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Alternative IGF-Related Receptors

  • Chapter
The IGF System

Part of the book series: Contemporary Endocrinology ((COE,volume 17))

Abstract

A substantial number of reports over more than a decade have described variant forms of receptors for insulin-like growth factors (IGFs) and insulin, which differ in structure or ligand specificity from classic type I IGF receptors and insulin receptors as characterized in most mammalian tissues or by expression of their cloned cDNAs. As an introduction to receptor subtypes, we first describe briefly the structure and function of the insulin receptor (IR), type I IGF receptor (IGFR), and insulin-receptor-related receptor (IRR), as reflected in the products of their cloned genes. We then review the properties of known splice variants of these receptors, which represent an obvious potential source of functional heterogeneity. Next, we discuss “atypical” insulin and IGF receptors that apparently bind both insulin and IGFs with high affinity, and attempt to rationalize anomalous observations and assess the structural basis and functional significance of these receptors. Finally we consider the properties of insulin/IGF hybrid receptors, which combine the structures and functions of both receptors and may account for much of the reported heterogeneity in receptor subtypes.

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References

  1. Ullrich A, Bell JR, Chen EY, Herrera R, Petruzzelli LM, Dull TJ, Gray A, Coussens L, Liao YC, Tsubokawa M, Mason A, Seeburg PH, Grunfeld C, Rosen OM, Ramachandran J. Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature 1985; 313: 756–761.

    Article  PubMed  CAS  Google Scholar 

  2. Ebina Y, Ellis L, Jarnagin K, Edery M, Graf L, Clauser E, Ou JH, Masiarz F, Kan YW, Goldfine ID, Roth RA, Rutter WJ. The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling. Cell 1985; 40: 747–758.

    Article  PubMed  CAS  Google Scholar 

  3. Ullrich A, Gray A, Tam AW, Yang Feng T, Tsubokawa M, Collins C, Henzel W, Le Bon T, Kathuria S, Chen E, Jacobs S, Francke U, Ramachandran J, Fujita-Yamaguchi Y. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J 1986; 5: 2503–2512.

    PubMed  CAS  Google Scholar 

  4. Shier P, Watt VM. Primary structure of a putative receptor for a ligand of the insulin family. J Biol Chem 1989; 264: 14605–14608.

    PubMed  CAS  Google Scholar 

  5. Siddle K. The insulin receptor and type I IGF receptor: comparison of structure and function. Prog Growth Factor Res 1992; 4: 301–320.

    Article  PubMed  CAS  Google Scholar 

  6. De Meyts P, Wallach B, Christofferson CT, Urso B, Gronskov K, Latus LJ, Yakushiji F, Ilondo MM, Shymko RM. The insulin-like growth factor-I receptor. Structure, ligand-binding mechanism and signal transduction. Horm Res 1994; 42: 152–169.

    Article  PubMed  Google Scholar 

  7. Cheatham B, Kahn CR. Insulin action and the insulin signaling network. Endocr Rev 1996; 16: 117–142.

    Google Scholar 

  8. Saltiel AR. Diverse signaling pathways in the cellular actions of insulin. Am J Physio11996; 270: E375 — E385.

    Google Scholar 

  9. Ballard FJ, Walton PE, Dunshea FR, Francis GL, Tomas FM. Does IGF-I ever act through the insulin receptor? In Baxter RC, Gluckman PD, Rosenfeld RG, eds. The Insulin-Like Growth Factors and Their Regulatory Proteins. Elsevier, Amsterdam, 1994, pp. 131–138.

    Google Scholar 

  10. Wedekind F, Baer-Pontzen K, Bala-Mohan S, Choli D, Zahn H, Brandenburg D. Hormone binding site of the insulin receptor: analysis using photoaffinity-mediated avidin complexing. Biol Chem Hoppe Seyler 1989; 370: 251–258.

    Article  PubMed  CAS  Google Scholar 

  11. Yip CC, Grunfeld C, Goldfine ID. Identification and characterization of the ligand-binding domain of insulin receptor by use of an anti-peptide antiserum against amino acid sequence 241–251 of the a subunit. Biochemistry 1991; 30: 695–701.

    Article  PubMed  CAS  Google Scholar 

  12. Fabry M, Schaefer E, Ellis L, Kojro E, Fahrenholz F, Brandenburg D. Detection of a new hormone contact site within the insulin receptor ectodomain by the use of a novel photoreactive insulin. J Biol Chem 1992; 267: 8950–8956.

    PubMed  CAS  Google Scholar 

  13. Zhang B, Roth RA. Binding properties of chimeric insulin receptors containing the cysteine-rich domain of either the insulin-like growth factor I receptor or the insulin receptor related receptor. Biochemistry 1991; 30: 5113–5117.

    Article  PubMed  CAS  Google Scholar 

  14. Schumacher R, Mosthaf L, Schlessinger J, Brandenburg D, Ullrich A. Insulin and insulin-like growth factor-1 binding specificity is determined by distinct regions of their cognate receptors. J Biol Chem 1991; 266: 19288–19295.

    PubMed  CAS  Google Scholar 

  15. Andersen AS, Kjeldsen T, Wiberg FC, Vissing H, Schaffer L, Rasmussen JS, De Meyts P, Moller NP. Identification of determinants that confer ligand specificity on the insulin receptor. J Biol Chem 1992; 267: 13681–13686.

    PubMed  CAS  Google Scholar 

  16. Schumacher R, Soos MA, Schlessinger J, Brandenburg D, Siddle K, Ullrich A. Signaling-competent receptor chimeras allow mapping of major insulin receptor binding domain determinants. J Biol Chem 1993; 268: 1087–1094.

