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IGF-I Receptor Function

Transducing the IGF-I Signal into Intracellular Events

  • Chapter
The IGF System

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

Abstract

The insulin-like growth factor (IGF)-I receptor, or type 1 IGF receptor, is a transmembrane tyrosine kinase receptor that mediates the majority of the biological actions of IGF-I and IGF-II (1,2). The ligands, IGF-I or IGF-II, bind to the extracellular domain of the receptor and initiate a conformational change that is transmitted to the intracellular domain. The receptor is then autophosphorylated on several intracellular tyrosine residues. The tyrosine-phosphorylated receptor is then fully active as a tyrosine kinase toward endogenous substrates. Both IGF-I and IGF-II circulate bound to IGF binding proteins (IGFBPs) (3). The IGF—IGFBP complexes either enhance or inhibit IGF action in a tissue-specific manner The known roles of the IGFBPs are presented in other chapters. Whereas the IGFBPs regulate the activation of the receptor by the binding of its cognate ligands, IGF-I receptor activation constitutes the ultimate requisite for the transduction of IGF-mediated signals.

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References

  1. LeRoith D, Adamo M, Werner H, Roberts CT Jr. Insulin-like growth factors and their receptors as growth regulators in normal physiology and pathological states. Trends Endocrinol Metab 1991; 2: 134–139.

    Article  CAS  Google Scholar 

  2. Nissley P, Lopaczynski W. Insulin-like growth factor receptors. Growth Factors 1991; 5: 29–49.

    Article  CAS  PubMed  Google Scholar 

  3. Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 1995; 16: 3–24.

    CAS  PubMed  Google Scholar 

  4. LeRoith D, Werner H, Beitner-Johnson D, Roberts CT Jr. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 1995; 16: 143–163.

    CAS  PubMed  Google Scholar 

  5. Ullrich A, Gray A, Ram 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.

    CAS  PubMed  Google Scholar 

  6. Jacobs S, Kull FC Jr, Cuatrecasas P. Monensin blocks the maturation of receptors for insulin and somatomedin C: identification of receptor precursors. PNAS 1983; 80: 1228–1231.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  8. Condorelli G, Smith RJ. Two alternatively spliced forms of the IGF-I receptor have distinct biological activities and hormone-induced internalization rates. Exp Clin Endocrinol 1993; 101: 95–97.

    Google Scholar 

  9. 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.

    CAS  PubMed  Google Scholar 

  10. Moss AM, Livingston JN. Distinct 0-subunits are present in hybrid insulin-like-growth-factor-I receptors in the central nervous system. Biochem J 1993; 294: 685–692.

    CAS  PubMed  Google Scholar 

  11. Alexandrides TK, Moses AC, Smith RJ. Developmental expression of receptors for insulin, insulin-like growth factor I (IGF-I), and IGF-II in rat skeletal muscle. Endocrinology 1989; 124: 1064–1076.

    Article  CAS  PubMed  Google Scholar 

  12. 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 

  13. Alexandrides TK, Chen J-H, 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  CAS  PubMed  Google Scholar 

  14. Kellerer M, Obernmaier-Kusser B, Ermal B, Wallner U, Haring H-U, Petrides P. An altered IGF-I receptor is present in human leukemic cells. J Biol Chem 1990; 265: 9340–9345.

    CAS  PubMed  Google Scholar 

  15. Garofalo RS, Barenton B. Functional and immunological distinction between insulin-like growth factor I receptor subtypes in KB cells. J Biol Chem 1992; 276: 1140–11475.

    Google Scholar 

  16. Barenton B, Domeyne A, Garandel V, Garofalo RS. A developmentally regulated form of insulin-like growth factor receptor 13-subunit in C2 myoblasts exhibiting altered requirements for differentiation. Endocrinology 1993; 133: 651–660.

    Article  CAS  PubMed  Google Scholar 

  17. 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 a2132IGF-II receptor type C2 myoblasts. Eur J Biochem 1992; 208: 273–279.

    Article  CAS  PubMed  Google Scholar 

  18. Soos MA, Siddle K Immunological relationships betwen 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.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  20. 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: 419–425.

    CAS  PubMed  Google Scholar 

  21. Kasuya J, Paz B, Maddux AB, 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  CAS  PubMed  Google Scholar 

  22. Moxham CP, Duronio V, Jacobs S. Insulin-like growth factor I receptor (3 subunit heterogeneity. Evidence for hybrid tetramers composed of insulin-like growth factor I and insulin receptor heterodimers. J Biol Chem 1989; 264: 13238–13244.

    CAS  PubMed  Google Scholar 

  23. Moxham CP, Jacobs S. Insulin IGF-I receptor hybrids: a mechanism for increasing receptor diversity. J Cell Biochem 1992; 48: 136–140.

    Article  CAS  PubMed  Google Scholar 

  24. Moxham CP, Jacobs S. Insulin-like growth factor receptors. In: Schofield PN, ed. The Insulin-Like Growth Factors. Structure and Biological Functions. Oxford University Press, Oxford, 1992, pp. 80–109.

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  26. Ullrich A, Bell JR, Chen EY, Herrera R, Petruzzelli LM, Dull TJ, Gray A, Coussen L, Liao Y-C, 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  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  28. Ullrich A, Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell 1990; 61: 203–212.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  31. Andersen AS, Kjeldsen T, Wiberg FC, Christensen PM, Rasmussen JS, Norris K, Moller KB, Moller NPH. Changing the insulin receptor to possess insulin-like growth factor I ligand specificity. Biochemistry 1990; 29: 7363–7366.

    Article  CAS  PubMed  Google Scholar 

  32. Kjeldsen T, Andersen AS, Wiberg FC, Rasmussen JS, Schaffer L, Balschmidt P, Moller KB, Moller NPH. The ligand specificities of the insulin receptor and the insulin-like growth factor I receptor reside in different regions of a common binding site. PNAS 1991; 88: 4404–4408.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  34. 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. J Biol Chem 1992; 267: 12955–12963.

