2663.PubMedGoogle Scholar
  43. 43.
    Zidovetzki R, Yarden Y, Schlessinger, J et al. Rotational diffusion of epidermal growth factor complexed to its surface receptor the rapid microaggregation and endocytosis of occupied receptors. Proc Natl Acad Sci USA 1981; 78: 6981–6985.PubMedGoogle Scholar
  44. 44.
    Jans DA, Peters R, Fahrenholz F. Lateral mobility of the phospholipase-C-activating vasopressin V,-type receptor in A7r5 smooth muscle cells: a comparison with the adenylate cyclase-coupled V2-receptor. EMBO J 1990; 9 (9): 2693–2699.PubMedGoogle Scholar
  45. 45.
    Jans DA, Peters R, Zsigo J et al. The adenylate cyclase-coupled vasopressin V2-receptor is highly laterally mobile in membranes of LLC-PK, renal epithelial cells at physiological temperature. EMBO J 1989; 8 (9): 2431–2438.Google Scholar
  46. 46.
    Henis YI, Katzir Z, Shia MA et al. Oligomeric structure of the human asialoglycoprotein receptor: nature and stoichiometry of mutual complexes containing HI and H2 polypeptides assessed by fluorescence photobleaching recovery. J Cell Biol 1990; 111: 1409–1418.PubMedGoogle Scholar
  47. 47.
    Roettger BF, Rentsch RU, Hadac EM et al. Insulation of a G protein-coupled receptor on the plasmalemmal surface of the pancreatic acinar cell. J Cell Biol 1995; 130: 579–590.PubMedGoogle Scholar
  48. 48.
    Carraway III KL, Koland JG, Cerione RA. Visualization of epidermal growth factor (EGF) receptor aggregation in plasma membranes by fluorescence energy transfer. J Biol Chem 1989; 264: 8699–8707.PubMedGoogle Scholar
  49. 49.
    King AC, Cuatrecasas P. Peptide hormone-induced receptor mobility, aggregation and internalization. N Engl J Med 1981; 305: 77–88.PubMedGoogle Scholar
  50. 50.
    Maxfield R, Schlessinger J, Shechter Y et al. Collection of insulin, EGF and a,macroglobulin in the same patches on the surface of cultured fibroblasts and common internalization. Cell 1978; 14 (4): 805–810.PubMedGoogle Scholar
  51. 51.
    Luborsky L, Slater W, Behrman H. Luteinizing hormone (LH) receptor aggregation: modification of ferritin-LH binding and aggregation by prostaglandin Fla and ferritin-LH. Endocrinol 1984; 115: 2217–2226.Google Scholar
  52. 52.
    Mao SY, Varin-Blank N, Edidin M et al. Immobilization and internalization of mutated IgE receptors in transfected cells. J immunol 1991; 146 (3): 958–966.PubMedGoogle Scholar
  53. 53.
    Srinivasan Y, Guzikowski AP, Haugland RP et al. Distribution and lateral mobility of glycine receptors on cultured spinal cord neurons. J Neurosci 1990; 10 (3): 985–995.PubMedGoogle Scholar
  54. 54.
    Velazquez JL, Thompson CL, Barnes EM Jr et al. Distribution and lateral mobility of GABA/benzodiazepine receptors on nerve cells. J Neurosci 1989; 9 (6): 2163–2169.PubMedGoogle Scholar
  55. 55.
    Schlessinger J, Schechter Y, Cuatrecasas P et al. Quantitative determination of the lateral diffusion coefficients of the hormone-receptor complexes of insulin and epidermal growth factor on the plasma membrane of cultured fibroblasts. Proc Natl Acad Sci USA 1978; 75: 5353–5357.PubMedGoogle Scholar
  56. 56.
    Maxfield FR, Willingham MC, Pastan I et al. Binding and mobility of the cell surface receptors for 3,3’,5-triiodo-Lthyronine. Science 1981; 211: 63–65.PubMedGoogle Scholar
  57. 57.
    Gorospe WC, Conn PM. Membrane fluidity regulates development of gonadotrope desensitization to GnRH. Mol Cell Endocrinol 1987; 53 (1–2): 131–140.PubMedGoogle Scholar
  58. 58.