    PubMed  CAS  Google Scholar 

  17. Kjeldsen T, Wiberg FC, Andersen AS. Chimeric receptors indicate that phenylalanine 39 is a major contributor to insulin specificity of the insulin receptor. J Biol Chem 1994; 269: 32942–32946.

    PubMed  CAS  Google Scholar 

  18. De Meyts P, Gu JL, Shymko RM, Kaplan BE, Bell GI, Whittaker J. Identification of a ligand-binding region of the human insulin receptor encoded by the second exon of the gene. Mol Endocrinol 1990; 4: 409–416.

    Article  PubMed  Google Scholar 

  19. Williams PF, Mynarcik DC, Yu GQ, Whittaker J. Mapping of an NH2-terminal ligand binding site of the insulin receptor by alanine scanning mutagenesis. J Biol Chem 1995; 270: 3012–3016.

    Article  PubMed  CAS  Google Scholar 

  20. Mynarcik DC, Yu GQ, Whittaker J. Alanine-scanning mutagenesis of a C-terminal ligand binding domain of the insulin receptor a-subunit. J Biol Chem 1996; 271: 2439–2442.

    Article  PubMed  CAS  Google Scholar 

  21. De Meyts P. The structural basis of insulin and insulin-like growth factor-I receptor binding and negative co-operativity, and its relevance to mitogenic versus metabolic signalling. Diabetologia 1994; 37 Suppl 2, 5135–148.

    Google Scholar 

  22. Schäffer L. A model for insulin binding to the insulin receptor. Eur J Biochem 1994; 221: 1127–1132.

    Article  PubMed  Google Scholar 

  23. Lammers R, Gray A, Schlessinger J, Ullrich A. Differential signalling potential of insulin-and IGF-1 receptor cytoplasmic domains. EMBO J 1989; 8: 1369–1375.

    PubMed  CAS  Google Scholar 

  24. Kalloo-Hosein HE, Whitehead JP, Soos M, Tavaré JM, Siddle K, O’Rahilly S. Differential signaling to glycogen synthesis by the intracellular domain of the insulin versus the insulin-like growth factor-1 receptor. Evidence from studies of TrkC-chimeras. J Biol Chem 1997; 272: 24325–24332.

    Article  PubMed  CAS  Google Scholar 

  25. Tavaré JM, Siddle K. Mutational analysis of insulin receptor function: consensus and controversy. Biochim Biophys Acta 1993; 1178: 21–39.

    Article  PubMed  Google Scholar 

  26. Tartare S, Mothe I, Kowalski-Chauvel A, Breittmayer JP, Ballotti R, Van Obberghen E. Signal transduction by a chimeric insulin-like growth factor-1 (IGF-1) receptor having the carboxyl-terminal domain of the insulin receptor. J Biol Chem 1994; 269: 11449–11455.

    PubMed  CAS  Google Scholar 

  27. Faria TN, Blakesley VA, Kato H, Stannard B, LeRoith D, Roberts CT Jr. Role of the carboxyl-terminal domains of the insulin and insulin-like growth factor I receptors in receptor function. J Biol Chem 1994; 269: 13922–13928.

    PubMed  CAS  Google Scholar 

  28. Esposito DL, Blakesley VA, Koval AP, Scrimgeour AG, LeRoith D. Tyrosine residues in the C-terminal domain of the insulin-like growth factor-I receptor mediate mitogenic and tumorigenic signals. Endocrinology 1997; 138: 2979–2988.

    Article  PubMed  CAS  Google Scholar 

  29. Xu B, Bird VG, Miller WT. Substrate specificities of the insulin and insulin-like growth factor 1 receptor tyrosine kinase catalytic domains. J Biol Chem 1995; 270: 29825–29830.

    Article  PubMed  CAS  Google Scholar 

  30. Laviola L, Giorgino F, Chow JC, Baquero JA, Hansen H, Ooi J, Zhu J, Riedel H, Smith RJ. The adapter protein Grb10 associates preferentially with the insulin receptor as compared with the IGF-I receptor in mouse fibroblasts. J Clin Invest 1997; 99: 830–837.

    Article  PubMed  CAS  Google Scholar 

  31. O’Neill TJ, Zhu Y, Gustafson TA. Interaction of MAD2 with the carboxyl terminus of the insulin receptor but not with the IGFIR. Evidence for release from the insulin receptor after activation. J Biol Chem 1997; 272: 10035–10040.

    Article  PubMed  Google Scholar 

  32. Craparo A, Freund R, Gustafson TA. 14–3–3 (e) interacts with the insulin–like growth factor I receptor and insulin receptor substrate I in a phosphoserine–dependent manner. J Biol Chem 1997; 272:1166311669.

    Google Scholar 

  33. Furlanetto RW, Dey BR, Lopaczynski W, Nissley SP. 14–3–3 proteins interact with the insulin–like growth factor receptor but not the insulin receptor. Biochem J 1997; 327: 765 – 771.

    PubMed  CAS  Google Scholar 

  34. Shier P, Watt VM. Tissue-specific expression of the rat insulin receptor-related receptor gene. Mol Endocrinol 1992; 6: 723–729.

    Article  PubMed  CAS  Google Scholar 

  35. Zhang B, Roth RA. The insulin receptor-related receptor. Tissue expression, ligand binding specificity, and signaling capabilities. J Biol Chem 1992; 267: 18320–18328.

    PubMed  CAS  Google Scholar 

  36. Kurachi H, Jobo K, Ohta M, Kawasaki T, Itoh N. A new member of the insulin receptor family, insulin receptor-related receptor, is expressed preferentially in the kidney. Biochem Biophys Res Commun 1992; 187: 934–939.

