Transcriptional Diversity in Rat Insulin-Like Growth Factor I Gene Expression

  • Charles T. RobertsJr.
  • William L. LoweJr.
  • Derek LeRoith


Insulin-like growth factor I (IGF-I), or Somatomedin C, is a member of a family of insulin-like peptides which also includes insulin itself, insulin-like growth factor II (IGF-II) or multiplication-stimulating activity (MSA), and, in some schemes, relaxin (1,2,3). The IGFs are similar to proinsulin in that they contain B and A domains separated by a C peptide sequence, but differ in that the mature IGF-I proteins retain their C peptide moeities and therefore consist of single polypeptide chains. Additionally, the mature forms of the IGFs contain a carboxy-terminal D domain not found in insulin (2,4,5). Finally, as discussed in more detail below with respect to IGF-I, cDNA sequences corresponding to IGF-I and IGF-II mRNAs suggest the presence of an additional carboxy-terminal E peptide predicted to be a component of the IGF-I and IGF-II pro-hormones (6,7,8,9).


Transcriptional Diversity Multiple Size Classis Signal Peptide Amino Acid Sequence 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1..
    T.L. Blundell, S. Bedarker, and R.E. Humbel, Tertiary structures, receptor binding, and antigenicity of insulin-like growth factors. Fed. Proc. 42:2592 (1983).PubMedGoogle Scholar
  2. 2.
    E. Rinderknecht and R.E. Humbel, The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J. Biol. Chem. 253:2769 (1978a).PubMedGoogle Scholar
  3. 3.
    M.O. Dayhoff, Atlas of Protein Sequence and Structure, p. 150, (National Biomedical Research Foundation, Washington, D.C.) (1978).Google Scholar
  4. 4.
    D.C. Klapper, M.E. Svoboda, and J.J. Van Wyk, Sequence analysis of somatomedin-C: confirmation of identity with insulin-like growth factor II. FEBS Letters 89:283 (1983).Google Scholar
  5. 5.
    E. Rinderknecht and R.E. Humbel, Primary structure of insulin-like growth factor II. FEBS Letters 89:283 (1978b).PubMedCrossRefGoogle Scholar
  6. 6.
    M. Jansen, F.M.A. van Schaik, A.T. Ricker, B. Bullock, D.E. Woods, K.H. Gabbay, A.L. Nussbaum, J.S. Sussenbach, and J.L. van den Brande, Sequence of cDNA encoding human insulin-like growth factor I precursor. Nature 306:609 (1983).PubMedCrossRefGoogle Scholar
  7. 7.
    A. Ullrich, C.H. Berman, T.J. Dull, A. Gray, and J.M. Lee, Isolation of the human insulin-like growth factor I gene using a single synthetic DNA probe. EMBO Journal 3:361 (1984).PubMedGoogle Scholar
  8. 8.
    G.I. Bell, J.P. Merryweather, R. Sanchez-Pescador, M.M. Stempien, L. Preistly, S. Scott, and L. B. Rall, A cDNA clone encoding human preproinsulin-like growth factor II. Nature 310:775 (1984).PubMedCrossRefGoogle Scholar
  9. 9.
    H.R. Whitfield, C.B. Bruno, R. Frunzio, J.R. Terrell, S.P. Nissley, and M.M. Rechler, Isolation of a cDNA clone encoding rat insulin-like growth factor-II precursor. Nature 312:277 (1984).PubMedCrossRefGoogle Scholar
  10. 10.
    E.R. Froesch, C. Schmid, J. Schwander, and J. Zapf, Actions of insulin-like growth factors. Ann. Rev. Physiol. 47:443 (1985).CrossRefGoogle Scholar
  11. 11.
    A.J. D’Ercole, A.D. Stiles, and L.E. Underwood, Tissue concentrations of somatomedin C: Further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc. Nat. Acad. Sci. (USA) 81:935 (1984).CrossRefGoogle Scholar
  12. 12.