    CAS  PubMed  Google Scholar 

  35. Andersen AS, Kjeldsen T, Wiberg FC. Identification of determinants that confer ligand specificity on the insulin receptor. J Biol Chem 1992; 267: 13581–13686.

    Google Scholar 

  36. Zhang B, Roth RA. A region of the insulin receptor important for ligand binding (residues 450–601) is recognised by patients autoimmune antibodies and inhibitory monoclonal antibodies. PNAS 1991; 88: 9858–9862.

    Article  CAS  PubMed  Google Scholar 

  37. 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.

    CAS  PubMed  Google Scholar 

  38. Mynarcik DC, Williams PF, Schaffer L, Yu GQ, Whittaker J. Identification of common ligand binding determinants of the insulin and insulin-like growth factor 1 receptors. Insights into mechanisms of ligand binding. J Biol Chem 1997; 272: 18650–18655.

    CAS  Google Scholar 

  39. Shoelson SE, White MF, Kahn CR. Tryptic activation of the insulin receptor. J Biol Chem 1988; 263: 4852–4860.

    CAS  PubMed  Google Scholar 

  40. Liu D, Rutter WJ, Wang L-H. Enhancement of transforming potential of human insulin-like growth factor I receptor by N-terminal truncation and fusion to avian sarcoma virus UR2 gag sequence. J Virol 1992; 66: 374–385.

    CAS  PubMed  Google Scholar 

  41. Liu D, Rutter WJ, Wang L-H. Modulating effects of the extracellular sequence of the human insulinlike growth factor I receptor on its transforming and tumorigenic potential. J Virol 1993; 67: 9–18.

    CAS  PubMed  Google Scholar 

  42. Takahashi K, Yonezawa K, Nishimoto I. Insulin-like growth factor-I receptor activated by a transmembrane mutation. J Biol Chem 1995; 270: 19041–19045.

    Article  CAS  PubMed  Google Scholar 

  43. Pilch PF. The insulin-like growth factor-I receptor kinase. In: Moudgil VK, ed. Receptor Phosphorylation. CRC Press, Boca Raton, FL, 1989, pp. 135–150.

    Google Scholar 

  44. Kato H, Faria TN, Stannard B, Roberts CT Jr, LeRoith D. Role of tyrosine kinase activity in signal transduction by the insulin-like growth factor-I (IGF-I) receptor: characterization of kinase-deficient IGF-I receptors and the action of an IGF-I-mimetic antibody (ŒIR-3). J Biol Chem 1993; 268: 2655 2661.

    Google Scholar 

  45. Grönborg M, Wulff BS, Rasmussen JS, Kjeldsen T, Gammeltoft S. Structure-function relationship of the insulin-like growth factor I receptor tyrosine kinase. J Biol Chem 1993; 268: 23435–23440.

    PubMed  Google Scholar 

  46. Kato H, Faria TN, Stannard B, Roberts CT Jr, LeRoith D. Essential role of tyrosine residues 1131,1135, and 1136 of the insulin-like growth factor-I (IGF-I) receptor in IGF-I action. Mol Endocrinol 1994; 8: 40–50.

    Article  CAS  PubMed  Google Scholar 

  47. Li S, Ferber A, Miura M, Baserga R. Mitogenicity and transforming activity of the insulin-like growth factor-I receptor with mutations in the tyrosine kinase domain. J Biol Chem 1994; 269: 32558–32564.

    CAS  PubMed  Google Scholar 

  48. Hernandez-Sanchez C, Blakesley VA, Kalebic T, Helman L, LeRoith D. The role of the tyrosine kinase domain of the insulin-like growth factor-I receptor in intracellular signaling, cellular proliferation, and tumorigenesis. J Biol Chem 1995; 270: 29176–29181.

    Article  CAS  PubMed  Google Scholar 

  49. Stannard B, Blakesley VA, Kato H, Roberts CT Jr, LeRoith D. Single tyrosine substitution in the insulin-like growth factor-I receptor inhibits biological activity and ligand-induced receptor internalization. Endocrinology 1995; 136: 4918–4924.

    Article  CAS  PubMed  Google Scholar 

  50. Jiang Y, Chan JLK, Zong CS, Wang L. Effect of tyrosine mutations on the kinase activity of transforming potential of an oncogenic human insulin-like growth factor I receptor. J Biol Chem 1996; 271: 160–167.

    Article  CAS  PubMed  Google Scholar 

  51. Chen J, Hanafusa T, Wang L-H. Ala-Gly mutation in the putative catalytic loop confers temperature sensitivity on Ros, insulin receptor, and insulin-like growth factor I receptor protein-tyrosine kinases. Proc Natl Acad Sci USA 1994; 91: 321–325.

    Article  CAS  PubMed  Google Scholar 

  52. Blakesley VA, Kato H, Roberts CT Jr, LeRoith D. Mutation of a conserved amino acid residue (tryptophan 1173) in the tyrosine kinase domain of the IGF-I receptor abolishes autophosphorylation but does not eliminate biologic function. J Biol Chem 1995; 270: 2764–2769.

    Article  CAS  PubMed  Google Scholar 

  53. White MF, Kahn CR. The insulin signaling system. J Biol Chem 1994; 269: 1–4.

    CAS  PubMed  Google Scholar 

  54. Hsu D, Knudson PE, Zapf A, Rolband GC, Olefsky JM. NPXY motif in the insulin-like growth factor-I receptor is required for efficient ligand-mediated receptor internalization and biological signaling. Endocrinology 1994; 134: 744–750.