    Article  PubMed  CAS  Google Scholar 

  37. Mathi SK, Chan J, Watt VM. Insulin receptor-related receptor messenger ribonucleic acid: quantitative distribution and localization to subpopulations of epithelial cells in stomach and kidney. Endocrinology 1995; 136: 4125–4132.

    Article  PubMed  CAS  Google Scholar 

  38. Reinhardt RR, Chin E, Zhang B, Roth RA, Bondy CA. Insulin receptor-related receptor messenger ribonucleic acid is focally expressed in sympathetic and sensory neurons and renal distal tubule cells. Endocrinology 1993; 133: 3–10.

    Article  PubMed  CAS  Google Scholar 

  39. Reinhardt RR, Chin E, Zhang B, Roth RA, Bondy CA. Selective coexpression of insulin receptor-related receptor (IRR) and TRK in NGF-sensitive neurons. J Neurosci 1994; 14: 4674–4683.

    PubMed  CAS  Google Scholar 

  40. Tsujimoto K, Tsuji N, Ozaki K, Ohta M, Itoh N. Insulin receptor-related receptor messenger ribonucleic acid in the stomach is focally expressed in the enterochromaffin-like cells. Endocrinology 1995; 136: 558–561.

    Article  PubMed  CAS  Google Scholar 

  41. Tsujimoto K, Tsuji N, Ozaki K, Minami M, Satoh M, Itoh N. Expression of insulin receptor-related receptor mRNA in the rat brain is highly restricted to forebrain cholinergic neurons. Neurosci Lett 1995; 188: 105–108.

    Article  PubMed  CAS  Google Scholar 

  42. Tsuji N, Tsujimoto K, Takada N, Ozaki K, Ohta M, Itoh N. Expression of insulin receptor-related receptor in the rat brain examined by in situ hybridization and immunohistochemistry. Brain Res Mol Brain Res 1996; 41: 250–258.

    Article  PubMed  CAS  Google Scholar 

  43. Kovacina KS, Roth RA. Characterization of the endogenous insulin receptor-related receptor in neuroblastomas. J Biol Chem 1995; 270: 1881–1887.

    Article  PubMed  CAS  Google Scholar 

  44. Jui HY, Suzuki Y, Accili D, Taylor SI. Expression of a cDNA encoding the human insulin receptor-related receptor. J Biol Chem 1994; 269: 22446–22452.

    PubMed  CAS  Google Scholar 

  45. Seino S, Bell GI. Alternative splicing of human insulin receptor messenger RNA. Biochem Biophys Res Commun 1989; 159: 312–316.

    Article  PubMed  CAS  Google Scholar 

  46. Goldstein BJ, Dudley AL. Heterogeneity of messenger RNA that encodes the rat insulin receptor is limited to the domain of exon 11. Analysis by RNA heteroduplex mapping, amplification of cDNA, and in vitro translation. Diabetes 1992; 41: 1293–1300.

    Article  PubMed  CAS  Google Scholar 

  47. Kenner KA, Kusari J, Heidenreich KA. cDNA sequence analysis of the human brain insulin receptor. Biochem Biophys Res Commun 1995; 217: 304–312.

    Article  PubMed  CAS  Google Scholar 

  48. Moller DE, Yokota A, Caro JF, Flier JS. Tissue-specific expression of two alternatively spliced insulin receptor mRNAs in man. Mol Endocrinol 1989; 3: 1263–1269.

    Article  PubMed  CAS  Google Scholar 

  49. Goldstein BJ, Dudley AI. The rat insulin receptor: primary structure and conservation of tissue-specific alternative messenger RNA splicing. Mol Endocrinol 1990; 4: 235–244.

    Article  PubMed  CAS  Google Scholar 

  50. Benecke H, Flier JS, Moller DE. Alternatively spliced variants of the insulin receptor protein. Expression in normal and diabetic human issues. J Clin Invest 1992; 89: 2066–2070.

    Article  PubMed  CAS  Google Scholar 

  51. Mosthaf L, Grako K, Dull TJ, Coussens L, Ullrich A, McClain DA. Functionally distinct insulin receptors generated by tissue-specific alternative splicing. EMBO J 1990; 9: 2409–2413.

    PubMed  CAS  Google Scholar 

  52. Yamaguchi Y, Flier JS, Yokota A, Benecke H, Backer JM, Moller DE. Functional properties of two naturally occurring isoforms of the human insulin receptor in Chinese hamster ovary cells. Endocrinology 1991; 129: 2058–2066.

    Article  PubMed  CAS  Google Scholar 

  53. Vogt B, Carrascosa JM, Ermel B, Ullrich A, Häring HU. The two isotypes of the human insulin receptor (HIR-A and HIR-B) follow different internalization kinetics. Biochem Biophys Res Commun 1991; 177: 1013–1018.

    Article  PubMed  CAS  Google Scholar 

  54. McClain DA. Different ligand affinities of the two human insulin receptor splice variants are reflected in parallel changes in sensitivity for insulin action. Mol Endocrinol 1991; 5: 734–739.

    Article  PubMed  CAS  Google Scholar 

  55. Kellerer M, Lammers R, Ermel B, Tippmer S, Vogt B, Obermaier-Kusser B, Ullrich A, Häring HU. Distinct a-subunit structures of human insulin receptor A and B variants determine differences in tyrosine kinase activities. Biochemistry 1992; 31: 4588–4596.

    Article  PubMed  CAS  Google Scholar 

  56. Soos MA, Whittaker J, Lammers R, Ullrich A, Siddle K. Receptors for insulin and insulin-like growth factor-I can form hybrid dimers. Characterisation of hybrid receptors in transfected cells. Biochem J 1990; 270: 383–390.

