Characterization and Cloning of a Rat Insulin-Like Growth Factor Binding Protein

  • Matthew M. Rechler
  • Alexandra L. Brown
  • Craig C. Orlowski
  • Yvonne W.-H. Yang
  • Joyce A. Romanus
  • Lorenzo Chiariotti
  • Carmelo B. Bruni


The insulin-like growth factors, IGF-I and IGF-II, occur complexed to specific binding proteins in blood and other extracellular fluids.1 IGF-binding protein complexes of 150 kDa predominate in adult human and rat serum2,3, and also have been observed in human and porcine milk 4,5, and human fibroblast conditioned media6,7. Acid pH irreversibly dissociates the 150 kDa binding protein complex into an ~40 kDa acid-stable binding subunit.1 Recently, Baxter8 provided evidence for the existence of a second subunit of ~100 kDa that is unstable at acid pH and does not bind IGFs.


Human Amniotic Fluid Human Cerebrospinal Fluid Ligand Blotting Carboxyl Terminal Region Porcine Milk 
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  1. 1.
    Nissley, S.P. and Rechler, M.M. Insulin-like growth factors: biosynthesis, receptors, and carrier proteins, in: “Hormonal Proteins and Peptides”, Vol. XII, C.H. Li, ed., Academic Press, New York and London (1984).Google Scholar
  2. 2.
    R.M. White, S.P. Nissley, A.C. Moses, M.M. Rechler, and R.E. Johnsonbaugh, The growth hormone dependence of a somatomedin-binding protein in human serum, J. Clin. Endocrinol. Metab. 53:49 (1981).PubMedCrossRefGoogle Scholar
  3. 3.
    A.C. Moses, S.P. Nissley, K.L. Cohen, and M.M. Rechler, Specific binding of a somatomedin-like polypeptide in rat serum depends on growth hormone, Nature 263:137 (1976).PubMedCrossRefGoogle Scholar
  4. 4.
    R.C. Baxter, Z. Zaltsman, and J.R. Turtle, Immunoreactive somatomedin-C/insulin-like growth factor I and its binding protein in human milk, J.Clin.Endocrinol.Metab. 58:955 (1984).PubMedCrossRefGoogle Scholar
  5. 5.
    F.A. Simmen, R.C.M. Simmen, and G. Reinhart, Maternal and neonatal somatomedin C/insulin-like growth factor I (IGF-I) during early lactation in the pig, Dev. Biol. 130:16 (1988).PubMedCrossRefGoogle Scholar
  6. 6.
    D.R. Clemmons, L.E. Underwood, and J.J. Van Wyk, Hormonal control of immunoreactive somatomedin production by cultured human fibroblasts, J. Clin. Invest. 67:10 (1981).PubMedCrossRefGoogle Scholar
  7. 7.
    J.S.M. De Mellow, and R.C. Baxter, Growth hormone-dependent insulin-like growth factor (IGF) binding protein both inhibits and potentiates IGF-I-stimulated DNA synthesis in human skin fibroblasts, Biochem. Biophys. Res. Commun. 156:199 (1988).PubMedCrossRefGoogle Scholar
  8. 8.
    R.C. Baxter, Characterization of the acid-labile subunit of the growth hormone-dependent insulin-like growth factor binding protein complex, J. Clin. Endocrinol. Metab. 67:265 (1988).PubMedCrossRefGoogle Scholar
  9. 9.
    R.C. Baxter, J.L. Martin, and M.H. Wood, Two immunoreactive binding proteins for insulin-like growth factors in human amniotic fluid: relationship to fetal maturity, J.Clin.Endocrinol.Metab. 65:423 (1987).PubMedCrossRefGoogle Scholar
  10. 10.
    P. Hossenlopp, D. Seurin, B. Segovia-Quinson, and M. Binoux, Identification of an insulin-like growth factor-binding protein in human cerebrospinal fluid with a selective affinity for IGF-II, FEBS Lett. 208:439 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    J.L. Martin, and R.C. Baxter, Insulin-like growth factor-binding protein from human plasma: Purification and characterization, J.Biol.Chem. 261:8754 (1986).PubMedGoogle Scholar
  12. 12.