    Article  CAS  PubMed  Google Scholar 

  55. Prager D, Li H-L, Yamasaki H, Melmed S. Human insulin-like growth factor I receptor internalization. Role of the juxtamembrane domain. J Biol Chem 1994; 269: 11934–11937.

    CAS  PubMed  Google Scholar 

  56. Liu D, Zong CS, Wang L-H. Distinctive effects of the carboxyl-terminal sequence of the insulin-like growth factor I receptor on its signaling functions. J Virol 1993; 67: 6835–6840.

    CAS  PubMed  Google Scholar 

  57. Surmacz E, Sell C, Swantek J, Kato H, Roberts CT Jr, LeRoith D, Baserga R. Dissociation of mitogenesis and transforming activity by C-terminal truncation of the insulin-like growth factor I receptor. Exp Cell Res 1995; 218: 370–380.

    Article  CAS  PubMed  Google Scholar 

  58. Miura M, Surmacz E, Burgaud J-L, Baserga R. Different effects on mitogenesis and transformation of a mutation at tyrosine 1251 of the insulin-like growth factor 1 receptor. J Biol Chem 1995; 270: 226392 2644.

    Google Scholar 

  59. Blakesley VA, Kalebic T, Heiman LJ, Stannard B, Faria TN, Roberts CT Jr, LeRoith D. Tumorigenic and mitogenic capacities are reduced in transfected fibroblasts expressing mutant insulin-like growth factor (IGF)-I receptors. The role of tyrosine residues 1250, 1251, and 1316 in the carboxy-terminus of the IGF-I receptor. Endocrinology 1996; 137: 410–417.

    Google Scholar 

  60. Li S, Resnicoff M, Baserga R. Effect of mutations at serines 1280–1283 on the mitogenic and transforming activities of the insulin-like growth factor-I receptor. J Biol Chem 1996; 271: 12254–12260.

    Article  CAS  PubMed  Google Scholar 

  61. Lewis RE, Wu GP, Macdonald RG, Czech M. Insulin sensitive phosphorylation of serine 1293 1294 on the human insulin receptor by a tightly associated serine kinase. J Biol Chem 1990; 265: 947–954.

    CAS  PubMed  Google Scholar 

  62. Peraldi P, Hauguel-de Mouzon S, Alengrin F, Van Obberghen E. Dephosphorylation of human insulin-like growth factor I (IGF-I) receptors by membrane-associated tyrosine phosphatases. Biochem J 1992; 285: 71–78.

    CAS  PubMed  Google Scholar 

  63. van der Geer P, Hunter T, Lindberg RA. Receptor protein-tyrosine kinases and their signal transduction pathways. Annu Rev Cell Biol 1994; 10: 251–337.

    Article  PubMed  Google Scholar 

  64. Way BA, Mooney RA. Activation of phosphatidylinositol-3-kinase by platelet-derived growth factor and insulin-like growth factor-I is inhibited by a transmembrane phosphotyrosine phosphatase. J Biol Chem 1993; 269: 26409–26415.

    Google Scholar 

  65. Peterson JE, Jelinek T, Kaleko M, Siddle K, Weber MJ. Phosphorylation and activation of the IGF-I receptor in src-transformed cells. J Biol Chem 1994; 269: 27315–27321.

    CAS  PubMed  Google Scholar 

  66. Ooi J, Yajnik V, Immanuel D, Gordon M, Moskow JJ, Buchberg AM, Margolis B. The cloning of Grb10 reveals a new family of SH2 domain proteins. Oncogene 1995; 10: 1621–1630.

    CAS  PubMed  Google Scholar 

  67. Dey BR, Frick K, Lopaczynski W, Nissley SP, Furlanetto RW. Evidence for the direct interaction of the insulin-like growth factor I receptor with IRS-1, Shc, and Grb10. Mol Endocrinol 1996; 10: 631–641.

    Article  CAS  PubMed  Google Scholar 

  68. Morrione A, Valentinis B, Li S, Ooi JYT, Margolis B, Baserga R. Grb10: a new substrate of the insulin-like growth factor I receptor. Cancer Res 1996; 56: 3165–3167.

    CAS  PubMed  Google Scholar 

  69. O’Neill TJ, Rose DW, Pillay TS, Hotta K, Olefsky JM, Gustafson TA. Interaction of a GRB-IR splice variant (a human GRB 10 homolog) with the insulin and insulin-like growth factor I receptors. Evidence for a role in mitogenic signaling. J Biol Chem 1996; 271: 22506–22513.

    Article  PubMed  Google Scholar 

  70. Dong LQ, Farris S, Christal J, Liu F. Site-directed mutagenesis and yeast two-hybrid studies of the insulin and insulin-like growth factor-1 receptors: the Src homology-2 domain-containing protein hGrb 10 binds to the autophosphorylated tyrosine residues in the kinase domain of the insulin receptor. Mol Endocrinol 1997; 11: 1757–1765.

    Article  CAS  PubMed  Google Scholar 

  71. Morrione A, Valentinis B, Resnicoff M, Xu S-Q, Baserga, R. The role of mGrb1Oa in insulin-like growth factor I-mediated growth. J Biol Chem 1997; 272: 26382–26387.

    Article  CAS  PubMed  Google Scholar 

  72. Hansen H, Svensson U, Zhu J, Laviola L, Giorgino F, Wolf G, Smith RJ, Riedel H. Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus. J Biol Chem 1996; 271: 8882–8886.

    Article  CAS  PubMed  Google Scholar 

  73. Skolnik EY, Batzer A, Li N, Lee C-H, Lowenstein E, Mohammadi M, Margolis B, Schlessinger J. The function of GRB2 in linking the insulin receptor to Ras signaling pathways. Science 1993; 260: 1953 1955.

