Advertisement

The Structure and Expression of the Human Insulin-Like Growth Factor Genes

  • Pieternella Holthuizen

Abstract

The insulin-like growth factors (IGF) are a group of peptides involved in mammalian growth and development (37). The complete structures of two major species were first elucidated by Rinderknecht and Humbel (27,28). IGF-I is a basic peptide of 70 amino acids which mediates the growth promoting action of growth hormone and plays an important role in postnatal growth. The biological action of IGF-II, a 67 amino acids long peptide, is less obvious. It is thought to stimulate a variety of growth promoting processes in the fetus but several studies also indicate a function for IGF-II in the postnatal stage (4).

Keywords

Adult Liver cDNA Library 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bell GI, Merryweather JP, Sanchez-Pescador R, Stempien MM, Priestley L, Scott J, Rall LB (1984) Sequence of a cDNA clone encoding human preproinsulin-like growth factor II. Nature 310:775–777PubMedCrossRefGoogle Scholar
  2. 2.
    Bell GI, Gerhard DS, Fong NM, Sanchez-Pescador R, Rall LB (1985) Isolation of the insulin-like growth factor genes: Insulin-like growth factor II and insulin genes are contiguous. Proc Natl Acad Sci USA 82:6450–6454PubMedCrossRefGoogle Scholar
  3. 3.
    Brissenden JE, Ullrich A, Francke U (1984) Human chromosomal mapping of genes for insulin-like growth factors I and II and epidermal growth factor. Nature 310:781–784PubMedCrossRefGoogle Scholar
  4. 4.
    D’Ercole AJ, Stiles AD, Underwood LE (1984) Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci USA 81:935–939PubMedCrossRefGoogle Scholar
  5. 5.
    De Pagter-Holthuizen P, Höppener JWM, Jansen M, Geurts van Kessel AHM, Van Ommen GJB, Sussenbach JS (1985) Chromosomal localization and preliminary characterization of the human gene encoding insulin-like growth factor II. Hum Genet 69:170–173PubMedCrossRefGoogle Scholar
  6. 6.
    De Pagter-Holthuizen P, Van Schaik FMA, Verduijn GM, Van Ommen GJB, Bouma BN, Jansen M, Sussenbach JS (1986) Organization of the human genes for insulin-like growth factors I and II. FEBS Lett 195:179–184PubMedCrossRefGoogle Scholar
  7. 7.
    De Pagter-Holthuizen P, Jansen M, Van Schaik FMA, van der Kammen RA, Oosterwijk C, Van den Brande JL, Sussenbach JS (1987) The human insulin-like growth factor II contains two development-specific promoters. FEBS Lett 214:259–264PubMedCrossRefGoogle Scholar
  8. 8.
    De Pagter-Holthuizen P, Jansen M, van der Kammen RA, Van Schaik FMA, Sussenbach JS (1988) Differential expression of the human insulin-like growth factor II gene. Characterization of the IGF-II mRNAs and an mRNA encoding a putative IGF-II-associated protein. Biochim Biophys Acta 950:282–295PubMedGoogle Scholar
  9. 9.
    Dull TJ, Gray A, Hayflick JS, Ullrich A (1984) Insulin-like growth factor II precursor gene organization in relation to the insulin gene family. Nature 310:777–781PubMedCrossRefGoogle Scholar
  10. 10.
    Han VKM, D’Ercole AJ, Lund PK (1987) Cellular localization of somatomedin (insulin-like growth factor) messenger RNA in the human fetus. Science 236:193–197PubMedCrossRefGoogle Scholar
  11. 11.
    Han VKM, Hill DJ, Strain AJ, Towle AC, Lauder JM, Underwood LE, D’Ercole AJ (1987) Identification of somatomedin/insulin-like growth factor immunoreactive cells in the human fetus. Pediatric Res 22:245–249CrossRefGoogle Scholar
  12. 12.
    Han VKM, Lund PK, Lee DC, D’Ercole AJ (1988) Expression of somatomedin/insulin-like growth factor messenger ribonucleic acids in the human fetus: Identification, characterization and tissue distribution. J Clin Endocrinol Metabol 66:422–429CrossRefGoogle Scholar
  13. 13.
    Haselbacher GK, Irminger JC, Zapf J, Ziegler WH, Humbel RE (1987) Insulin-like growth factor II in human adrenal pheochromocytomas and Wilms tumors: expression at the mRNA and protein level. Proc Natl Acad Sci USA 84:1104–1106PubMedCrossRefGoogle Scholar
  14. 14.
    Huff KK, Kaufman D, Gabbay KH, Spencer EM, Lippman ME, Dickson RB (1986) Secretion of an insulin-like growth factor-I-related protein by human breast cancer cells. Cancer Res 46:4631–4619Google Scholar
  15. 15.
    Höppener JWM, De Pagter-Holthuizen P, Geurts van Kessel AHM, Jansen M, Kittur SD, Antonorakis SE, Lips CJM, Sussenbach JS (1985) The human gene encoding insulin-like growth factor I is located on chromosome 12. Hum Genet 69:157–160PubMedCrossRefGoogle Scholar
  16. 16.