    Yamada K, Carpentier JL, Cheatham B et al. Role of the transmembrane domain and flanking amino acids in internalization and down-regulation of the insulin receptor. J Biol Chem 1995; 270 (7): 3115–3122.PubMedGoogle Scholar
  59. 59.
    Goncalves E, Yamada K, Thatte HS et al. Optimizing transmembrane domain helicity accelerates insulin receptor internalization and lateral mobility. Proc Natl Acad Sci USA 1993; 90: 5762–5766.PubMedGoogle Scholar
  60. 60.
    McClain DA, Maegawa H, Lee J et al. A mutant insulin receptor with defective tyrosine kinase displays no biologic activity and does not undergo endocytosis. J Biol Chem 1987; 262: 14663–14671.PubMedGoogle Scholar
  61. 61.
    Livneh E, Benveniste M, Prywes R et al. Large deletions in the cytoplasmic kinase domain of the epidermal growth factor receptor do not affect its lateral mobility. J Cell Biol 1986; 103: 327–331.PubMedGoogle Scholar
  62. 62.
    Segaloff DL, Puett D, Ascoli M. The dynamics of the steroidogenic response of perfused Leydig tumor cells to human chorionic gonadotropin, ovine luteinizing hormone, cholera toxin, and adenosine 3’,5’-cyclic monophosphate. Endocrinology 1981; 108 (2): 632–638.PubMedGoogle Scholar
  63. 63.
    Bourdage RJ, Fitz TA, Niswender GD. Differential steroidogenic responses of ovine luteal cells to ovine luteinizing hormone and human chorionic gonadotropin. Proc Soc Exp Biol Med 1984; 175 (4): 483–486.PubMedGoogle Scholar
  64. 64.
    Mock EJ, Niswender GD. Internalization of ovine luteinizing hormone/human chorionic gonadotropin recombinants: differential effects of the alpha-and beta-subunits. Endocrinology 1983; 113 (1): 265–269.PubMedGoogle Scholar
  65. 65.
    Mock EJ, Niswender GD. Differences in the rates of internalization of ‘251-labeled human chorionic gonadotropin, luteinizing hormone, and epidermal growth factor by ovine luteal cells. Endocrinology 1983; 113 (1): 259–264.PubMedGoogle Scholar
  66. 66.
    Niswender GD, Roess DA, Sawyer HR et al. Differences in the lateral mobility of receptors for luteinizing hormone (LH) in the luteal plasma membrane when occupied by ovine LH versus human chorionic gonadotropin. Endocrinol 1985; 116: 164–169.Google Scholar
  67. 67.
    Roess DA, Niswender GD, Barisas BG. Cytocholasins and colchicine increase the lateral mobility of human chorionic gonadotropin-occupied luteinizing hormone receptors on ovine luteal cells. Endocrinol 1988; 122: 261–269.Google Scholar
  68. 68.
    Roess DA, Rahman NA, Kenny N. Molecular dynamics of luteinizing hormone receptors on rat luteal cells. Biochim Biophys Acta 1992; 1137: 309–316.PubMedGoogle Scholar
  69. 69.
    Philpott CJ, Rahman NA, Kenny N et al. Rotational dynamics of luteinizing hormone receptors and MHC class I antigens on murine Leydig cells. Biochim Biophys Acta 1995; 1235 (1): 62–68.PubMedGoogle Scholar
  70. 70.
    Prossnitz ER, Kim CM, Benovic JL et al. Phosphorylation of the N-formyl peptide receptor carboxyl terminus by the G protein-coupled receptor kinase, GRK2. J Biol Chem 1995; 270 (3): 1130–1137.PubMedGoogle Scholar
  71. 71.
    Pei G, Kieffer BL, Lefkowitz RJ et al. Agonist-dependent phosphorylation of the mouse delta-opioid receptor: involvement of G protein-coupled receptor kinases but not protein kinase C. Mol Pharmacol 1995; 48 (2): 173–177.PubMedGoogle Scholar
  72. 72.
    Eason MG, Moreira SP, Liggett-SB. Four consecutive serines in the third intracellular loop are the sites for ß-adrenergic receptor kinase-mediated phosphorylation and desensitization of the a2A-adrenergie receptor. J Biol Chem 1995; 270 (9): 4681–4688.PubMedGoogle Scholar
  73. 73.