    Google Scholar 

  74. Sasaoka T, Rose DW, Juhn BH, Saltiel AR, Draznin B, Olefsky JM. Evidence for a functional role of Shc proteins in mitogenic signaling induced by insulin, insulin-like growth factor-I, and epidermal growth factor. J Biol Chem 1994; 269: 13689–13694.

    CAS  PubMed  Google Scholar 

  75. Gale NW, Kaplan S, Lowenstein EJ, Schlessinger J, Bar-Sagi D. Grb2 mediates the EGF-dependent activation of guanine nucleotide exchange on Ras. Nature (Lond) 1993; 363: 88–92.

    Article  CAS  Google Scholar 

  76. Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell 1992; 70: 431–442.

    Article  CAS  PubMed  Google Scholar 

  77. Rozakis-Adcock M, Fernley R, Wade J, Bowtell D. The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSosl. Nature 1993; 363: 83–85.

    Article  CAS  PubMed  Google Scholar 

  78. Webster J, Prager D, Melmed S. Insulin-like growth factor-I activation of extracellular signal-related kinase-1 and -2 in growth hormone-secreting cells. Mol Endocrinol 1994; 8: 539–544.

    Article  CAS  PubMed  Google Scholar 

  79. Hansson A, Thorén M. Activation of MAP kinase in Swiss 3T3 fibroblasts by insulin-like growth factor-I. Growth Regul 1995; 5: 92–100.

    CAS  PubMed  Google Scholar 

  80. Lamothe B, Bucchini D, Jami J, Joshi RL. Interaction of p85 subunit of PI 3-kinase with insulin and IGF-1 receptors analysed by using the two-hybrid system. FEBS Lett 1995; 373: 51–55.

    Article  CAS  PubMed  Google Scholar 

  81. Shemer J, Adamo MM, Wilson GL, Heffez D, Zick Y, LeRoith D. Insulin and insulin-like growth factor-I stimulate a common endogenous phosphoprotein substrate (ppl 85) in intact neuroblastoma cells. J Biol Chem 1987; 262: 15476–15482.

    CAS  PubMed  Google Scholar 

  82. Lavan BE, Lienhard GE. The insulin-elicited 60-kDa phosphotyrosine protein in rat adipocytes is associated with phosphatidylinositol 3-kinase. J Biol Chem 1993; 268: 5921–5928.

    CAS  PubMed  Google Scholar 

  83. Myers MG Jr, Sun XJ, Cheatham B, Jachna BR, Glasheen EM, Bsacker JM, White MF. IRS-1 is a common element in insulin and insulin-like growth factor-I signaling to the phosphatidylinositol 3’-kinase. Endocrinology 1993; 132: 1421–1430.

    Article  CAS  PubMed  Google Scholar 

  84. Cheatham B, Kahn CR. Insulin action and the insulin signaling network. Endocr Rev 1995; 16: 117–142.

    CAS  PubMed  Google Scholar 

  85. Sun XJ, Wang LM, Zhang Y, Yenush L, Myers MGJ, Glasheen E, Lane WS, White M. Role of IRS-2 in insulin and cytokine signaling. Nature 1995; 377: 173–177.

    Article  CAS  PubMed  Google Scholar 

  86. Lavan BE, Lane WS, Lienhard GE. The 60-kDa phosphotyrosine protein in insulin-treated adipocytes is a new member of the insulin receptor substrate family. J Biol Chem 1997; 272: 114391 1443.

    Google Scholar 

  87. Lavan BE, Fantin VR, Chang ET, Lane WS, Keller SR, Lienhard GE. A novel 160-kDa phosphotyrosine protein in insulin-treated embryonic kidney cells is a new member of the insulin receptor substrate family. J Biol Chem 1997; 272: 21403–21407.

    Article  CAS  PubMed  Google Scholar 

  88. Myers MG Jr, Backer JM, Sun X-J, Shoelson SE, Hu P, Schlessinger J, Yoakin M, Schaffhausen B, White MF. IRS-1 activates the phosphatidylinositol 3’-kinase by associating with the src homology 2 domains of p85. PNAS 1992; 89: 10350–10354.

    Article  CAS  PubMed  Google Scholar 

  89. Araki E, Lipes MA, Patti ME, Bruning JC, Haag B, Johnson RS, Kahn CR. Alternative pathway of insulin signaling in mice with targeted disruption of the IRS-1 gene. Nature 1994; 372: 186–190.

    Article  CAS  PubMed  Google Scholar 

  90. Keller S, Lienhard G. Insulin signalling: the role of insulin receptor substrate 1. Trends Cell Biol 1994; 4: 115–119.

    Article  CAS  PubMed  Google Scholar 

  91. Craparo A, O’Neill TJ, Gustafson TA. Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor. J Biol Chem 1995; 270: 15639–15643.

    Article  CAS  PubMed  Google Scholar 

  92. Kuhné MR, Pawson T, Lienhard GE, Feng G-S. The insulin receptor substrate 1 associates with the SH2-containing phosphotyrosine phosphatase Syp. J Biol Chem 1993; 268: 11479–11481.

    PubMed  Google Scholar 

  93. Pawson T, Schlessinger J. SH2 and SH3 domains. Curr Biol 1993; 3: 434–442.

    Article  CAS  PubMed  Google Scholar 

  94. Kotani K, Yonezawa K, Hara K, Ueda H, Kitamura Y, Sakaue H, Ando A, Chavanieu A, Calas B, Grigorescu F, Nishiyama M, Waterfield MD, Kasuga M. Involvement of phosphoinositide 3-kinase in insulin-or IGF-I-induced membrane ruffling. EMBO J 1994; 13: 2313–2321.

    CAS  PubMed  Google Scholar 

  95. Kooijman R, Lauf JJ, Kappers AC, Rijkers GT. Insulin-like growth factor induces phosphorylation of immunoreactive insulin receptor substrate and its association with phosphatidylinositol 3-kinase in human thymocytes. J Exp Med 1995; 182: 593–597.