    PubMed  CAS  Google Scholar 

  57. Yamaguchi Y, Flier JS, Benecke H, Ransil BJ, Moller DE. Ligand-binding properties of the two isoforms of the human insulin receptor. Endocrinology 1993; 132: 1132–1138.

    Article  PubMed  CAS  Google Scholar 

  58. Morrione A, Valentinis B, Xu SQ, Yumet G, Louvi A, Efstratiadis A, Baserga R. Insulin-like growth factor II stimulates cell proliferation through the insulin receptor. Proc Natl Acad Sci USA 1997; 94: 3777–3782.

    Article  PubMed  CAS  Google Scholar 

  59. Louvi A, Accili D, Efstratiadis A. Growth-promoting interaction of IGF-II with the insulin receptor during mouse embryonic development. Dev Biol 1997; 189: 33–48.

    Article  PubMed  CAS  Google Scholar 

  60. Abbott AM, Bueno R, Pedrini MT, Murray JM, Smith RJ. Insulin-like growth factor I receptor gene structure. J Biol Chem 1992; 267: 10759–10763.

    PubMed  CAS  Google Scholar 

  61. Pedrini MT, Giorgino F, Smith RJ. cDNA cloning of the rat IGF I receptors: structural analysis of rat and human IGF I and insulin receptors reveals differences in alternative splicing and receptor-domain conservation. Biochem Biophys Res Commun 1994; 202: 1038–1046.

    Article  PubMed  CAS  Google Scholar 

  62. Yee D, Lebovic GS, Marcus RR, Rosen N. Identification of an alternate type I insulin-like growth factor receptor 13 subunit mRNA transcript. J Biol Chem 1989; 264: 21439–21441.

    PubMed  CAS  Google Scholar 

  63. Condorelli G, Bueno R, Smith RJ. Two alternatively spliced forms of the human insulin-like growth factor I receptor have distinct biological activities and internalization kinetics. J Biol Chem 1994; 269: 8510–8516.

    PubMed  CAS  Google Scholar 

  64. Itoh N, Jobo K, Tsujimoto K, Ohta M, Kawasaki T. Two truncated forms of rat insulin receptor-related receptor. J Biol Chem 1993; 268: 17983–17986.

    PubMed  CAS  Google Scholar 

  65. Hintz RL, Thorsson AV, Enberg G, Hall K. IGF-II binding on human lymphoid cells: demonstration of a common high affinity receptor for insulin like peptides. Biochem Biophys Res Commun 1984; 118: 774–782.

    Article  PubMed  CAS  Google Scholar 

  66. Misra P, Hintz RL, Rosenfeld RG. Structural and immunological characterization of insulin-like growth factor II binding to IM-9 cells. J Clin Endocrinol Metab 1986; 63: 1400–1405.

    Article  PubMed  CAS  Google Scholar 

  67. Jonas HA, Newman JD, Harrison LC. An atypical insulin receptor with high affinity for insulin-like growth factors copurified with placental insulin receptors. Proc Natl Acad Sci USA 1986; 83: 41244128.

    Google Scholar 

  68. Tollefsen SE, Thompson K, Petersen DJ. Separation of the high affinity insulin-like growth factor I receptor from low affinity binding sites by affinity chromatography. J Biol Chem 1987; 262: 1646116469.

    Google Scholar 

  69. Jonas HA, Cox AJ, Harrison LC. Delineation of atypical insulin receptors from classical insulin and type I insulin-like growth factor receptors in human placenta. Biochem J 1989; 257: 101–107.

    PubMed  CAS  Google Scholar 

  70. Jonas HA, Cox AJ. Insulin-like growth factor binding to the atypical insulin receptors of a human lymphoid-derived cell line (IM-9). Biochem J 1990; 266: 737–742.

    PubMed  CAS  Google Scholar 

  71. Jonas HA, Eckardt GS, Clark S. Expression of atypical and classical insulin receptors in Chinese hamster ovary cells transfected with cloned cDNA for the human insulin receptor. Endocrinology 1990; 127: 1301–1309.

    Article  PubMed  CAS  Google Scholar 

  72. Burant CF, Treutelaar MK, Allen KD, Sens DA, Buse MG. Comparison of insulin and insulin-like growth factor I receptors from rat skeletal muscle and L-6 myocytes. Biochem Biophys Res Commun 1987; 147: 100–107.

    Article  PubMed  CAS  Google Scholar 

  73. Waldbillig RJ, Chader GJ. Anomalous insulin-binding activity in the bovine neural retina: a possible mechanism for regulation of receptor binding specificity. Biochem Biophys Res Commun 1988; 151: 1105–1112.

    Article  PubMed  CAS  Google Scholar 

  74. Milazzo G, Yip CC, Maddux BA, Vigneri R, Goldfine ID. High-affinity insulin binding to an atypical insulin-like growth factor-I receptor in human breast cancer cells. J Clin Invest 1992; 89: 899–908.

    Article  PubMed  CAS  Google Scholar 

  75. Germain-Lee EL, Janicot M, Lammers R, Ullrich A, Casella SJ. Expression of a type I insulin-like growth factor receptor with low affinity for insulin-like growth factor II. Biochem J 1992; 281: 413–417.

    PubMed  CAS  Google Scholar 

  76. Soos MA, Field CE, Navé BT, Siddle K. Hybrid and atypical insulin-like growth factor receptors. In: Baxter RC, Gluckman PD, Rosenfeld RG, eds. The Insulin-Like Growth Factors and Their Regulatory Proteins. Elsevier, Amsterdam, 1994, pp. 95–106.

    Google Scholar 

  77. Soos MA, Siddle K. Atypical ligand binding to IGF-I receptors reflects a high affinity state of solubilised receptors, in preparation.

