Lateral Mobility of Polypeptide Hormone Receptors and GTP-Binding Proteins

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


As we saw in the previous chapter, the membrane, and in particular its integral and peripheral membrane protein components, are not organized as simplistically, or at least functionally, as envisaged in the fluid mosaic model. Firstly, there is clearly a domain structure, with many physical restrictions to long range protein lateral movement within the plane of the membrane; that is, diffusion may only occur within limited areas or domains of the membrane. Secondly, many membrane proteins have reduced or essentially no mobility through a variety of specific mechanisms, such as linkage to the cytoskeleton, aggregation, etc. Accordingly, it is crucial to any critical examination of the tenets of the Mobile Receptor Hypothesis to examine the evidence for the actual mobility of plasma membrane integral receptors. This chapter will thus concentrate on lateral mobility measurements for plasma membrane integral receptors for polypeptide hormones (see refs. 1–3) and draw general conclusions with respect to receptor movement in the context of the possible relevance to signal transduction. The succeeding chapter (chapter 5) will then deal specifically with the direct and indirect evidence for a role for polypeptide hormone receptor lateral movement in signal transduction, while chapter 6 will discuss the role of receptor lateral movement in the desensitization of response subsequent to hormonal stimulation. Chapter 7 rounds the picture by concentrating on the specific role of receptor immobilization in signaling events relating particularly to immune responses and cell adhesion.


Epidermal Growth Factor Receptor Nerve Growth Factor Insulin Receptor Mobile Fraction Lateral Mobility 
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  1. 1.
    Fahrenholz F, Jans DA, Peters R. Lateral mobility of the V1- and V2-receptors in plasma membranes: a role in signal transduction and receptor down-regulation. Colloques INSERM: Vasopressin 1991; 208: 49–56.Google Scholar
  2. 2.
    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
  3. 3.
    Jans DA, Pavo I. A mechanistic role for polypeptide hormone receptor lateral mobility in signal transduction. Amino Acids 1995; 9: 93–109.Google Scholar
  4. 4.
    Ljungquist P, Wasteson A, Magnusson K-E. Lateral diffusion of plasma membrane receptors labelled with either platelet-derived growth factor (PDGF) or wheat germ agglutinin (WGA) in human leukocytes and fibroblasts. Bioscience Reports 1989; 9: 63–73.PubMedGoogle Scholar
  5. 5.
    Ljungquist-Hoeddelius P, Lirvall M, Wasteson A et al. Lateral diffusion of PDGF-13 receptor in human fibroblasts. Bioscience Reports 1991; 11 (1): 43–52.Google Scholar
  6. 6.
    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
  7. 7.
    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
  8. 8.
    Zidovetzki R, Yarden Y, Schlessinger, J et al. Rotational diffusion of epidermal growth factor complexed to surface receptors reflects rapid microaggregation and endocytosis of occupied receptors. Proc Natl Acad Sci USA 1981; 78: 6981–6985.PubMedGoogle Scholar
  9. 9.
    Hillman GM, Schlessinger J. The 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: 1667–1672.PubMedGoogle Scholar
  10. 10.
    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
  11. 11.
    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
  12. 12.
    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
  13. 13.
    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
  14. 14.
    Jans DA, Peters R, Fahrenholz F. Lateral mobility of the phospholipase-C-activating vasopressin V1-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
  15. 15.
    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-PK1 renal epithelial cells:role of the cytoskeleton. Exper Cell Res 1990; 191: 121–128.Google Scholar
  16. 16.
    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
  17. 17.
    Jans DA, Peters R, Jans P et al. Vasopressin V2-receptor mobile fraction and ligand-dependent adenylate cyclase-activity are directly correlated in LLC-PK1 renal epithelial cells. J Cell Biol 1991; 114 (1): 53–60.PubMedGoogle Scholar
  18. 18.
    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
  19. 19.
    Schlessinger J, Axelrod D, Koppel DE et al. Lateral transport of a lipid probe and labeled proteins on a cell membrane. Science 1977; 195: 307–309.PubMedGoogle Scholar
  20. 20.