    Article  CAS  PubMed  Google Scholar 

  96. Myers MG Jr, Grammer TC, Brooks J, Glasheen EM, Wang L-M, Sun XJ, Blenis J, Pierce JH, White MF. The pleckstrin homology domain in insulin receptor substrate-1 sensitizes insulin signaling. J Biol Chem 1995; 270: 11715–11718.

    Article  CAS  PubMed  Google Scholar 

  97. Voliovitch H, Schlindler DG, Hadari YR, Taylor SI, Accili D, Zick Y. Tyrosine phosphorylation of insulin receptor substrate-1 in vivo depends on the presence of its plekstrin homology region. J Biol Chem 1995; 270: 18083–18087.

    Article  CAS  PubMed  Google Scholar 

  98. Yenush L, Makati KJ, Smith-Hall J, Ishibashi O, Myers MG Jr, White MF. The pleckstrin homology domain is the principal link between the insulin receptor and IRS-1. J Biol Chem 1996; 271: 2430024306.

    Google Scholar 

  99. Tartare-Deckert S, Sawka-Verhelle D, Murdaca J, Van Obberghen E. Evidence for a differential interaction of SHC and insulin receptor substrate-1 (IRS-1) with the insulin-like growth factor-I (IGF-I) receptor in the yeast two-hybrid system. J Biol Chem 1995; 270: 23456–23460.

    Article  CAS  PubMed  Google Scholar 

  100. He W, Craparo A, Zhu Y, O’Niell TJ, Wang L-M, Pierce JH, Gustafson TA. Interaction of insulin receptor substrate-2 (IRS-2) with the insulin and insulin-like growth factor I receptors: evidence for two distinct phosphotyrosine-dependent interaction domains within IRS-2. J Biol Chem 1996; 271: 116411 1645.

    Google Scholar 

  101. Backer JM, Myers MG Jr, Shoelson SE, Chin DJ, Sun X-J, Miralpeix M, Hu P, Margolis B, Skolnik EY, Schlessinger J, White MF. Phosphatidylinositol 3’-kinase is activated by association with IRS-1 during insulin stimulation. EMBO J 1992; 11: 3469–3479.

    CAS  PubMed  Google Scholar 

  102. Giorgetti S, Ballotti R, Kowalski-Chaubel A, Tartare S, Van Obberghen E. The insulin and insulin-like growth factor-I receptor substrate IRS-1 associates with and activates phosphatidylinositol 3-kinase in vitro. J Biol Chem 1993; 268: 7358–7364.

    CAS  PubMed  Google Scholar 

  103. Nakanishi H, Brewer KA, Exton JH. Activation of the zeta isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 1993; 268: 13–16.

    CAS  PubMed  Google Scholar 

  104. Manzoli L, Billi AM, Rubbini S, Bavelloni A, Faenza I, Gilmour RS, Rhee S-G, Cocco L. Essential role for nuclear phospholipase C ßt in insulin-like growth factor I-induced mitogenesis. Cancer Res 1997; 57: 2137–2139.

    CAS  PubMed  Google Scholar 

  105. Cheatham B, Vlahos CJ, Cheatham L, Wang L, Blenis J, Kahn CR. Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol Cell Biol 1994; 14: 4902–4911.

    CAS  PubMed  Google Scholar 

  106. Chung J, Grammer TC, Lemon KP, Kazlauskas A, Blenis J. PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase. Nature 1994; 370: 71–75.

    Article  CAS  PubMed  Google Scholar 

  107. Carter AN, Downest CP. Molecular mechanisms of regulation of phosphoinositide 3-kinase by insulin, insulin-like growth factor I and nerve growth factor in PC12 cells. Biochem Soc Trans 1995; 23: 148–52.

    CAS  PubMed  Google Scholar 

  108. Matsuda M, Tanaka S, Nagata S, Kojima A, Kurata T, Shibuya M. Two species of human Crk cDNA encode proteins with distinct biological activities. Mol Cell Biol 1992; 12: 3482–3489.

    CAS  PubMed  Google Scholar 

  109. Reichman CT, Mayer BJ, Keshav S, Hanafusa H. The product of the cellular crk gene consists primarily of SH2 and SH3 regions. Cell Growth Differ 1992; 3: 451–460.

    CAS  PubMed  Google Scholar 

  110. Beitner-Johnson D, LeRoith D. Insulin-like growth factor-I stimulates tyrosine phosphorylation of endogenous c-Crk. J Biol Chem 1995; 270: 5187–5190.

    Article  CAS  PubMed  Google Scholar 

  111. Beitner-Johnson D, Blakesley VA, Shen-Orr Z, Spiegel S, LeRoith D. The proto-oncogene product c-Crk associates with insulin receptor substrate-1 and 4PS: modulation by insulin growth factor-I (IGF-I) and enhanced IGF-I signaling. J Biol Chem 1996; 271: 9287–9290.

    Article  CAS  PubMed  Google Scholar 

  112. Koval AP, Blakesley VA, Roberts CT Jr, Zick Y, LeRoith D. Direct interaction of the protein of the c-CrkII proto-oncogene with the insulin-like growth factor-I receptor. Biochem J 1998; 330: 923–932.

    CAS  PubMed  Google Scholar 

  113. Luttrell LM, van Biesen T, Hawes BE, Koch WJ, Touhara K, Lefkowitz RJ. G11 subunits mediate mitogen-activated protein kinase activation by the tyrosine kinase insulin-like growth factor-I receptor. J Biol Chem 1995; 270: 16495–16498.

    Article  CAS  PubMed  Google Scholar 

  114. Uddin S, Yetter A, Katzav S, Hoffman C, White MF, Platanias LS. Insulin-like growth factor-I induces rapid tyrosine phosphorylation of the vav proto-oncogene product. Exp Hematol 1996; 24: 622–627.