    C.T. Roberts, Jr., S.R. Lasky, W.L. Lowe, Jr., W.T. Seaman, and D. LeRoith, Molecular cloning of rat insulin-like growth factor I complementary deoxyribonucleic acids: differential messenger ribonucleic acid processing and regulation by growth hormone in extrahepatic tissues. Mol. Endocrinol. 1:243 (1987).PubMedCrossRefGoogle Scholar
  13. 13.
    C.T. Roberts, Jr., S.R. Lasky, W.L. Lowe, Jr., and D. LeRoith, Rat IGF-I cDNAs contain multiple 5′-untranslated regions. Biochem. Biophys. Res. Comm. 146:1154 (1987).PubMedCrossRefGoogle Scholar
  14. 14.
    A. Shimatsu and P. Rotwein, Sequence of two rat insulin-like growth factor I mRNAs differing within the 5′-untranslated region. Nuc. Acids Res. 15:7196 (1988).CrossRefGoogle Scholar
  15. 15.
    A. Shimatsu and P. Rotwein Mosaic evolution of the insulin-like growth factors. J. Biol. Chem. 262:7894 (1987).PubMedGoogle Scholar
  16. 16.
    L. Chiariotti, A.L. Brown, R. Frunzio, D.R. Clemmons, M.M. Rechler, and C.B. Bruni, Structure of the rat insulin-like growth factor II transcriptional unit. Mol. Endocrinol. 2:1115 (1988).PubMedCrossRefGoogle Scholar
  17. 17.
    P. Rotwein, R.J. Folz, and J.J. Gordon, Biosynthesis of human insulin-like growth factor I (IGF-I). J. Biol. Chem 262:11807 (1987).PubMedGoogle Scholar
  18. 18.
    M.R. Rebagliati, and D.A. Melton, Antisense RNA injections in fertilized frog eggs reveal an RNA duplex unwinding activity. Cell 48:599 (1987).PubMedCrossRefGoogle Scholar
  19. 19.
    B.L. Bass and H. Weintraub, A developmentally regulated activity that unwinds RNA duplexes. Cell 48:607 (1987).PubMedCrossRefGoogle Scholar
  20. 20.
    R.W. Wagner and K. Nishikawa, Cell cycle expression of RNA duplex unwindase activity in mammalian cells. Mol. Cell. Biol. 8:770 (1988).PubMedGoogle Scholar
  21. 21.
    W.L. Lowe, Jr., C.T. Roberts, Jr., S.R. Lasky, and D. LeRoith, Differential expression of alternative 5′-untranslated regions in mRNAs encoding rat insulin-like growth factor I. Proc. Natl. Acad. Sci. (USA) 84:8946 (1987).CrossRefGoogle Scholar
  22. 22.
    P. Rotwein, Two insulin-like growth factor I messenger RNAs are expressed in human liver. Proc. Natl. Acad. Sci. (USA) 83:77 (1986).CrossRefGoogle Scholar
  23. 23.
    P. Rotwein, K.M. Pollock, D.K. Didier, and G.G. Krivi, Organization and sequence of the human insulin-like growth factor I gene. J. Biol. Chem. 261:4828 (1986).PubMedGoogle Scholar
  24. 24.
    G.I. Bell, M.M. Stempien, N.M. Fong, and L.B. Rall, Sequence of liver cDNAs encoding two different mouse insulin-like growth factor I precursors. Nuc. Acids Res. 14:7873 (1986).CrossRefGoogle Scholar
  25. 25.
    A. Tavakkol, F.A. Simmen, and R.C.M. Simmen, Porcine insulin-like growth factor I (pIGF-I): complementary deoxyribonucleic acid cloning and uterine expression of messenger ribonucleic acid encoding evolutionarily conserved IGF-I peptides. Mol. Endocrinol. 2:674 (1988).PubMedCrossRefGoogle Scholar
  26. 26.
    W.L. Lowe, Jr., S.R. Lasky, D. LeRoith, and C.T. Roberts, Jr., Distribution and regulation of rat insulin-like growth factor I messenger ribonucleic acids encoding alternative carboxyterminal E peptides: evidence for differential processing and regulation in liver. Mol. Endocrinol. 2:528 (1988).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Charles T. RobertsJr.
    • 1
  • William L. LoweJr.
    • 1
  • Derek LeRoith
    • 1
  1. 1.Section of Molecular and Cellular Physiology, Diabetes BranchNational Institutes of HealthBethesdaUSA

Personalised recommendations