    Heurich RO, Buggy JJ, Vandenberg MT et al. Glucagon induces a rapid and sustained phosphorylation of the human glucagon receptor in Chinese hamster ovary cells. Biochem Biophys Res Commun 1996; 220 (3): 905–910.PubMedGoogle Scholar
  74. 74.
    Pals-Rylaarsdam R, Xu Y, Witt-Enderby P et al. Desensitization and internalization of the m2 muscarinic acetylcholine receptor are directed by independent mechanisms. J Biol Chem 1995; 270 (48): 29004–29011.PubMedGoogle Scholar
  75. 75.
    Ozcelebi F, Holtmann MH, Rentsch RU et al. Agonist-stimulated phosphorylation of the carboxyl-terminal tail of the se-cretin receptor. Mol Pharmacol 1995; 48 (5): 818–824.PubMedGoogle Scholar
  76. 76.
    Sohlemann-P, Hekman-M, Puzicha-M et al. Binding of purified recombinant 13- arrestin to guanine-nucleotide-bindingprotein-coupled receptors. Eur J Biochem 1995; 232 (2): 464–472.Google Scholar
  77. 77.
    Ozcelebi F, Miller LJ. Phosphopeptide mapping of cholecystokinin receptors on agonist-stimulated native pancreatic acinar cells. J Biol Chem 1995; 270 (7): 3435–3441.PubMedGoogle Scholar
  78. 78.
    Lohse MJ, Andexinger S, Pitcher J et al. Receptor-specific desensitization with purified proteins. Kinase dependence and receptor specificity of 13-arrestin and arrestin in the 32-adrenergic receptor and rhodopsin systems. J Biol Chem 1992; 267 (12): 8558–8564.PubMedGoogle Scholar
  79. 79.
    Garcia-Higuera I, Mayor F Jr. Rapid agonist-induced ß-adrenergic receptor kinase translocation in C6 glioma cells. FEBS Lett 1992; 302 (1): 61–64.PubMedGoogle Scholar
  80. 80.
    Klueppelberg UG, Gates LK, Gorelick FS et al. Agonist regulated phosphorylation of the pancreatic cholecystokinin receptor. J Biol Chem 1991; 266: 2403–2408.PubMedGoogle Scholar
  81. 81.
    Lutz MP, Pinon DI, Gates LK et al. Control of cholecystokinin receptor dephosphorylation in pancreatic acinar cells. J Biol Chem 1993; 268: 12136–12142.PubMedGoogle Scholar
  82. 82.
    Jans DA, Hemmings BA. CAMP-dependent protein kinase activation affects vasopressin V2-receptor number and internalization in LLC-PK, renal epithelial cells. FEBS Lett 1991; 281: 267–271.PubMedGoogle Scholar
  83. 83.
    Johnson GL, Dhanasekaran N. The G-protein family and their interactions with receptors. Endocrine Reviews 1992; 10 (3): 317–331.Google Scholar
  84. 84.
    Sibley DR, Strasser RH, Caron MG et al. Regulation of transmembrane signaling by receptor phosphorylation. Cell 1986; 48: 913–922.Google Scholar
  85. 85.
    Benovic JC, Kuhn H, Weyand I et al. Functional desensitization of the isolated ß-adrenergic receptor by the ß-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48kDa protein). Proc Natl Acad Sci USA 1987; 84: 8879–8882.PubMedGoogle Scholar
  86. 86.
    Meier T, Perez GM, Wallace BG. Immobilization of nicotinic acetylcholine receptors on mouse C2 myotubes by agrininduced protein tyrosine phosphorylation. J Cell Biol 1995; 131 (2): 441–451.PubMedGoogle Scholar
  87. 87.
    Smith PR, Stoner JC, Viggiano SC et al. Effects of vasopressin and aldosterone on the lateral mobility of epithelial Na’ channels in A6 epithelial cells. J Memb Biol 1995; 147 (2): 195–205.Google Scholar
  88. 88.
    Griffin FM Jr, Mullinax PJ. Effects of differentiation in vivo and of lymphokine treatment in vitro on the mobility of C3 receptors of human and mouse mononuclear phagocytes. J Immunol 1985; 135 (5): 3394–3397.PubMedGoogle Scholar
  89. 89.