    CAS  PubMed  Google Scholar 

  115. Furlanetto RW, Day BR, Lopacznyski W, Nissley SP. 14–3–3 proteins interact with the IGF–I receptor, but not the insulin receptor. Biochem J 1997; 327: 765 – 771.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  117. Krane JF, Murphy DP, Carter DM, Krueger JG. Synergistic effects of epidermal growth factor (EGF) and insulin-like growth factor Usomatomedin C (IGF-I) on keratinocyte proliferation may be mediated by IGF-I transmodulation of the EGF receptor. J Invest Dermatol 1991; 96: 419–424.

    Article  CAS  PubMed  Google Scholar 

  118. Konstantopoulos N, Clark S. Insulin and insulin-like growth factor-1 stimulate dephosphorylation of paxillin in parallel with focal adhesion kinase. Biochem J 1996; 314: 387–390.

    CAS  PubMed  Google Scholar 

  119. Butler AA, Blakesley VA, Koval A, deJong R, Groffen J, LeRoith D. In vivo regulation of CrkII and CrkL proto-oncogenes in the uterus by insulin-like growth factor-I. Differential effects on tyrosine phosphorylation and association with paxillin. J Biol Chem 1997; 272: 27660–27664.

    Article  CAS  PubMed  Google Scholar 

  120. Ishiki M, Sasaoka T, Ishihara H, Imamura T, Usui I, Takata Y, Kobayashi M. Evidence for functional roles of Crk-II in insulin and epidermal growth factor signaling in Rat-1 fibroblasts overexpressing insulin receptors. Endocrinology 1997; 138: 4950–4958.

    Article  CAS  PubMed  Google Scholar 

  121. Foncea R, Andersson M, Ketterman A, Blakesley V, Sapag-Hagar M, Sugden PH, LeRoith D, Lavandero S. Insulin-like growth factor-I rapidly activates multiple signal transduction pathways in cultured rat cardiac myocytes. J Biol Chem 1997; 272: 19115–19124.

    Article  CAS  PubMed  Google Scholar 

  122. Neri LM, Billi AM, Manzoli L, Rubbini S, Gilmour RS, Cocco L, Martelli AM. Selective nuclear translocation of protein kinase Ca in Swiss 3T3 cells treated with IGF-I, PDGF and EGF. FEBS Lett 1994; 347: 63–68.

    Article  CAS  PubMed  Google Scholar 

  123. Oemar BS, Law NM, Rosensweig SA. Insulin-like growth factor-I induces tyrosyl phosphorylation of nuclear proteins. J Biol Chem 1991; 266: 24241–24244.

    CAS  PubMed  Google Scholar 

  124. Oppenhein RW. Cell death during development of the nervous system. Annu Rev Neurosci 1991; 14: 453–501.

    Article  Google Scholar 

  125. Galli C, Meucci O, Scorziello A, Werge TM, Calissano P, Schettini G. Apoptosis in cerebellar granule cells is blocked by high KC1 forskolin and IGF-1 through distinct mechanisms of action: the involvement of intracellular calcium and RNA synthesis. J Neurol 1995; 15: 1172–1179.

    CAS  Google Scholar 

  126. Matthews CC, Feldman EL. Insulin-like growth factor-1 rescues SH-SY5Y human neuroblastoma cells from hyperosmotic induced programmed cell death. J Cell Physiol 1996; 166: 323–331.

    Article  CAS  PubMed  Google Scholar 

  127. Johnston BM, Mallard EC, Williams CE, Gluckman PD. Insulin-like growth factor-1 is a potent neuronal rescue agent after hypoxic-ischemic injury in fetal lambs. J Clin Invest 1996; 97: 300–308.

    Article  CAS  PubMed  Google Scholar 

  128. Muta K, Krantz SB. Apoptosis of human erythroid colony-forming cells is decreased by stem cell factor and insulin-like growth factor-I as well as erythropoietin. J Cell Physiol 1993; 156: 264–271.

    Article  CAS  PubMed  Google Scholar 

  129. Jung Y-K, Miura M, Yuan J. Suppression of interleukin-1 (3-converting enzyme-mediated cell death by insulin-like growth factor. J Biol Chem 1996; 271: 5112–5117.

    Article  CAS  PubMed  Google Scholar 

  130. Harrington EA, Bennett MR, Fanidi A, Evan GI. c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines. EMBO J 1994; 13: 3286–3295.

    CAS  PubMed  Google Scholar 

  131. Chung S-Y, Billig H, Tilly JL, Furata I, Tsafriri A, Hsueh AJW. Gonadotrophin suppression of apoptosis in cultured preovulatory follicles: mediatory role of endogenous insulin-like growth factor-I. Endocrinology 1994; 135: 1845–1853.

    Article  Google Scholar 

  132. Neuenschwander S, Scwartz A, Wood TL, Roberts CT Jr, Heninghausen L, LeRoith D. Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model. J Clin Invest 1996; 97: 2225–2232.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  134. Liu J-P, Baker J, Perkins AS, Robertson EJ, Estratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor ( g f r). Cell 1993; 75: 59–72.

    CAS  PubMed  Google Scholar 

  135. Fisher DE. Apoptosis in cancer therapy: crossing the threshold. Cell 1994; 78: 539–542.

    Article  CAS  PubMed  Google Scholar 

  136. Ueda K, Ganem D. Apoptosis is induced by N-myc expression in hepatocytes, a frequent event in hepadnavirus oncogenesis, and is blocked by insulin-like growth factor II. J Virol 1996; 70: 1375–1383.