    Livneh E, Benveniste M, Prywes R et al. Large deletions in the cytoplasmic kinase domian of the epidermal growth factor receptor do not affect its lateral mobility. J Cell Biol 1986; 103: 327–331.PubMedGoogle Scholar
  21. 21.
    Rees AR, Gregoriou M, Johnson P et al. High affinity epidermal growth factor receptors on the surface of A-431 cells have restricted lateral diffusion. EMBO J 1984; 3: 1843–1847.PubMedGoogle Scholar
  22. 22.
    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
  23. 23.
    Venkatakrishnan G, McKinnon CA, Pilapil CG et al. Nerve growth factor receptors are preaggregated and immobile on responsive cells. Biochemistry 1991; 30 (11): 2748–2753.PubMedGoogle Scholar
  24. 24.
    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
  25. 25.
    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
  26. 26.
    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
  27. 27.
    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
  28. 28.
    Gupte SS. Localization and diffusion of glucagon receptor in rat hepatocytes. Receptor 1994; 4 (3): 175–190.PubMedGoogle Scholar
  29. 29.
    Edidin M, Aszalos A, Damjanovich S et al. Lateral diffusion measurements give evidence for association of the Tac peptide of the IL-2 receptor with the T27 peptide in the plasma membrane of HUT-102-B2 T cells. J Immunol 1988; 141: 1206–1210.PubMedGoogle Scholar
  30. 30.
    Taniguchi T, Minami Y. The IL-2/IL-2 receptor system: a current overview. Cell 1993; 73: 5–8.PubMedGoogle Scholar
  31. 31.
    Jans DA, Resink TJ, Wilson E-L et al. Isolation of a mutant LLC-PK, cell line defective in hormonal responsiveness: a pleiotropic lesion affecting receptor function. Eur J Biochem 1986; 160: 407–412.PubMedGoogle Scholar
  32. 32.
    Jans DA, Resink TJ, Hemmings BA. Complementation between LLC-PK, mutants affected in polypeptide hormone receptor function. Eur J Biochem 1987; 162: 571–576.PubMedGoogle Scholar
  33. 33.
    Luzius H, Jans DA, Jans P et al. Isolation and genetic characterization of a renal epithelial cell mutant defective in vasopressin Vz type receptor binding and function. Exper Cell Res 1991; 195: 478–484.Google Scholar
  34. 34.
    Helmreich EJM, Elson EL. Protein and lipid mobility. Adv in Cyclic Nucleotide and Prot Phosphor Res 1984; 18: 1–62.Google Scholar
  35. 35.
    Schlessinger J. Signal transduction by allosteric receptor oligomerization. Trends Biochem Sci 1988; 13: 443–447.PubMedGoogle Scholar
  36. 36.
    Schlessinger J. The epidermal growth factor receptor as a multifunctional allosteric protein. Biochemistry 1989; 27: 3119–3123.Google Scholar
  37. 37.
    Ullrich A, Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell 1990; 61: 203–212.PubMedGoogle Scholar
  38. 38.
    Yarden Y, Schlessinger J. Epidermal growth factor induces rapid, reversible aggregation of the purified epidermal growth factor receptor. Biochem 1987; 26: 1443–1451.Google Scholar
  39. 39.
    Yarden Y, Schlessinger J. Self-phosphorylation of epidermal growth factor: evidence for a model of intermolecular allosteric activation. Biochem 1987; 26: 1434–1442.Google Scholar
  40. 40.
    Gadella TW Jr, Jovin TM. Oligomerization of epidermal growth factor receptors on A431 cells studied by time-resolved fluorescence imaging microscopy. A stereochemical model for tyrosine kinase receptor activation. J Cell Biol 1995; 129 (6): 1543–1558.PubMedGoogle Scholar
  41. 41.
    Cochet C, Kashles O, Chambaz EM et al. Demonstration of epidermal growth factor-induced receptor dimerization in living cells using a chemical covalent cross-linking agent. J Biol Chem 1988; 263: 3290–3295.PubMedGoogle Scholar
  42. 42.
