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Synthesis and Characterization of IGF-II Analogs: Applications in the Evaluation of IGF Receptor Function and IGF-Independent Actions of IGFBPS

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Current Directions in Insulin-Like Growth Factor Research

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 343))

Abstract

The elucidation of the mechanisms involved in the biological actions of the IGFs has been hampered by the complexity of the IGF system: three peptide ligands (IGF-I, IGF-II and insulin),1 three receptors (type 1 and type 2 IGF receptors and insulin receptors)2 and six distinct, but structurally related binding proteins (IGFBP-1 to IGFBP-6).3 The physiological interactions among these components of the IGF system are not completely understood, although they have all been cloned and sequenced.4

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References

  1. M.M. Rechler and S.P. Nissley, Insulin-like growth factors, in: “Handbook of Experimental Pharmacology”, Vol. 95/I, “Peptide Growth Factors and Their Receptors I”, M.B. Sporn and A.B. Roberts, eds., Springer-Verlag, Berlin (1990).

    Google Scholar 

  2. Y. Oh, H.L. Müller, E.K. Neely, G. Lamson, and R.G. Rosenfeld, New concepts in insulin-like growth factor receptor physiology, Growth Regulation (in press).

    Google Scholar 

  3. R.G. Rosenfeld, G. Lamson, H. Pham, Y. Oh, C. Conover, D.D. De Leon, S.M. Donovan, I. Ocrant, and L.C. Giudice, Insulin-like growth factor binding Proteins, Rec. Prog. Horm. Res. 46:99 (1990).

    PubMed  CAS  Google Scholar 

  4. G. Steele-Perkins, J. Turner, J.C. Edman, J. Hari, S.B. Pierce, C. Stover, W.J. Rutter, and R.A. Roth, Expression and characterization of a functional human insulin-like growth factor I receptor, J. Biol. Chem. 263:11486 (1988).

    PubMed  CAS  Google Scholar 

  5. S. Shimasaki and N. Ling, Identification and molecular characterization of insulin-like growth factor binding proteins (IGFBP-1,-2,-3,-4,-5, and -6), Prog. Growth Factor Res. 3:243 (1991).

    Article  CAS  Google Scholar 

  6. D.O. Morgan, J.C. Edman, D.N. Standring, V.A. Fried, M.C. Smith, R.A. Roth, and W.J. Rutter, Insulinlike growth factor II receptor as a multifunctional binding protein, Nature 329:301 (1987).

    Article  PubMed  CAS  Google Scholar 

  7. R.G. MacDonald, S.R. Pfeffer, L. Coussens, M.A. Tepper, C.M. Brocklebank, J.E. Mole, J.K. Anderson, E. Chen, M.P. Czech, and A. Ullrich, A single receptor binds both insulin-like growth factor-II and mannose-6-phosphate, Science 239:1134 (1988).

    Article  PubMed  CAS  Google Scholar 

  8. P.Y. Tong, S.E. Tollefsen, and S. Kornfeld, The cation-independent mannose-6-phosphate receptor binds insulin-like growth factor II, J. Biol. Chem. 263:2585 (1988).

    PubMed  CAS  Google Scholar 

  9. Y. Oh, H.L. Müller, H. Pham, G. Lamson, and R.G. Rosenfeld, Non-receptor mediated, post-transcriptional regulation of insulin-like growth factor binding protein-3 in Hs578T human breast cancer cells, Endocrinology 131:3123 (1992).

    Article  PubMed  CAS  Google Scholar 

  10. C. Camacho-Hubner, W.H.Jr. Busby, R.H. McCusker, G. Wright, and D.R. Clemmons, Identification of the forms of insulin-like growth factor-binding proteins produced by human fibroblasts and the mechanisms that regulate their secretion, J. Biol. Chem. 267:11949 (1992).

    PubMed  CAS  Google Scholar 

  11. C.A. Conover, P. Misra, R.L. Hintz, and R.G. Rosenfeld, Effect of an anti-insulin-like growth factor I receptor antibody on insulin-like growth factor II stimulation of DNA synthesis in human fibroblasts, Biochem. Biophys. Res. Commun. 139:501 (1987).