    Google Scholar 

  78. Soos MA, Field CE, Lammers R, Ullrich A, Zhang B, Roth RA, Andersen AS, Kjeldsen T, Siddle K. A panel of monoclonal antibodies for the type I insulin-like growth factor receptor. Epitope mapping, effects on ligand binding, and biological activity. J Biol Chem 1992; 267: 12955–12963.

    PubMed  CAS  Google Scholar 

  79. Poretsky L, Kalin MF. The gonadotropic function of insulin. Endocr Rev 1987; 8: 132–141.

    Article  PubMed  CAS  Google Scholar 

  80. Fradkin JE, Eastman RC, Lesniak MA, Roth J. Specificity spillover at the hormone receptor-exploring its role in human disease. N Engl J Med 1989; 320: 640–645.

    Article  PubMed  CAS  Google Scholar 

  81. Schlessinger J. Signal transduction by allosteric receptor oligomerization. Trends Biochem Sci 1988; 13: 443–447.

    Article  PubMed  CAS  Google Scholar 

  82. Heldin CH. Dimerization of cell surface receptors in signal transduction. Cell 1995; 80: 213–223.

    Article  PubMed  CAS  Google Scholar 

  83. Soos MA, Siddle K Immunological relationships between receptors for insulin and insulin-like growth factor I. Evidence for structural heterogeneity of insulin-like growth factor I receptors involving hybrids with insulin receptors. Biochem J 1989; 263: 553–563.

    PubMed  CAS  Google Scholar 

  84. Jonas HA, Harrison LC. The human placenta contains two distinct binding and immunoreactive species of insulin-like growth factor-I receptors. J Biol Chem 1985; 260: 2288–2294.

    PubMed  CAS  Google Scholar 

  85. Morgan DO, Roth RA. Identification of a monoclonal antibody which can distinguish between two distinct species of the type I receptor for insulin-like growth factor. Biochem Biophys Res Commun 1986; 138: 1341–1347.

    Article  PubMed  CAS  Google Scholar 

  86. Moxham CP, Duronio V, Jacobs S. Insulin-like growth factor I receptor 13-subunit heterogeneity. Evidence for hybrid tetramers composed of insulin-like growth factor I and insulin receptor heterodimers. J Biol Chem 1989; 264: 13238–13244.

    PubMed  CAS  Google Scholar 

  87. Garofalo RS, Rosen OM. Insulin and insulinlike growth factor-1 (IGF-1) receptors during central nervous system development: expression of two immunologically distinct IGF-1 receptor (3 subunits. Mol Cell Biol 1989; 9: 2806–2817.

    PubMed  CAS  Google Scholar 

  88. Jacobs S, Kull FC, Earp HS, Svoboda ME, Van Wyk JJ, Cuatrecasas P. Somatomedin-C stimulates the phosphorylation of the 13-subunit of its own receptor. J Biol Chem 1983; 258: 9581–9584.

    PubMed  CAS  Google Scholar 

  89. Yu KT, Peters MA, Czech MP. Similar control mechanisms regulate the insulin and type I insulin-like growth factor receptor kinases. Affinity-purified insulin-like growth factor I receptor kinase is activated by tyrosine phosphorylation of its (3 subunit. J Biol Chem 1986; 261: 11341–11349.

    PubMed  CAS  Google Scholar 

  90. Morgan DO, Jarnagin K, Roth RA. Purification and characterization of the receptor for insulin-like growth factor I. Biochemistry 1986; 25: 5560–5564.

    Article  PubMed  CAS  Google Scholar 

  91. Kadowaki T, Koyasu S, Nishida E, Tobe K, Izumi T, Takaku F, Sakai H, Yahara I, Kasuga M. Tyrosine phosphorylation of common and specific sets of cellular proteins rapidly induced by insulin, insulin-like growth factor I, and epidermal growth factor in an intact cell. J Biol Chem 1987; 262: 7342–7350.

    PubMed  CAS  Google Scholar 

  92. Shemer J, Adamo M, Wilson GL, Heffez D, Zick Y, LeRoith D. Insulin and insulin-like growth factor-I stimulate a common endogenous phosphoprotein substrate (pp185) in intact neuroblastoma cells. J Biol Chem 1987; 262: 15476–15482.

    PubMed  CAS  Google Scholar 

  93. Treadway JL, Morrison BD, Goldfine ID, Pessin JE. Assembly of insulin insulin-like growth factor-1 hybrid receptors in vitro. J Biol Chem 1989; 264: 21450–21453.

    PubMed  CAS  Google Scholar 

  94. Jul HY, Accili D, Taylor SI. Characterization of a hybrid receptor formed by dimerization of the insulin receptor-related (IRR) with the insulin receptor (IR): coexpression of cDNAs encoding human IRR and human IR in NIH-3T3 cells. Biochemistry 1996; 35: 14326–14330.

    Article  Google Scholar 

  95. Soos MA, Field CE, Siddle K. Purified hybrid insulin insulin-like growth factor-I receptors bind insulin-like growth factor-I, but not insulin, with high affinity. Biochem J 1993; 290: 419–426.

    PubMed  CAS  Google Scholar 

  96. Kasuya J, Paz IB, Maddux BA, Goldfine ID, Hefta SA, Fujita-Yamaguchi Y. Characterization of human placental insulin-like growth factor-I insulin hybrid receptors by protein microsequencing and purification. Biochemistry 1993; 32: 13531–13536.

    Article  PubMed  CAS  Google Scholar 

  97. Frattali AL, Pessin JE. Relationship between a-subunit ligand occupancy and 13-subunit autophosphorylation in insulin insulin-like growth factor-1 hybrid receptors. J Biol Chem 1993; 268: 73937400.