    Heffetz D, Zick Y. Receptor aggregation is necessary for activation of the soluble insulin receptor kinase. J Biol Chem 1986; 261: 889–894.PubMedGoogle Scholar
  43. 43.
    Johnson JD, Wong H-L, Rutter WJ. Properties of the insulin receptor ectodomain. Proc Natl Acad Sci USA 1988; 85: 7516–7520.PubMedGoogle Scholar
  44. 44.
    Kahn CR, Baird KL, Jarrett DB et al. Direct demonstration that receptor crosslinking or aggregation is important in insulin action. Proc Natl Acad Sci USA 1978; 75 (9): 4209–4213.PubMedGoogle Scholar
  45. 45.
    Sorokin A. Activation of the EGF receptor by insertional mutations in its juxtamembrane regions. Oncogene 1995; 11 (8): 1531–1540.PubMedGoogle Scholar
  46. 46.
    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 (13): 7061–7067.PubMedGoogle Scholar
  47. 47.
    Weiner DB, Lui J, Cohen JA et al. A point mutation in the neu oncogene mimics ligand induction of receptor aggregation. Nature 1989; 339: 230–231.PubMedGoogle Scholar
  48. 48.
    Yamada K, Goncalves E, Carpentier JL et al. Transmembrane domain inversion blocks ER release and insulin receptor signaling. Biochemistry 1995; 34 (3): 946–954.PubMedGoogle Scholar
  49. 49.
    Kraus MH, Popescu NC, Amsbaugh SC et al. Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms. EMBO J 1987; 6 (3): 605–610.PubMedGoogle Scholar
  50. 50.
    Honegger AM, Kris RM, Ullrich A et al. Evidence that autophosphorylation of solubilized EGF-receptors is mediated by intermolecular cross phosphorylation. Proc Natl Acad Sci USA 1989; 86: 925–929.PubMedGoogle Scholar
  51. 51.
    Honegger AM, Schmidt A, Ullrich A et al. Evidence for EGF-induced autophosphorylation of the EGF-receptor in living cells. Mol Cell Biol 1990; 10 (8): 4035–4044.PubMedGoogle Scholar
  52. 52.
    Ballotti R, Lammers R, Scimeca I-C et al. Intermolecular transphosphorylation between insulin receptors and EGF-insulin receptor chimerae. EMBO J 1989; 8: 3303–3309.PubMedGoogle Scholar
  53. 53.
    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
  54. 54.
    Giugni TD, Braslau DL, Haigler HT. Electric field-induced redistribution and postfield relaxation of epidermal growth factor receptors on A431 cells. J Cell Biol 1987; 104 (5): 1291–1297.PubMedGoogle Scholar
  55. 55.
    Heller-Harrison RA, Morin M, Czech MP. Insulin regulation of membrane-associated insulin receptor substrate 1. J Biol Chem 1995; 270 (41): 24442–24450.PubMedGoogle Scholar
  56. 56.
    Noh DY, Shin SH, Rhee SG. Phosphoinositide-specific phospholipase C and mitogenic signaling. Biochim Biophys Acta 1995; 1242 (2): 99–113.PubMedGoogle Scholar
  57. 57.
    Rozakis F, Adcock M, van der Geer P et al. MAP kinase phosphorylation of mSosl promotes dissociation of mSosl-Shc and mSosl-EGF receptor complexes. Oncogene 1995; 11 (7): 1417–1426.Google Scholar
  58. 58.
    Langlois WJ, Sasaoka T, Saltiel AR et al. Negative feedback regulation and desensitization of insulin-and epidermal growth factor-stimulated p2lras activation. J Biol Chem 1995; 270 (43): 25320–25323.PubMedGoogle Scholar
  59. 59.
    Eldar H, Ben-Chaim J, Livneh E. Deletions in the regulatory or kinase domains of protein kinase C-alpha cause association with the cell nucleus. Exper Cell Res 1992; 202: 259–266.Google Scholar
  60. 60.