    CAS  PubMed  Google Scholar 

  137. Resnicoff M, Abraham D, Yutanawibboonchai W, Rotman HL, Kajstura J, Rubin R, Zoltick P, Baserga R. The insulin-like growth factor I receptor protects tumor cells from apoptosis in vivo. Cancer Res 1995; 55: 2463–2469.

    CAS  PubMed  Google Scholar 

  138. D’ Ambrosio C, Valentinis B, Prisco M, Reiss K, Rubini M, Baserga R. Protective effect of the insulin-like growth factor I receptor on apoptosis induced by okadaic acid. Cancer Res 1997; 57: 3264–3271.

    Google Scholar 

  139. Lee PDK, Rosenfeld RG, Hintz RL, Smith SD. Characterization of insulin, insulin-like growth factors I and II and growth hormone receptors on human leukemic lymphoblasts. J Clin Endo and Metab 1986; 62: 28–36.

    Article  CAS  Google Scholar 

  140. DeLeon DD, Bakker B, Wilson DM, Hintz RL, Rosenfeld RG. Demonstration of insulin-like growth factor (IGF-I and -II) receptors and binding protein in human breast cancer cell lines. Biochem Biophys Res Curr 1988; 152: 398–406.

    Article  CAS  Google Scholar 

  141. Macauley VM, Teale J, Everard MJ, Joshi GP, Smith IE, Millar J. Somatomedin-C insulin-like growth factor I is a mitogen for human small cell lung cancer. Br J Cancer 1988; 57: 91–98.

    Article  Google Scholar 

  142. Peyrat JP, Bonneterre J, Beuscart R, Dijane J, Demaille A. Insulin-like growth factor I receptors in human breast cancer and their relation to estradiol and progesterone receptors. Cancer Res 1988; 48: 6429–6436.

    CAS  PubMed  Google Scholar 

  143. Pollak MN, Polychronakos C, Yousefi S, Richard M. Characterization of insulin-like growth factor I (IGF-I) receptors of human breast cancer cells. BBRC 1988; 154: 326–332.

    CAS  PubMed  Google Scholar 

  144. Kurihara M, Tokunaga Y, TsuTsumi K. Characterization of insulin-like growth factor I and epidermal growth factor receptors in meningioma. J Neurosurg 1989; 71: 538–546.

    Article  CAS  PubMed  Google Scholar 

  145. Cullen KI, Yee D, Sly WS, Perdue J, Hampton B, Lippman ME, Rosen N. Insulin-like growth factor receptor expression and function in human breast cancer. Cancer Res 1990; 50: 48–53.

    CAS  PubMed  Google Scholar 

  146. Kamio T, Shigematsu K, Kawai K, Tsuchiyama H. Immunoreactivity and receptor expression of insulin-like growth factor I and insulin in human adrenal tumors. An immunohistochemical study of 94 cases. Am J Pathol 1991; 138: 83–91.

    CAS  PubMed  Google Scholar 

  147. Antoniades HN, Galanopoulos T, Neville-Golden J, Maxwell M. Expression of insulin-like growth factors I and II and their receptor mRNAs in primary human astrocytomas and meningiomas; in vivo studies using in situ hybridization and immunocytochemistry. Int J Cancer 1992; 50: 215–222.

    Article  CAS  PubMed  Google Scholar 

  148. Geier A, Beery R, Haimsohn M, Karasik A. Insulin-like growth factor-I inhibits cell death induced by anticancer drugs in the MCF-7 cells: involvement of growth factors in drug resistance. Cancer Invest 1995; 13: 480–486.

    Article  CAS  PubMed  Google Scholar 

  149. Dunn SE, Hardman RA, Kari FW, Barrett JC. Insulin-like growth factor 1 (IGF-1) alters drug sensitivity of HBL100 human breast cancer cells by inhibition of apoptosis induced by diverse anticancer drugs. Cancer Res 1997; 57: 2687–2693.

    CAS  PubMed  Google Scholar 

  150. Guvakova MA, Surmacz E. Tamoxifen interferes with the insulin-like growth factor I receptor (IGF-IR) signaling pathway in breast cancer cells. Cancer Res 1997; 57: 2606–2610.

    CAS  PubMed  Google Scholar 

  151. Parrizas M, Saltiel AR, LeRoith D. Insulin-like growth factor 1 inhibits apoptosis using the phosphatidyl 3’-kinase and mitogen-activated protein pathways. J Biol Chem 1997; 272: 154–161.

    Article  CAS  PubMed  Google Scholar 

  152. Christophori G, Naik P, Hanahan D. A second signal supplied by insulin-like growth factor II in oncogene-induced tumorigenesis. Nature 1994; 369: 414–418.

    Article  Google Scholar 

  153. Arteaga CL, Osborne CK. Growth inhibition of human breast cancer cells in vitro with an antibody against the type I somatomedin receptor. Cancer Res 1989; 49: 6237–6241.

    CAS  PubMed  Google Scholar 

  154. Kalebic T, Tsokos M, Helman LJ. In vivo treatment with antibody against IGF-1 receptor suppresses growth of human rhabdomyosarcoma and down-regulates p34cdc2 Cancer Res 1994; 54: 5531–5534.

    Google Scholar 

  155. Prager D, Li H-L, Asa S, Melmed S. Dominant negative inhibition of tumorigenesis in vivo by human insulin-like growth factor I receptor mutant. Proc Natl Acad Sci 1994; 91: 2181–2185.

    Article  CAS  PubMed  Google Scholar 

  156. Resnicoff M, Sell C, Rubini M, Coppola D, Ambrose D, Baserga R, Rubin R. Rat glioblastoma cells expressing an antisense RNA to the insulin-like growth factor-1 (IGF-1) receptor are nontumorigenic and induce regression of wild-type tumors. Cancer Res 1994; 54: 2218–2222.