    Höppener JWM, Steenbergh PH, Slebos RJC, De Pagter-Holthuizen P, Jansen M, Roos BA, Van den Brande JL, Sussenbach JS, Jansz HS, Lips CJM (1987) Expression of insulin-like growth factor -I and -II genes in rat medullary thyroid carcinoma. FEBS Lett 215:122–126PubMedCrossRefGoogle Scholar
  17. 17.
    Höppener JWM, Mosselman S, Roholl PJM, Lambrechts, Slebos RJC, De Pagter-Holthuizen P, Lips CJM, Jansz HS, Sussenbach JS (1988) Expression of insulin-like growth factor-I and -II genes in human smooth muscle tumours. EMBO J 7:1379–1385PubMedGoogle Scholar
  18. 18.
    Irminger JC, Rosen KM, Humbel RE, Vila-Komaroff L (1987) Tissue-specific expression of insulin-like growth factor II mRNAs with distinct 5′ untranslated regions. Biochemistry 84:6330–6334Google Scholar
  19. 19.
    Jansen M, Van Schaik FMA, Ricker AT, Bullock B, Woods KH, Gabbay DE, Nussbaum AL, Sussenbach JS, Van den Brande JL (1983) Sequence of cDNA encoding human insulin-like growth factor I precursor. Nature 306:609–611PubMedCrossRefGoogle Scholar
  20. 20.
    Jansen M, Van Schaik FMA, Van Tol H, Van den Brande JL,, Sussenbach JS (1985) Nucleotide sequences of cDNAs encoding precursors of human insulin-like growth factor II (IGF-II) and an IGF-II variant. FEBS Lett 179:243–246PubMedCrossRefGoogle Scholar
  21. 21.
    Jansen M, De Pagter-Holthuizen P, Höppener JWM, Sussenbach JS, Van den Brande JL (1987) Somatomedin gene structure and expression. In: Highlights on endocrinology. Eds. C. Christiansen, BJ Riis, Kopenhagen.Google Scholar
  22. 22.
    Knowles BB, Howe CC, Aden DP (1980) Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 209:497–499PubMedCrossRefGoogle Scholar
  23. 23.
    Kozak M (1987) An analysis of 5′ noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res 15:8125–8132PubMedCrossRefGoogle Scholar
  24. 24.
    LeBouc Y, Dreyer D, Jaeger F, Binoux M, Sondermeyer P (1986) Complete characterization of the human IGF-I nucleotide sequence isolated from a newly constructed adult liver cDNA library. FEBS Lett 196:108–112CrossRefGoogle Scholar
  25. 25.
    LeBouc Y, Noguiez P, Sondermeyer P, Dreyer D, Girard F, Binoux M (1987) A new 5′-non-coding region for human placental insulin-like growth factor II mRNA expression. FEBS Lett 222:181–185CrossRefGoogle Scholar
  26. 26.
    Mannens M, Slater RM, Heyting C, Bliek J, De Kraker J, Coad N, De Pagter-Holthuizen P, Pearson PL (1988) Molecular nature of genetic changes resulting in loss of heterozygosity of chromosome 11 in Wilms’ tumours. Hum Genet 81:41–48PubMedCrossRefGoogle Scholar
  27. 27.
    Rinderknecht E, Humbel RE (1978a) The amino-acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem 253:2769–2775PubMedGoogle Scholar
  28. 28.
    Rinderknecht E, Humbel RE (1978b) Primary structure of human insulin-like growth factor II. FEBS Lett 89:283–286PubMedCrossRefGoogle Scholar
  29. 29.
    Rotwein P (1986) Two insulin-like growth factor I messenger RNAs are expressed in human liver. Proc Natl Acad Sci USA 83:77–81PubMedCrossRefGoogle Scholar
  30. 30.
    Rotwein P, Folz RJ, Gordon JI (1987) Biosynthesis of human insulin-like growth factor I. The primary translation product of IGF-I mRNA contains an unusual 48 amino acid signal peptide. J Biol Chem 262:11807–11812PubMedGoogle Scholar
  31. 31.
    Rotwein P, Pollock KM, Didier DK, Krivi GG (1986) Organization and sequence of the human insulin-like growth factor I gene. J Biol Chem 261:4828–4832PubMedGoogle Scholar
  32. 32.
    Schofield PN, Tate VE (1989) Development regulation of IGF-II transcription. In press.Google Scholar
  33. 33.
    Shen SJ, Daimon M, Wang CY, Jansen M, Han J (1986) Isolation of an insulin-like growth factor II cDNA with a unique 5′ untranslated region from human placenta. Proc Natl Acad Sci USA 85:1947–1951CrossRefGoogle Scholar
  34. 34.
    Sussenbach JS (1989) The gene structure of the insulin-like growth factor family. Progress Growth Factor Res 1:33–48CrossRefGoogle Scholar
  35. 35.
    Tricoli JV, Rall LB, Scott J, Bell GI, Shows TB (1984) Localization of insulin-like growth factor genes to human chromosomes 11 and 12. Nature 310:784–786PubMedCrossRefGoogle Scholar
  36. 36.
    Ullrich A, Berman CH, Dull TJ, Gray A, Lee JM (1984) Isolation of the human insulin-like growth factor I gene using a synthetic DNA probe. EMBO J 3:361–364PubMedGoogle Scholar
  37. 37.
    Zapf J, Schmid C, Froesch ER (1984) Biological and immunological properties of insulin-like growth factors I and II. Clin Endocrinol Metab 13:3–30PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Pieternella Holthuizen
    • 1
  1. 1.Laboratory for Physiological ChemistryState University of UtrechtUtrechtThe Netherlands

Personalised recommendations