    Leach KL, Powers EA, Ruff VA et al. Type 3 protein kinase C localization to the nuclear envelope of phorbol ester-treated NIH 3T3 cells. J Cell Biol 1992; 109: 685–695.Google Scholar
  61. 61.
    Leach KL, Ruff VA, Jarpe MB et al. a thrombin stimulates nuclear diglyceride levels and differential nuclear localization of protein kinase C isozymes in IIC9 cells. J Biol Chem 1992; 267: 21816–21822.PubMedGoogle Scholar
  62. 62.
    Chen R-H, Sarnecki C, Blenis J. Nuclear localization and regulation of erk-and rsk-encoded protein kinases. Mol Cell Biol 1992; 12: 915–927.PubMedGoogle Scholar
  63. 63.
    Ettehadieh E, Sanghera JS, Pelech SL et al. Tyrosyl phosphorylation and activation of MAP kinases by p565*. Science 1992; 255: 853–855.PubMedGoogle Scholar
  64. 64.
    Gronowski AM, Rotwein P. Rapid changes in nuclear protein tyrosine phosphorylation after growth hormone treatment in vivo. Identification of phosphorylated mitogenactivated protein kinase and STAT91. J Biol Chem 1994; 269: 7874–7878.PubMedGoogle Scholar
  65. 65.
    Jans DA. Nuclear signaling pathways for polypeptide ligands and their membrane-receptors? FASEB J 1994; 8: 841–847.PubMedGoogle Scholar
  66. 66.
    Jans DA. Regulation of protein transport to the nucleus by phosphorylation. Biochem J 1995; 311: 705–716.PubMedGoogle Scholar
  67. 67.
    Heldin C-H. Structural and functional studies on platelet-derived growth factor. EMBO J 1992; 11: 4251–4259.PubMedGoogle Scholar
  68. 68.
    Panaotou G, Waterfield MD. The assembly of signalling complexes by receptor tyrosine kinases. Bioessays 1993; 15 (3): 171–177.Google Scholar
  69. 69.
    Neubig RR, Sklar LA. Subsecond modulation of formyl peptide-linked guanine nucleotide-binding proteins by guanosine 5’O-(3-thio)triphosphate in permeabilized neutrophils. Mol Pharmacol 1993; 43 (5): 734–740.PubMedGoogle Scholar
  70. 70.
    Brandt DR, Ross EM. Catecholamine-stimulated GTPase cycle; multiple sites of regulation by (3-adrenergic receptor and Mg’ studied in reconstituted receptor-G, vesicles. J Biol Chem 1986; 261: 1656–1664.PubMedGoogle Scholar
  71. 71.
    Orly J, Schramm M. Fatty acids as modulators of membrane functions; catecholamine-activated adenylate cyclase of the turkey erythrocyte. Proc Natl Acad Sci USA 1975; 72: 3433–3437.PubMedGoogle Scholar
  72. 72.
    Ransnas LA, Insel PA. Subunit dissociation is the mechanism for hormonal activation of the Gs protein in native membranes. J Biol Chem 1988; 263 (33): 17239–17242.PubMedGoogle Scholar
  73. 73.
    Alousi AA, Jasper JR, Insel PA et al. Stoichiometry of receptor-Gs-adenylate cyclase interactions. FASEB J 1991; 5: 2300–2303.PubMedGoogle Scholar
  74. 74.
    Conklin BR, Bourne HR. Structural elements of Got subunits that interact with Grly, receptors, and effectors. Cell 1993; 73: 631–641.PubMedGoogle Scholar
  75. 75.
    Bourne HR, Sanders DA, McCormick F. The GTPase superfamily: a conserved switch for diverse cell functions. Nature 1990; 348: 125–132.PubMedGoogle Scholar
  76. 76.
    Bourne HR, Sanders DA, McCormick F. The GTPase superfamily: conserved structure and molecular mechanism. Nature 1991; 349: 117–127.PubMedGoogle Scholar
  77. 77.