    Article  Google Scholar 

  12. J. Hari, S.B. Pierce, D.O. Morgan, V. Sara, M.C. Smith, and R.A. Roth, The receptor for insulin-like growth factor II mediates an insulin-like response, EMBO J. 6:3367 (1987).

    PubMed  CAS  Google Scholar 

  13. I. Kojima, I. Nishimoto, T. Iiri, E. Ogata, and R.G. Rosenfeld, Evidence that type II insulin-like growth factor receptor is coupled to calcium gating system, Biochem. Biophys. Res. Commun. 154:9 (1988).

    Article  PubMed  CAS  Google Scholar 

  14. C. Mottola and M.P. Czech, The type II insulin-like growth factor receptor does not mediate increased DNA synthesis in H-35 hepatoma cells, J. Biol. Chem. 259:12705 (1984).

    PubMed  CAS  Google Scholar 

  15. E.Y. Adashi, C.E. Resnick, and R.G. Rosenfeld, Insulin-like growth factor -I (IGF-I) hormonal action in cultured rat granulosa cells: Mediation via type I but not type II IGF receptors, Endocrinology 126:216 (1989).

    Article  Google Scholar 

  16. G. Steele-Perkins and R.A. Roth, Monoclonal antibody alphaIR3 inhibits the ability of insulin-like growth factor II to stimulate a signal from the type-I receptor without inhibiting its binding, Biochem. Biophys. Res. Commun. 171:1244 (1990).

    Article  PubMed  CAS  Google Scholar 

  17. G. Steele-Perkins and R.A. Roth, Insulin-mimetic anti-insulin receptor monoclonal antibodies stimulate receptor kinase activity in intact cells, J. Biol. Chem. 265:9458 (1990).

    PubMed  CAS  Google Scholar 

  18. T.L. Blundell, S. Berdarka, E. Rinderknecht, and R.E. Humbel, Insulin-like growth factor: A model for tertiary structure accounting for immunoreactivity and receptor binding, Biochemistry 75:180 (1978).

    CAS  Google Scholar 

  19. M.A. Cascieri and M.L. Bayne, Identification of the domains of IGF-I which interact with the IGF receptors and binding proteins, in: “Molecular and Cellular Biology of Insulin-like Growth Factors and Their Receptor”, D. ReRoith and M.K. Raizada, eds., Plenum Press, NY (1989).

    Google Scholar 

  20. M.L. Bayne, J. Applebaum, G.G. Chicchi, N.S. Hayes, B.G. Green, and M.A. Cascieri, Structural analogs of human insulin-like growth factor I with reduced affinity for serum binding proteins and the type 2 insulin-like growth factor receptor, J. Biol. Chem. 263:6233 (1988).

    PubMed  CAS  Google Scholar 

  21. M.A. Cascieri, G.G. Chicchi, J. Applebaum, B.G. Green, N.S. Hayes, and M.L. Bayne, Structural analogs of human insulin-like growth factor (IGF) I with altered affinity for type 2 IGF receptors J. Biol. Chem. 264:2199 (1989).

    PubMed  CAS  Google Scholar 

  22. ML. Bayne, J. Applebaum, G.G. Chicchi, R.E. Miller, and M.A. Cascieri, The role of tyrosines 24, 31, and 60 in the high affinity binding of insulin-like growth factor-I to the type 1 insulin-like growth factor receptor, J. Biol. Chem. 265:15648 (1990).

    PubMed  CAS  Google Scholar 

  23. N. Ling, F. Esch, P. Böhlen, P. Brazeau, W.B. Wehrenberg, and R. Guillemin, Isolation, primary structure and synthesis of human hypothalamic somatocrinin: Growth hormone-releasing factor, Proc. Nat. Acad. Sci. USA. 81:4302 (1984).

    Article  PubMed  CAS  Google Scholar 

  24. J.P. Tam, W.F. Heath, and R.B. Merrifield, SN2 deprotection of synthetic peptides with a low concentration of HF in dimethylsulfide: Evidence and application in peptide synthesis, J. Am. Chem. Soc. 105:6442 (1983).