    Wilden U, Hall SW, Kuhn H. 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 Sci USA 1986; 83: 1174–1178.PubMedGoogle Scholar
  90. 90.
    Bennett N, Sitaramayya A. Inactivation of photoexcited rhodopsin in retinal rods: the roles of rhodopsin kinase and 48-kDa protein (arrestin). Biochemistry 1988; 27: 1710–1715.PubMedGoogle Scholar
  91. 91.
    Sterne-Marr R, Gurevich VV, Goldsmith P et al. Polypeptide variants of ß-arrestin and arrestin 3. J Biol Chem 1993; 268 (21): 15640–15648.PubMedGoogle Scholar
  92. 92.
    Freedman NJ, Liggett SB, Drachman DE et al. Phosphorylation and desensitization of the human 131-adrenergic receptor. Involvement of G protein-coupled receptor kinases and cAMP-dependent protein kinase. J Biol Chem 1995; 270 (30): 17953–17961.PubMedGoogle Scholar
  93. 93.
    Dawson TM, Arriza JL, Jaworsky DE et al. 3-adrenergic receptor kinase-2 and 13- arrestin-2 as mediators of odorant-induced desensitization. Science 1993; 259 (5096): 825–829.PubMedGoogle Scholar
  94. 94.
    Hekman M, Bauer PH, Sohlemann P et al. Phosducin inhibits receptor phosphorylation by the ß-adrenergic receptor kinase in a PKA-regulated manner. FEBS Lett 1994; 343 (2): 120–124.PubMedGoogle Scholar
  95. 95.
    Pitcher JA, Payne ES, Csortos C et al. The G-protein-coupled receptor phosphatase: a protein phosphatase type 2A with a distinct subcellular distribution and substrate specificity. Proc Natl Acad Sci USA 1995; 92 (18): 8343–8347.PubMedGoogle Scholar
  96. 96.
    Kelleher DJ, Pessin JE, Ruoho AE et al. Phorbol ester induces desensitization of adenylate cyclase and phosphorylation of the 3-adrenergic receptor in turkey erythrocytes. Proc Natl Acad Sci USA 1984; 81: 4316–4320.PubMedGoogle Scholar
  97. 97.
    Kwatra MM, Hosey MM. Phosphorylation of the cardiac muscarinic receptor in intact chick neart and its regulation by muscarinic agonist. J Biol Chem 1986; 261: 12429–12432.PubMedGoogle Scholar
  98. 98.
    Kwatra MM, Leung E, Maan AC et al. Correlation of agonist-induced phosphorylation of chick heart muscarinic receptors with receptor desensitization. J Biol Chem 1987; 262: 16314–16321.PubMedGoogle Scholar
  99. 99.
    Robinson MS. The role of clathrin, adaptors and dynamin in endocytosis. Curr Opin Cell Biol 1994: 6 (4): 538–544.PubMedGoogle Scholar
  100. 100.
    Fischer-von-Mollard G, Stahl B, Li C et al. Rab proteins in regulated exocytosis. Trends Biochem Sci 1994; 19 (4): 164–168.PubMedGoogle Scholar
  101. 101.
    Jesaitis AJ, Bokoch GM, Tolley JO et al. Lateral segregation of neutrophil chemotactic receptors into actin-and fodrinrich plasma membrane microdomains depleted in guanyl nucleotide regulatory proteins. J Cell Biol 1988; 107: 921–928.PubMedGoogle Scholar
  102. 102.
    Jesaitis AJ, Tolley JO, Bokoch GM et al. Regulation of chemoattractant receptor interaction with transducing proteins by organizational control in the plasma membrane of human neutrophils. J Cell Biol 1989; 109: 2783–2790.PubMedGoogle Scholar
  103. 103.
    Jesaitis AJ, Tolley JO, Allen RA. Receptor-cytoskeleton interactions and membrane traffic may regulate chemoattractant-induced superoxide production in human granulocytes. J Biol Chem 1986; 261: 13662–13669.PubMedGoogle Scholar
  104. 104.