    Birnbaumer L. G proteins in signal transduction. Annu Rev Pharmacol Toxicol 1990; 30: 675–705.PubMedGoogle Scholar
  78. 78.
    Freissmuth M, Casey PI, Gilman AG. G proteins control diverse pathways of transmembrane signalling. FASEB J 1989; 3: 2125–2131.PubMedGoogle Scholar
  79. 79.
    Ross EM. Signal sorting and amplification through G protein-coupled receptors. Neuron 1989; 3: 141–152.PubMedGoogle Scholar
  80. 80.
    Lamb TD. Stochastic simulation of activation in the G-protein cascade of photoinduction. Biophys J 1994; 67: 1439–1454.PubMedGoogle Scholar
  81. 81.
    Johnson GL, Dhanasekaran N. The G-protein family and their interactions with receptors. Endocrine Reviews 1992; 10 (3): 317–331.Google Scholar
  82. 82.
    Strader CD, Fong TM, Tota MR et al. Structure and function of G proteincoupled receptors. Ann Rev Biochem 1994; 63: 101–132.PubMedGoogle Scholar
  83. 83.
    Thibonnier M. Signal transduction of V,-vascular vasopressin receptors. Regulatory Peptides 1992; 38: 1–11.PubMedGoogle Scholar
  84. 84.
    Meinkoth JL, Taylor SS, Feramisco JR. Dynamics of the distribution of cyclic AMP-dependent protein kinase in living cells. Proc Nati Acad Sci USA 1990; 87: 9595–9599.Google Scholar
  85. 85.
    Nigg EA, Hilz H, Eppenberger HM et al. Rapid and reversible translocation of the catalytic subunit of cAMP-dependent protein kinase type II from the Golgi complex to the nucleus. EMBO J 1985; 4: 2801–2807.PubMedGoogle Scholar
  86. 86.
    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
  87. 87.
    Gill GN, Lazar CS. Increased phosphotyrosine content and inhibition of proliferation in EGF-treated A431 cells. Nature 1981; 293: 305–307.PubMedGoogle Scholar
  88. 88.
    Gregoriou M, Rees AR. Properties of a monoclonal antibody to epidermal growth factor receptor with implications for the mechanism of action of EGF. EMBO J 1984; 3: 929–937.Google Scholar
  89. 89.
    Barnes DW. Epidermal growth factor inhibits growth of A431 human epidermoid carcinoma in serum-free cell culture. J Cell Biol 1982; 93 (1): 1–4.PubMedGoogle Scholar
  90. 90.
    Henis YI, Hekman M, Elson EL et al. Lateral diffusion of 13-receptors in membranes of cultured liver cells. Proc Natl Acad Sci USA 1982; 79: 2907–2911.PubMedGoogle Scholar
  91. 91.
    De Haen C. The non-stoichiometric floating receptor model for hormone sensitive adenylyl cyclase. J Theor Biol 1976; 58: 383–400.PubMedGoogle Scholar
  92. 92.
    Gerard C, Gerard NP. C5A anaphylatoxin and its seven transmembrane-segment receptor. Annu Rev Immunol 1994; 12: 775–808.PubMedGoogle Scholar
  93. 93.
    Saless R, Remy JJ, Levin JM et al. Towards understanding the glycoprotein hormone receptors. Biochimie 1991; 73 (1): 109–120.Google Scholar
  94. 94.
    Henderson R, Baldwin JM, Ceska TA. Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy. J Mol Biol 1990; 213: 899–929.PubMedGoogle Scholar
  95. 95.
    Hausdorff WP, Caron MG, Lefkowitz RJ. Turning off the signal: desensitisation of the ß-adrenergic receptor function. FASEB J 1990; 4: 2881–2889.PubMedGoogle Scholar
  96. 96.
    Bichet DG. Molecular and cellular biology of vasopressin and oxytocin receptors and action in the kidney. Curr Opin Hephrol Hypertens 1994; 3 (1): 46–53.Google Scholar
  97. 97.