    Google Scholar 

  98. Hammond BJ, Tikerpae J, Smith GD. An evaluation of the cross-linking model for the interaction of insulin with its receptor. Am J Physiol 1997; 272: E1136 - E1144.

    PubMed  CAS  Google Scholar 

  99. Böni-Schnetzler M, Rubin JB, Pilch PF. Structural requirements for the transmembrane activation of the insulin receptor kinase. J Biol Chem 1986; 261: 15281–15287.

    PubMed  Google Scholar 

  100. Böni-Schnetzler M, Scott W, Waugh SM, DiBella E, Pilch PF. The insulin receptor. Structural basis for high affinity ligand binding. J Biol Chem 1987; 262: 8395–8401.

    PubMed  Google Scholar 

  101. Sweet LJ, Morrison BD, Pessin JE. Isolation of functional aß heterodimers from the purified human placental alpha x2132 heterotetrameric insulin receptor complex. A structural basis for insulin binding heterogeneity. J Biol Chem 1987; 262: 6939–6942.

    PubMed  CAS  Google Scholar 

  102. Tollefsen SE, Thompson K. The structural basis for insulin-like growth factor I receptor high affinity binding. J Biol Chem 1988; 263: 16267–16273.

    PubMed  CAS  Google Scholar 

  103. Jonas HA, Harrison LC. Disulphide reduction alters the immunoreactivity and increases the affinity of insulin-like growth-factor-I receptors in human placenta. Biochem J 1986; 236: 417–423.

    PubMed  CAS  Google Scholar 

  104. Feltz SM, Swanson ML, Wemmie JA, Pessin JE. Functional properties of an isolated a43 heterodimeric human placenta insulin-like growth factor 1 receptor complex. Biochemistry 1988; 27: 3234–3242.

    Article  PubMed  CAS  Google Scholar 

  105. Zhong P, Cara JF, Tager HS. Importance of receptor occupancy, concentration differences, and ligand exchange in the insulin-like growth factor I receptor system. Proc Natl Acad Sci USA 1993; 90: 114511 1455.

    Google Scholar 

  106. Christoffersen CT, Bornfeldt KE, Rotella CM, Gonzales N, Vissing H, Shymko RM, ten Hoeve J, Groffen J, Heisterkamp N, De Meyts P. Negative cooperativity in the insulin-like growth factor-I receptor and a chimeric IGF-I insulin receptor. Endocrinology 1994; 135: 472–475.

    Article  PubMed  CAS  Google Scholar 

  107. Seely BL, Reichart DR, Takata Y, Yip C, Olefsky JM. A functional assessment of insulin insulin-like growth factor-I hybrid receptors. Endocrinology 1995; 136: 1635–1641.

    Article  PubMed  CAS  Google Scholar 

  108. Baker J, Liu JP, Robertson EJ, Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell 1993; 75: 73–82.

    PubMed  CAS  Google Scholar 

  109. Joshi RL, Lamothe B, Cordonnier N, Mesbah K, Monthioux E, Jami J, Bucchini D. Targeted disruption of the insulin receptor gene in the mouse results in neonatal lethality. EMBO J 1996; 15: 1542–1547.

    PubMed  CAS  Google Scholar 

  110. Accili D, Drago J, Lee EJ, Johnson MD, Cool MH, Salvatore P, Asico D, José PA, Taylor SI, Westphal H. Early neonatal death in mice homozygous for a null allele of the insulin receptor gene. Nature Genet 1996; 12: 106–109.

    Article  PubMed  CAS  Google Scholar 

  111. Krook A, Brueton L, O’Rahilly S. Homozygous nonsense mutation in the insulin receptor gene in an infant with leprechaunism. Lancet 1993; 342: 277–278.

    Article  PubMed  CAS  Google Scholar 

  112. Wertheimer E, Lu SP, Backeljauw PF, Davenport ML, Taylor SI. Homozygous deletion of the human insulin receptor gene results in leprechaunism. Nature Genet 1993; 5: 71–73.

    Article  PubMed  CAS  Google Scholar 

  113. Wada T, Qian XL, Greene MI. Intermolecular association of the p185neu protein and EGF receptor modulates EGF receptor function. Cell 1990; 61: 1339–1347.

    Article  PubMed  CAS  Google Scholar 

  114. Qian XL, Decker SJ, Greene MI. p185c-neu and epidermal growth factor receptor associate into a structure composed of activated kinases. Proc Natl Acad Sci USA 1992; 89: 1330–1334.

    Article  CAS  Google Scholar 

  115. Sliwkowski MX, Schaefer G, Akita RW, Lofgren JA, Fitzpatrick VD, Nuijens A, Fendly BM, Cerione RA, Vandlen RL, Carraway KL. Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin. J Biol Chem 1994; 269: 14661–14665.

    PubMed  CAS  Google Scholar 

  116. Soltoff SP, Carraway KL, Prigent SA, Gullick WG, Cantley LC. ErbB3 is involved in activation of phosphatidylinositol 3-kinase by epidermal growth factor. Mol Cell Biol 1994; 14: 3550–3558.

    PubMed  CAS  Google Scholar 

  117. Alimandi M, Romano A, Curia MC, Muraro R, Fedi P, Aaronson SA, Di Fiore PP, Kraus MH. Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene 1995; 10: 1813–1821.

    PubMed  CAS  Google Scholar 

  118. Wallasch C, Weiss FU, Niederfellner G, Jallal B, Is sing W, Ullrich A. Heregulin-dependent regulation of HER2 neu oncogenic signaling by heterodimerization with HER3. EMBO J 1995; 14: 4267–4275.

    PubMed  CAS  Google Scholar 

  119. Riese DJ, van Raaij TM, Plowman GD, Andrews GC, Stern DF. The cellular response to neuregulins is governed by complex interactions of the erbB receptor family. Mol Cell Biol 1995; 15: 5770–5776.