    CAS  PubMed  Google Scholar 

  157. Resnicoff M, Coppola D, Sell C, Rubin R, Ferrone S, Baserga R. Growth inhibition of human melanoma cells in nude mice by antisense strategies to the type 1 insulin-like growth factor receptor. Cancer Res 1994; 54: 4848–4850.

    CAS  PubMed  Google Scholar 

  158. Sell C, Dumenil G, Deveaud C, Miura M, Coppola D, DeAngelis T, Rubin R, Efstratiadis A, Baserga R. Effect of a null mutation of the insulin-like growth factor I receptor gene on growth and transformation of mouse embryo fibroblasts. Mol Cell Biol 1994; 14: 3604–3612.

    CAS  PubMed  Google Scholar 

  159. Shapiro DN, Jones BG, Shapiro LH, Dias P, Houghton PJ. Antisense-mediated reduction in insulin-like growth factor-I receptor expression suppresses the malignant phenotype of a human alveolar rhabdomyosarcoma. J Clin Invest 1994; 94: 1235–1242.

    Article  CAS  PubMed  Google Scholar 

  160. D’ Ambrosio C, Ferber A, Resnicoff M, Baserga R. A soluble insulin-like growth factor I receptor that induces apoptosis of tumor cells in vivo and inhibits tumorigenesis. Cancer Res 1996; 56: 4013–4020.

    Google Scholar 

  161. Liu LJ, Blakesley VA, Gutkind JS, LeRoith D. The constitutively active mutant Gal 3 transforms mouse fibroblast cells deficient in insulin-like growth factor-I receptor. J Biol Chem 1997; 272: 2943829441.

    Google Scholar 

  162. O’Connor R, Kauffman-Zeh A, Liu Y, Lehar S, Evan GI, Baserga R, Blättler WA. Identification of domains of the insulin-like growth factor I receptor that are required for protection from apoptosis. Mol Cell Biol 1997; 17: 427–435.

    PubMed  Google Scholar 

  163. Wayner EA, Orlando RA, Cheresh DA. Integrins av133 and av(35 contribute to cell attachment to vitronectin but differentially distribute on the cell surface. J Cell Biol 1991; 113: 919–929.

    Article  CAS  PubMed  Google Scholar 

  164. Felding-Habermann B, Mueller BM, Romerdahl CA, Cheresh DA. Involvement of integrin av gene expression in human melanoma tumorigenicity. J Clin Invest 1992; 89: 2018–2022.

    Article  CAS  PubMed  Google Scholar 

  165. Akiyama SK, Olden K, Yamada KM. Fibronectin and integrins in invasion and metastasis. Cancer Metastas Rev 1995; 14: 173–189.

    Article  CAS  Google Scholar 

  166. Klemke RL, Yebra Y, Bayna EM, Cheresh DA. Receptor tyrosine kinase signaling is required for integrin av135-directed cell motility but not adhesion on vitronectin. J Cell Biol 1994; 127: 850–866.

    Article  Google Scholar 

  167. Rodeck U, Heryln M. Growth factors in melanoma. Cancer Metastas Rev 1991; 10: 89–101.

    Article  CAS  Google Scholar 

  168. Rodeck U, Melbor K, Kath R, Menssen H-D, Varello M, Atkinson B, Herlyn M. Constitutive expression of multiple growth factor genes by melanoma cells but not normal melanocytes. J Invest Dermatol 1991; 97: 20–26.

    Article  CAS  PubMed  Google Scholar 

  169. Matsumoto K, Ziober BL, Yao C-C, Kramer RH. Growth factor regulation of integrin-mediated cell motility. Cancer Metastas 1995; 14: 205–217.

    Article  CAS  Google Scholar 

  170. Brooks PC, Klemke RL, Schön S, Lewis JM, Schwartz MA, Cheresh DA. Insulin-like growth factor receptor cooperates with integrin aV ß5 to promote tumor cell dissemination in vivo. J Clin Invest 1997; 99: 1390–1398.

    Article  CAS  PubMed  Google Scholar 

  171. Leventhal PS, Feldman EL. Insulin-like growth factors as regulators of cell motility. Signaling mechanisms. Trends in Endosc and Metab 1997; 8: 1–6.

    Article  CAS  Google Scholar 

  172. Pfeifle B, Boeder H, Ditschuneit H. Interaction of receptors for insulin-like growth factor I, platelet-derived growth factor, and fibroblast growth factor in rat aortic cells. Endocrinology 1987; 120: 2251 2258.

    Google Scholar 

  173. Gockerman A, Prevette T, Jones JI, Clemmons DR. Insulin-like growth factor (IGF)-binding proteins inhibit the smooth muscle cell migration responses to IGF-I and IGF-II. Endocrinology 1995; 136: 41684173.

    Google Scholar 

  174. Jones JI, Prevette T, Gockerman A, Clemmons DR. Ligand occupancy of the aVI33 integrin is necessary for smooth muscle cells to migrate in response to insulin-like growth factor I. Proc Natl Acad Sci 1996; 93: 2482–2487.

    Article  CAS  PubMed  Google Scholar 

  175. Jackson CL, Reidy MA. The role of plasminogen activation in smooth muscle cell migration after arterial injury. Ann NY Acad Sci 1992; 667: 141–150.

    Article  CAS  PubMed  Google Scholar 

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Authors
  1. Vicky A. Blakesley MD, PhD
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  2. Andrew A. Butler PhD
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  3. Anatolii P. Koval PhD
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  4. Yumiko Okubo MD
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  5. Derek LeRoith MD, PhD
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Editor information

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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Blakesley, V.A., Butler, A.A., Koval, A.P., Okubo, Y., LeRoith, D. (1999). IGF-I Receptor Function. 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_7

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  • DOI: https://doi.org/10.1007/978-1-59259-712-3_7

  • Publisher Name: Humana Press, Totowa, NJ

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