    Unson CG, Cypess AM, Kim HN et al. Characterization of deletion and truncation mutants of the rat glucagon receptor. Seven transmembrane segments are necessary for receptor transport to the plasma membrane and glucagon binding. J Biol Chem 1995; 270: 27720–27727.PubMedGoogle Scholar
  98. 98.
    Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol 1982; 157 (1): 105–132.PubMedGoogle Scholar
  99. 99.
    Taylor JM, Neubig RR. Peptides as probes for G protein signal transduction. Cell Signal 1994; 6 (8): 841–849.PubMedGoogle Scholar
  100. 100.
    Kazlauskas A, Cooper JA. Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins. Cell 1989; 58: 1121–1132.PubMedGoogle Scholar
  101. 101.
    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
  102. 102.
    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
  103. 103.
    Kwon G, Axelrod D, Neubig RR. Lateral mobility of tetramethylrhodamine (TMR) labelled G protein a and ßy subunits in NG108–15 cells. Cellular Signalling 1994; 6 (6): 663–679.PubMedGoogle Scholar
  104. 104.
    Neubig RR. Membrane organization in G-protein mechanisms. FASEB J 1994; 8: 939–946.PubMedGoogle Scholar
  105. 105.
    Graeser D, Neubig RR. Compartmentation of receptors and guanine nucleotide-binding proteins in NG108–15 cells: lack of cross-talk in agonist binding among the alpha 2-adrenergic, muscarinic, and opiate receptors. Mol Pharmacol 1993; 43 (3): 434–443.PubMedGoogle Scholar
  106. 106.
    Neer EJ, Smith TF. G protein heterodimers: new structures propel new questions. Cell 1996; 84: 175–178.PubMedGoogle Scholar
  107. 107.
    Clapham DE, Neer EJ. New roles for G-protein ßy-dimers in transmembrane signalling. Nature 1993; 365: 403–406.PubMedGoogle Scholar
  108. 108.
    Stomski FC, Sun Q, Bagley CJ et al. Human interleukin-3 (IL-3) induces disulfide-linked IL-3 receptor alpha-and beta-chain heterodimerization, which is required for receptor activation but not high-affinity binding. Mol Cell Biol 1996; 16 (6): 3035–3046.PubMedGoogle Scholar
  109. 109.
    Roessler E, Grant A, Ju G et al. Cooperative interactions between the interleukin 2 receptor alpha and beta chains alter the interleukin-2-binding affinity of the receptor subunits. Proc Natl Acad Sci USA 1994; 91 (8): 3344–3347.PubMedGoogle Scholar
  110. 110.
    Taga T, Kishimoto T. Cytokine receptors and signal transduction. FASEB J 1992; 6: 3387–3396.PubMedGoogle Scholar
  111. 111.
    Fung MR, Scearce RM, Hoffman JA et al. A tyrosine-kinase physically associates with the beta-subunit of the human IL-2 receptor. J Immunol 1991; 147 (4): 1253–1260.PubMedGoogle Scholar
  112. 112.
    Sato S, Katagiri T, Takaki S et al. IL-5 receptor-mediated tyrosine phosphorylation of SH2/SH3-containing proteins and activation of Bruton’s tyrosine and Janus 2 kinases. J Exp Med 1994; 180: 2101–2111.PubMedGoogle Scholar
  113. 113.
    Jans DA. Regulation of protein transport to the nucleus by phosphorylation. Biochem J 1995; 311: 705–716.PubMedGoogle Scholar
  114. 114.
    Jans DA, Huebner. Regulation of protein transport to the nucleus–the central role of phosphorylation. Physiol Rev 1996; 76: 651–685.PubMedGoogle Scholar
  115. 115.
    Schindler C, Shuai K, Prezioso VR et al. Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science 1992; 257: 809–813.PubMedGoogle Scholar
  116. 116.
    Shuai K, Schindler C, Prezioso VR et al. Activation of transcription by IFNgamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science 1992; 258: 1808–1812.PubMedGoogle Scholar
  117. 117.
    Shuai K, Ziemiecki A, Wilks AF et al. Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins. Nature 1993; 366: 580–583.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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