    PubMed  CAS  Google Scholar 

  120. Eriksson A, Siegbahn A, Westermark B, Heldin CH, Claesson-Welsh I. PDGF a-and (3-receptors activate unique and common signal transduction pathways. EMBO J 1992; 11: 543–550.

    PubMed  CAS  Google Scholar 

  121. Heidaran MA, Pierce JH, Yu JC, Lombardi D, Artrip JE, Fleming TP, Thomason A, Aaronson SA. Role of a(3 receptor heterodimer formation in 3 platelet-derived growth factor (PDGF) receptor activation by PDGF-AB. J Biol Chem 1991; 266: 20232–20237.

    PubMed  CAS  Google Scholar 

  122. Bailyes EM, Nave BT, Soos MA, Orr SR, Hayward AC, Siddle K. Insulin receptor IGF-I receptor hybrids are widely distributed in mammalian tissues: quantification of individual receptor species by selective immunoprecipitation and immunoblotting. Biochem J 1997; 327: 209–215.

    PubMed  CAS  Google Scholar 

  123. Federici M, Porzio O, Zucaro L, Fusco A, Borboni P, Lauro D, Sesti G. Distribution of insulin insulinlike growth factor-I hybrid receptors in human tissues. Mol Cell Endocrinol 1997; 129: 121–126.

    Article  PubMed  CAS  Google Scholar 

  124. Weiland M, Bahr F, Hohne M, Schurmann A, Zeihm D, Joost HG. The signaling potential of the receptors for insulin and insulin-like growth factor I (IGF-I) in 3T3–L1 adipocytes: comparison of glucose transport activity, induction of oncogene c-fos, glucose transporter mRNA, and DNA-synthesis. J Cell Physiol 1991; 149: 428–435.

    Article  PubMed  CAS  Google Scholar 

  125. Adamo M, Roberts CT Jr, LeRoith D. How distinct are the insulin and insulin-like growth factor I signalling systems? Biofactors 1992; 3: 151–157.

    PubMed  CAS  Google Scholar 

  126. Olson TS, Bamberger MJ, Lane MD. Post-translational changes in tertiary and quaternary structure of the insulin proreceptor. Correlation with acquisition of function. J Biol Chem 1988; 263: 7342–7351.

    PubMed  CAS  Google Scholar 

  127. Waugh SM, DiBella EE, Pilch PF. Isolation of a proteolytically derived domain of the insulin receptor containing the major site of cross-linking binding. Biochemistry 1989; 28: 3448–3455.

    Article  PubMed  CAS  Google Scholar 

  128. Xu QY, Paxton RJ, Fujita-Yamaguchi Y. Substructural analysis of the insulin receptor by microsequence analyses of limited tryptic fragments isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the absence or presence of dithiothreitol. J Biol Chem 1990; 265: 1867318681.

    Google Scholar 

  129. Finn FM, Ridge KD, Hofmann K. Labile disulfide bonds in human placental insulin receptor. Proc Natl Acad Sci USA 1990; 87: 419–423.

    Article  PubMed  CAS  Google Scholar 

  130. Chiacchia KB. Quantitation of the class I disulfides of the insulin receptor. Biochem Biophys Res Commun 1991; 176: 1178–1182.

    Article  PubMed  CAS  Google Scholar 

  131. Sparrow LG, McKern NM, Gorman JJ, Strike PM, Robinson CP, Bentley JD, Ward CW. The disulphide bonds in the C-terminal domains of the human insulin receptor ectodomain. J Biol Chem 1997; 272: 29460–29467.

    Article  PubMed  CAS  Google Scholar 

  132. Schäffer L, Ljungqvist L. Identification of a disulfide bridge connecting the (3-subunits of the extracellular domain of the insulin receptor. Biochem Biophys Res Commun 1992; 189: 650–653.

    Article  PubMed  Google Scholar 

  133. Macaulay SL, Pates M, Hewish DR, Ward CW. Cysteine-524 is not the only residue involved in the formation of disulphide-bonded dimers of the insulin receptor. Biochem J 1994; 303: 575–581.

    PubMed  CAS  Google Scholar 

  134. Valensise H, Liu YY, Federici M, Lauro D, Dell’anna D, Romanini C, Sesti G. Increased expression of low-affinity insulin receptor isoform and insulin insulin-like growth factor-I hybrid receptors in term placenta from insulin-resistant women with gestational hypertension. Diabetologia 1996; 39: 952–960.

    Article  PubMed  CAS  Google Scholar 

  135. Federici M, Zucaro L, Porzio O, Massoud R, Borboni P, Lauro D, Sesti G. Increased expression of insulin insulin-like growth factor-I hybrid receptors in skeletal muscle of noninsulin-dependent diabetes mellitus subjects. J Clin Invest 1996; 98: 2887–2893.

    Article  PubMed  CAS  Google Scholar 

  136. Pandini G, Vigneri R, Costantino A, Ippolito A, Fujita-Yamaguchi Y, Siddle K, Goldfine ID, Belfiore A. Insulin IGF-I hybrid receptors play a major role in IGF-I signalling in breast cancer. Clin Cancer Res, in press.

    Google Scholar 

  137. Garrouste FL, Remade Bonnet MM, Lehmann MM, Marvaldi JL, Pommier GJ. Up-regulation of insulin insulin-like growth factor-I hybrid receptors during differentiation of HT29–D4 human colonic carcinoma cells. Endocrinology 1997; 138: 2021–2032.