    Johansson B, Wymann MP, HolmgrenPeterson K et al. N-formyl peptide receptors in human neutrophils display distinct membrane distribution and lateral mobility when labeled with agonist and antagonist. J Cell Biol 1993; 121: 1281–1289.PubMedGoogle Scholar
  105. 105.
    Pavo I, Jans DA, Peters R et al. A vasopressin antagonist that binds to the V2-receptor of LLC-PK, renal epithelial cells is highly laterally mobile but does not effect ligand-induced receptor immobilization. Biochim Biophys Acta 1994; 1223: 240–246.PubMedGoogle Scholar
  106. 106.
    Schmidt JM, Ohlenschlager O, Ruterjans H et al. Conformation of [8-arginine]vasopressin and V1 antagonists in dimethyl sulfoxide solution derived from two-dimensional NMR spectroscopy and molecular dynamics simulation. Eur J Biochem 1991; 201: 355–371.PubMedGoogle Scholar
  107. 107.
    Lutz W, Londowski JM, Sanders M et al. A vasopresin analog that binds but does not activate V1 or V2 vasopressin receptors is not internalized into cells that express V1 or V2 receptors. J Biol Chem 1992; 267: 1109–1115.PubMedGoogle Scholar
  108. 108.
    Eggena P, Lu M, Buku A. Internalization of fluorescent vasotocin-receptor agonist and antagonist in the toad bladder. Am J Physiol 1990; 259: C462 - C470.PubMedGoogle Scholar
  109. 109.
    Fonseca MI, Button DC, Brown RD. Agonist regulation of a1B-adrenergic receptor subcellular distribution and function. J Biol Chem 1995; 270 (15): 8902–8909.PubMedGoogle Scholar
  110. 110.
    Maggio R, Barbier P, Toso A et al. Sodium nitroprusside induces internalization of muscarinic receptors stably expressed in Chinese hamster ovary cell lines. J Neurochem 1995; 65 (2): 943–946.PubMedGoogle Scholar
  111. 111.
    Hermans E, Octave JN, Maloteaux JM. Receptor mediated internalization of neurotensin in transfected Chinese hamster ovary cells. Biochem Pharmacol 1994; 47 (1): 89–91.PubMedGoogle Scholar
  112. 112.
    Gerard NP, Gerard C. Receptor-dependent internalization of platelet-activating factor. J Immunol 1994; 152 (2): 793–800.PubMedGoogle Scholar
  113. 113.
    Hunyady L, Merelli F, Baukal AJ et al. Agonist-induced endocytosis and signal generation in adrenal glomerulosa cells. A potential mechanism for receptor-operated calcium entry. J Biol Chem 1991; 266 (5): 2783–2788.PubMedGoogle Scholar
  114. 114.
    Mantey S, Frucht H, Coy DH et al. Characterization of bombesin receptors using a novel, potent, radiolabeled antagonist that distinguishes bombesin receptor subtypes. Mol Pharmacol 1993; 43 (5): 762–774.PubMedGoogle Scholar
  115. 115.
    Mantyh PIN, Allen CJ, Ghilardi JR et al. Rapid endocytosis of a G protein-coupled receptor: substance P evoked internalization of its receptor in the rat striatum in vivo. Proc Natl Acad Sci USA 1995; 92 (7): 2622–2626.PubMedGoogle Scholar
  116. 116.
    Widmann C, Dolci W, Thorens B et al. Agonist-induced internalization and recycling of the glucagon-like peptide-1 receptor in transfected fibroblasts and in insulinomas. Biochem J 1995; 310 (1): 203–214.PubMedGoogle Scholar
  117. 117.
    Conklin BR, Bourne HR. Structural elements of Ga subunits that interact with G(3y, receptors, and effectors. Cell 1993; 73: 631–641.PubMedGoogle Scholar
  118. 118.
    Birnbaumer L. G proteins in signal transduction. Annu Rev Pharacol Toxicol 1990; 30: 675–705.Google Scholar
  119. 119.
    Clapham DE, Neer EJ. New roles for G-protein ßy-dimers in transmembrane signalling. Nature 1993; 365: 403–406.PubMedGoogle Scholar

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© R.G. Landes Company 1997

Authors and Affiliations

  • David A. Jans
    • 1
  1. 1.John Curtin School of Medical ResearchAustralian National UniversityCanberraAustralia

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