    Article  CAS  Google Scholar 

  25. M.W. Beukers, Y. Oh, H. Zhang, N. Ling, and R.G. Rosenfeld, [Leu27]insulin-like growth factor II is highly selective for the type-II IGF receptor in binding, cross-linking and thymidine incorporation experiments, Endocrinology 128:1201 (1991).

    CAS  Google Scholar 

  26. Y. Oh, H.L. Müller, D. Lee, P. J. Fielder, and R.G. Rosenfeld, Characterization of the affinities of insulinlike growth factor (IGF)-binding proteins 1-4 for IGF-I, IGF-II, IGF/insulin hybrid, and IGF-I analogs, Endocrinology 132:1337 (1993).

    Article  PubMed  CAS  Google Scholar 

  27. M.C. Kiefer, C.S. Schmid, M. Waldvogel, I.Schläpfer, E. Futo, F.R. Masiarz, K. Green, P.J. Barr, and J. Zapf, Characterization of recombinant human insulin-like growth factor binding proteins 4, 5, and 6 produced in Yeast, J. Biol. Chem. 267:12692 (1992).

    PubMed  CAS  Google Scholar 

  28. Y. Oh, M.W. Beukers, H. Pham, P.A. Smanik, M.C. Smith, and R.G. Rosenfeld, Altered affinity of insulin-like growth factor II (IGF-II) for receptors and IGF-binding proteins, resulting from limited modifications of the IGF-II molecule, Biochem. J. 278:249 (1991).

    PubMed  CAS  Google Scholar 

  29. D.M. Bürgisser, B.V. Rith, R. Giger, C. Lüthi, S. Weigl, J. Zarn, and R.E. Humbel, Mutants of human insulin-like growth factor II with altered affinities for the type 1 and type 2 insulin-like growth factor receptor, J. Biol. Chem. 266:1029 (1991).

    PubMed  Google Scholar 

  30. K. Sakano, T. Enjoh, F. Numata, H. Fujiwara, Y. Marumoto, N. Higashihashi, Y. Sato, J.F. Perdue, and Y.F. Yamaguchi, The design, expression, and characterization of human insulin-like growth factor II (IGF-II) mutants specific for either the IGF-II/cation-independent mannose 6-phosphate receptor or IGF-I receptor, J. Biol. Chem. 266:20626 (1991).

    PubMed  CAS  Google Scholar 

  31. W. Kiess, G.D. Blickenstaff, M.M. Sklar, C.L. Thomas, S.P. Nissley, and G.C. Sahagian, Biochemical evidence that type II insulin-like growth factor receptor is identical to the cation-independent mannose 6-phosphate receptor, J. Biol. Chem. 263:9339 (1988).

    PubMed  CAS  Google Scholar 

  32. W. Kiess, C.L. Thomas, M.M. Sklar, and S.P. Nissley, ß-galactosidase decreases the binding affinity of the insulin-like growth factor II/mannose 6-phosphate receptor for insulin-like growth factor II, Eur. J. Biochem. 190:71 (1990).

    Article  PubMed  CAS  Google Scholar 

  33. I. Nishimoto, Y. Hata, E. Ogata, and I, Kojima, Insulin-like growth factor II stimulates calcium influx in competent Balb/c 3T3 cells primed with epidermal growth factor: Characteristics of calcium influx and involvement of GTP-binding protein, J. Biol. Chem. 262:12120 (1987).

    PubMed  CAS  Google Scholar 

  34. T. Okamoto, T. Katada, Y. Murayama, M Ui, E. Ogata, and I. Nishimoto, A simple structure encodes G protein-activating function of the IGF-II/mannose 6-phosphate receptor, Cell 62:709 (1990).

    Article  PubMed  CAS  Google Scholar 

  35. O.M. El-Badry, C.P. Minniti, E.C. Kohn, P.J. Houghton, W.H. Daughaday, and L.J. Helman, Insulin-like growth factor II acts as an autocrine growth and motility factor in human rhabdomyosarcoma tumors, Cell Growth &Differ. 1:325 (1990).