    G.R. Elgin, W.H.Jr. Busby, and D.R. Clemmons, An insulin-like growth factor (IGF) binding protein enhances the biologic response to IGF I, Proc.Natl.Acad.Sci.U.S.A. 84:3254 (1987).PubMedCrossRefGoogle Scholar
  13. 13.
    S. Hardouin, P. Hossenlopp, B. Segovia, D. Seurin, G. Portolan, C. Lassarre, and M. Binoux, Heterogeneity of insulin-like growth factor binding proteins and relationships between structure and affinity: 1. circulating forms in man, Eur. J. Biochem. 170:121 (1987).PubMedCrossRefGoogle Scholar
  14. 14.
    Y.W-H. Yang, J-F. Wang, J.A. Romanus, and M.M. Rechler, manuscript in preparation.Google Scholar
  15. 15.
    J. Zapf, W. Born, J-Y. Chang, P. James, E.R. Froesch, and J.A. Fischer, Isolation and NH2-terminal amino acid sequences of rat serum carrier proteins for insulin-like growth factors. Biochem. Biophys. Res. Commun. 156:1187 (1988).PubMedCrossRefGoogle Scholar
  16. 16.
    J.A. Romanus, J.E. Terrell, Y.W. Yang, S.P. Nissley, and M.M. Rechler, Insulin-like growth factor carrier proteins in neonatal and adult rat serum are immunologically different: demonstration using a new radioimmunoassay for the carrier protein from BRL-3A rat liver cells. Endocrinology 118:1743 (1986).PubMedCrossRefGoogle Scholar
  17. 17.
    R.M. Lyons, and G.L. Smith, Characterization of multiplication-stimulating activity (MSA) carrier protein, Mol. Cell. Endocrinol. 45:263 (1986).PubMedCrossRefGoogle Scholar
  18. 18.
    C. Mottola, R.G. MacDonald, J.L. Bracken, J.E. Mole, J.K. Anderson, and M.P. Czech, Purification and amino-terminal sequence of an insulin-like growth factor-binding protein secreted by rat liver BRL-3A cells, J. Biol. Chem. 261:11180 (1986).PubMedGoogle Scholar
  19. 19.
    J.A. Romanus, Y.W-H. Yang, S.P. Nissley, and M.M. Rechler, Biosynthesis of the low molecular weight carrier protein for insulin-like growth factors in rat liver and fibroblasts, Endocrinology 121:1041 (1987).PubMedCrossRefGoogle Scholar
  20. 20.
    J-F. Wang, B. Hampton, T. Mehlman, W.H. Burgess, and M.M. Rechler, Isolation of a biologically active fragment from the carboxy-terminus of the fetal rat binding protein for insulin-like growth factors, Biochem. Biophys. Res. Commun. 157:718 (1988).PubMedCrossRefGoogle Scholar
  21. 21.
    A.L. Brown, D.E. Graham, S.P. Nissley, D.J. Hill, A.J. Strain, and M.M. Rechler, Developmental regulation of insulin-like growth factor II mRNA in different rat tissues, J.Biol.Chem. 261:13144 (1986).PubMedGoogle Scholar
  22. 22.
    A.L. Brown, L. Chiariotti, C. Orlowski, T. Mehlman, W.H. Burgess, E.J. Ackerman, C.B. Bruni, and M.M. Rechler, Nucleotide sequence and expression of a cDNA clone encoding a fetal rat binding protein for insulin-like growth factors, J. Biol. Chem. (1989). (In Press)Google Scholar
  23. 23.
    E. Ruoslahti, and M.D. Pierschbacher, New perspectives in cell adhesion: RGD and integrins, Science 238:491 (1987).PubMedCrossRefGoogle Scholar
  24. 24.
    A. Ullrich, A. Gray, A.W. Tam, T. Yang-Feng, M. Tsubokawa, C. Collins, W. Henzel, T. Le Bon, S. Kathuria, E. Chen, S. Jacobs, U. Francke, J. Ramachandran, and Y. Fujita-Yamaguchi, Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity, EMBO J. 5:2503 (1986).PubMedGoogle Scholar
  25. 25.
    D.O. Morgan, J.C. Edman, D.N. Standring, V.A. Fried, M.C. Smith, R.A. Roth, and W.J. Rutter, Insulin-like growth factor II receptor as a multifunctional binding protein, Nature 329:301 (1987).PubMedCrossRefGoogle Scholar
  26. 26.