    Article  PubMed  CAS  Google Scholar 

  138. Taylor SI, Cama A, Accili D, Barbetti F, Quon MJ, de la Luz Sierra M, Suzuki Y, Koller E, Levy Toledano R, Wertheimer E, Moncada VY, Kadowaki H, Kadowaki T. Mutations in the insulin receptor gene. Endocr Rev 1992; 13: 566–595.

    PubMed  CAS  Google Scholar 

  139. Accili D. Molecular defects of the insulin receptor gene. Diabetes Metab Rev 1995; 11: 47–62.

    Article  PubMed  CAS  Google Scholar 

  140. Treadway JL, Morrison BD, Soos MA, Siddle K, Olefsky J, Ullrich A, McClain DA, Pessin JE. Transdominant inhibition of tyrosine kinase activity in mutant insulin insulin-like growth factor I hybrid receptors. Proc Natl Acad Sci USA 1991; 88: 214–218.

    Article  PubMed  CAS  Google Scholar 

  141. Ota A, Wilson G-L, LeRoith D. Insulin-like growth factor I receptors on mouse neuroblastoma cells. Two (3 subunits are derived from differences in glycosylation. Eur J Biochem 1988; 174: 521–530.

    Article  PubMed  CAS  Google Scholar 

  142. Alexandrides TK, Smith RJ. A novel fetal insulin-like growth factor (IGF) I receptor. Mechanism for increased IGF I- and insulin-stimulated tyrosine kinase activity in fetal muscle. J Biol Chem 1989; 264: 12922–12930.

    Google Scholar 

  143. Kellerer M, Obermaier-Kusser B, Ermel B, Wallner U, Häring HU, Petrides PE. An altered IGF-I receptor is present in human leukemic cells. J Biol Chem 1990; 265: 9340–9345.

    PubMed  CAS  Google Scholar 

  144. Hainaut P, Kowalski A, Giorgetti S, Baron V, Van Obberghen E. Insulin and insulin-like growth-factorI (IGF-I) receptors in Xenopus laevis oocytes. Comparison with insulin receptors from liver and muscle. Biochem J 1991; 273: 673–678.

    PubMed  CAS  Google Scholar 

  145. Domeyne A, Pinset C, Montarras D, Garandel V, Rosenfeld RG, Barenton B. Preferential binding of insulin-like growth factor-II (IGF-II) to a putative a2132 IGF-II receptor type in C2 myoblasts. Eur J Biochem 1992; 208: 273–279.

    Article  PubMed  CAS  Google Scholar 

  146. Garofalo RS, Barenton B. Functional and immunological distinction between insulin-like growth factor I receptor subtypes in KB cells. J Biol Chem 1992; 267: 11470–11475.

    PubMed  CAS  Google Scholar 

  147. Barenton B, Domeyne A, Garandel V, Garofalo RS. A developmentally regulated form of insulin-like growth factor receptor a-subunit in C2 myoblasts exhibiting altered requirements for differentiation. Endocrinology 1993; 133: 651–660.

    Article  PubMed  CAS  Google Scholar 

  148. Alexandrides TK, Chen JH, Bueno R, Giorgino F, Smith RJ. Evidence for two insulin-like growth factor I receptors with distinct primary structure that are differentially expressed during development. Regul Pept 1993; 48: 279–290.

    Article  PubMed  CAS  Google Scholar 

  149. Moss AM, Livingston JN. Distinct (3-subunits are present in hybrid insulin-like-growth-factor-1 receptors in the central nervous system. Biochem J 1993; 294: 685–692.

    PubMed  CAS  Google Scholar 

  150. Beguinot F, Smith RJ, Kahn CR, Maron R, Moses AC, White MF. Phosphorylation of insulin-like growth factor I receptor by insulin receptor tyrosine kinase in intact cultured skeletal muscle cells. Biochemistry 1988; 27: 3222–3228.

    Article  PubMed  CAS  Google Scholar 

  151. Heidenreich KA, Brandenburg D. Oligosaccharide heterogeneity of insulin receptors. Comparison of N-linked glycosylation of insulin receptors in adipocytes and brain. Endocrinology 1986; 118: 1835.

    Article  PubMed  CAS  Google Scholar 

  152. Whittaker J, Okamoto AK, Thys R, Bell GI, Steiner DF, Hofmann CA. High-level expression of human insulin receptor cDNA in mouse NIH 3T3 cells. Proc Natl Acad Sci USA 1987; 84: 5237–5241.

    Article  PubMed  CAS  Google Scholar 

  153. Ganderton RH, Stanley KK, Field CE, Coghlan MP, Soos MA, Siddle K. A monoclonal anti-peptide antibody reacting with the insulin receptor 13-subunit. Characterization of the antibody and its epitope and use in immunoaffinity purification of intact receptors. Biochem J 1992; 288: 195–205.

    PubMed  CAS  Google Scholar 

  154. Bajaj M, Waterfield MD, Schlessinger J, Taylor WR, Blundell T. On the tertiary structure of the extracellular domains of the epidermal growth factor and insulin receptors. Biochim Biophys Acta 1987; 916: 220–226.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Kenneth Siddle PhD
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  2. Maria A. Soos PhD
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Editors and Affiliations

  1. Department of Pediatrics, School of Medicine, Oregon Health Sciences University, Portland, OR, USA

    Ron G. Rosenfeld MD

  2. Oregon Health Sciences University, Portland, OR, USA

    Charles T. Roberts Jr. PhD

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Siddle, K., Soos, M.A. (1999). Alternative IGF-Related Receptors. In: Rosenfeld, R.G., Roberts, C.T. (eds) The IGF System. Contemporary Endocrinology, vol 17. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-712-3_9

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  • DOI: https://doi.org/10.1007/978-1-59259-712-3_9

  • Publisher Name: Humana Press, Totowa, NJ

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