    CAS  Google Scholar 

  36. C.P. Minniti, E.C. Kohn, J.H. Grubb, W.S. Sly, Y. Oh, H.L. Müller, R.G. Rosenfeld, and L.J. Helman, The insulin-like growth factor II (IGF-II)/mannose 6-phosphate receptor mediates IGF-II-induced motility in human rhabdomyosarcoma cells, J. Biol. Chem. 267:9000 (1992).

    PubMed  CAS  Google Scholar 

  37. J. Delbé, C. Blat, G. Desauty, and L. Harel, Presence of IDF45 (mIGFBP-3) binding sites on chick embryo fibroblasts, Biochem. Biophys. Res. Commun. 179:495 (1991).

    Article  PubMed  Google Scholar 

  38. J.L. Martin, M. Ballesteros, and R.C. Baxter, Insulin-like growth factor-I (IGF-I) and transforming growth factor-ß1 release IGF-binding protein-3 from human fibroblasts by different mechanisms, Endocrinology131:1703 (1992).

    Article  PubMed  CAS  Google Scholar 

  39. Y. Oh, H.L. Müller, H. Pham, G. Lamson, and R.G. Rosenfeld, Insulin-like growth factor binding protein (IGFBP)-3 levels in conditioned media of Hs578T human breast cancer cells are post-transcriptionally regulated, Growth Regulation 3:84 (1993).

    PubMed  CAS  Google Scholar 

  40. Y. Oh, H.L. Müller, G. Lamson, and R.G. Rosenfeld, Insulin-like growth factor (IGF)-independent action of IGF binding protein (BP)-3 in Hs578T human breast cancer cells: cell surface binding and growth inhibition, J. Biol. Chem. (in press).

    Google Scholar 

  41. D.D. DeLeon, D.M. Wilson, M. Powers, and R.G. Rosenfeld, Effects of insulin-like growth factors (IGFs) and IGF receptor antibodies on the proliferation of human breast cancer cells, Growth Factors 6:327 (1992).

    Article  CAS  Google Scholar 

  42. B.W. Ennis, E.M. Valverius, S.E. Bates, M.E. Lippman, F. Bellot, R. Kris, J. Schlessinger, H. Masui, A. Goldenberg, J. Mendelsohn, and R.B. Dickson, Anti-epidermal growth factor receptor antibodies inhibit the autocrine-stimulated growth of MDA-468 human breast cancer cells, Mol. Endocrinol 3:1830 (1989).

    Article  PubMed  CAS  Google Scholar 

  43. M.H. Kraus, Y. Yuasa, and S.A. Aaronson, A position 12-activated H-ras oncogene in all Hs578T mammary carcinosarcoma cells but not normal mammary cells of the same patient, Biochemistry 81:5384(1984).

    CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Dept. of Pediatrics, Div. of Endocrinology, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Youngman Oh, Hermann L. Müller & Ron G. Rosenfeld

  2. Dept. of Molecular Endocrinology, The Whittier Institute for Diabetes and Endocrinology, La Jolla, CA, 92037, USA

    Heping Zhang & Nicholas Ling

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  1. Youngman Oh
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  2. Hermann L. Müller
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  3. Heping Zhang
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  4. Nicholas Ling
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  5. Ron G. Rosenfeld
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Editor information

Editors and Affiliations

  1. National Institutes of Health, Bethesda, Maryland, USA

    Derek Le Roith M.D., Ph.D.

  2. University of Florida, Gainesville, Florida, USA

    Mohan K. Raizada Ph.D.

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Oh, Y., Müller, H.L., Zhang, H., Ling, N., Rosenfeld, R.G. (1994). Synthesis and Characterization of IGF-II Analogs: Applications in the Evaluation of IGF Receptor Function and IGF-Independent Actions of IGFBPS. In: Le Roith, D., Raizada, M.K. (eds) Current Directions in Insulin-Like Growth Factor Research. Advances in Experimental Medicine and Biology, vol 343. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2988-0_5

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  • DOI: https://doi.org/10.1007/978-1-4615-2988-0_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6301-9

  • Online ISBN: 978-1-4615-2988-0

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