    W.I. Wood, G. Cachianes, W.J. Henzel, G.A. Winslow, S.A. Spencer, R. Hellmiss, J.L. Martin, and R.C. Baxter, Cloning and expression of the growth hormone-dependent insulin-like growth factor binding protein, Mol. Endocrinol. 2:1176.Google Scholar
  27. 27.
    M.T. Brewer, G.L. Stetler, C.H. Squires, R.C. Thompson, W.H. Busby, and D.R. Clemmons, Cloning, characterization, and expression of a human insulin-like growth factor binding protein, Biochem. Biophvs. Res. Commun. 152:1289 (1988).CrossRefGoogle Scholar
  28. 28.
    A. Brinkman, C. Groffen, D.J. Kortleve, A.G. van Kessel, and S.L.S. Drop, Isolation and characterization of a cDNA encoding the low molecular weight insulin-like growth factor binding protein (IBP-1), EMBO J. 7:2417 (1988).PubMedGoogle Scholar
  29. 29.
    M. Julkunen, R. Koistinen, K. Aalto-Setala, M. Seppala, O.A. Janne, and K. Kontula, Primary structure of human insulin-like growth factor-binding protein/placental protein 12 and tissue-specific expression of its mRNA, FEBS Lett. 236:295 (1988).PubMedCrossRefGoogle Scholar
  30. 30.
    Y-L. Lee, R.L. Hintz, P.M. James, P.D.K. Lee, J.E. Shively, and D.R. Powell, Insulinlike growth factor (IGF) binding protein complementary deoxyribonucleic acid from human HEP G2 hepatoma cells: predicted protein sequence suggests an IGF binding domain different from those of the IGF-I and IGF-II receptors, Mol. Endocrinol. 2:404 (1988).PubMedCrossRefGoogle Scholar
  31. 31.
    L. Szabo, D.G. Mottershead, F.J. Ballard, and J.C. Wallace, The bovine insulin-like growth factor (IGF) binding protein purified from conditioned medium requires the N-terminal tripeptide in IGF-1 for binding, Biochem. Biophys. Res. Commun. 151:207 (1988).CrossRefGoogle Scholar
  32. 32.
    C.C. Orlowski, L.Y-H. Tseng, A.L. Brown, T. Taylor, Y.W-H. Yang, J.A. Romanus, and M.M. Rechler, Insulin-like growth factor II (IGF-II) and the BRL-3A IGF binding protein are expressed coordinately in adult rat choroid plexus and cerebrospinal fluid, Program of the Endocrine Society (1989).Google Scholar
  33. 33.
    L.Y-H. Tseng, A.L. Brown, T. Taylor, Y.W-H. Yang, J.A. Romanus, and M.M. Rechler, manuscript in preparation.Google Scholar
  34. 34.
    F. Stylianopoulou, J. Herbert, M.B. Soares, and A. Efstratiadis, Expression of the insulin-like growth factor II gene in the choroid plexus and the leptomeninges of the adult rat central nervous system, Proc. Natl. Acad. Sci. USA 85:141 (1988).PubMedCrossRefGoogle Scholar
  35. 35.
    M.A. Hynes, P.J. Brooks, J.J. Van Wyk, and P.K. Lund, Insulin-like growth factor II messenger ribonucleic acids are synthesized in the choroid plexus of the rat brain, Mol. Endocrinol. 1:47 (1988).Google Scholar
  36. 36.
    M. Binoux, C. Lassarre, and M. Gourmelen, Specific assay for insulin-like growth factor (IGF-II) using the IGF binding proteins extracted from human cerebrospinal fluid, J. Clin. Endocrinol. Metab. 63:1151 (1986).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Matthew M. Rechler
    • 1
  • Alexandra L. Brown
    • 1
  • Craig C. Orlowski
    • 1
  • Yvonne W.-H. Yang
    • 1
  • Joyce A. Romanus
    • 1
  • Lorenzo Chiariotti
    • 2
  • Carmelo B. Bruni
    • 2
  1. 1.Molecular, Cellular and Nutritional Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaUSA
  2. 2.Centro di Endocrinologica ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e MolecolareUniversita degli Studi di NapoliItaly

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