Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

New insights into heparin-induced FGF oligomerization

Nature Structural Biology volume 5, pages 527–530 (1998)Cite this article

Abstract

Fibroblast growth factors (FGFs) play important roles in a variety of developmental processes in mammals. The dependence of their activity on heparin binding has been a puzzle that, in recent years, has been the subject of active investigation. Recent structural analyses on complexes of FGFs with heparin fragments or heparin analogs have unveiled the extreme complexity of these systems.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schematic diagram of the repeating disaccharide unit in heparin.
Figure 2: FGF-2 bound to a heparin hexasaccharide18.
Figure 3: Stereo view of FGF-1 dimer 'A' bound to a heparin decasaccharide16.
Figure 4: Three possible configurations for heparin-induced FGF oligomers: a, a trans dimer; b, a cis dimer; and c, a FGF tetramer resulting from trans and cis oligomerization.

References

  1. Moscatelli, D., Presta, M. & Rifkin, D.B. Proc. Natl. Acad. Sci. USA 83, 2091–2095 (1986).

    Article  CAS  Google Scholar 

  2. Folkman, J. & Klagsbrun, M. Science 235, 442–447 (1987).

    Article  CAS  Google Scholar 

  3. Fallon, J.F., et al. Science 264, 104–107 ( 1994).

    Article  CAS  Google Scholar 

  4. Colvin, J.S., Bohne, B.A., Harding, G.W., McEwen, D.G. & Ornitz, D.M. Nature Genet. 12, 390– 397 (1996).

    Article  CAS  Google Scholar 

  5. Ortega, S., Ittmann, M., Tsang, S.H., Ehrlich, M. & Basilico, C. Proc. Natl. Acad. Sci. USA 95, 5672–5677 (1998).

    Article  CAS  Google Scholar 

  6. Slack, J.M., Darlington, B.G., Heath, J.K. & Godsave, S.F. Nature 326, 197–200 (1987).

    Article  CAS  Google Scholar 

  7. Deng, C., Wynshaw-Boris, A., Zhou, F., Kuo, A. & Leder, P. Cell 84, 911–921 ( 1996).

    Article  CAS  Google Scholar 

  8. Ornitz, D.M., et al. J Biol Chem 271, 15292–15297 (1996).

    Article  CAS  Google Scholar 

  9. Ornitz, D.M. & Waksman, G. In growth factors and wound healing: basic science and potential clinical applications (eds. Ziegler, T.R., Pierce, G.F. & Herndon, D.N.) 151–174 (Springer-Verlag, New York; 1997).

    Book  Google Scholar 

  10. Yayon, A., Klagsbrun, M., Esko, J.D., Leder, P. & Ornitz, D.M. Cell 64, 841–848 (1991).

    Article  CAS  Google Scholar 

  11. Ornitz, D.M. et al. Mol. Cell. Biol. 12, 240–247 (1992).

    Article  CAS  Google Scholar 

  12. Pantoliano, M.W. et al. Biochemistry 33, 10229–10248 (1994).

    Article  CAS  Google Scholar 

  13. Spivak-Kroizman, T. et al. Cell 79, 1015–1024 (1994).

    Article  CAS  Google Scholar 

  14. Moy, F.J. et al. Biochemistry 36, 4782–4791 (1997).

    Article  CAS  Google Scholar 

  15. Herr, A.B., Ornitz, D.M., Sasisekharan, R., Venkataraman, G. & Waksman, G. J. Biol. Chem. 272, 16382– 16389 (1997).

    Article  CAS  Google Scholar 

  16. DiGabriele, A.D. et al. Nature, in the press (1998).

  17. Zhu, X., Hsu, B.T. & Rees, D.C. Structure 1, 27–34 ( 1993).

    Article  CAS  Google Scholar 

  18. Faham, S., Hileman, R.E., Fromm, J.R., Linhardt, R.J. & Rees, D.C. Science 271, 1116– 1120 (1996).

    Article  CAS  Google Scholar 

  19. Ornitz, D.M. et al. Science 268, 432–436 ( 1995).

    Article  CAS  Google Scholar 

  20. Mulloy, B., Forster, M.J., Jones, C. & Davies, D.B. Biochem. J. 293, 849–848 (1993).

    Article  CAS  Google Scholar 

  21. Guimond, S., Maccarana, M., Olwin, B.B., Lindahl, U. & Rapraegar, A.C. J. Biol. Chem. 268, 23906– 23914 (1993).

    CAS  PubMed  Google Scholar 

  22. Lee, A.K. & Lander, A.D. Proc. Natl. Acad. Sci. USA 88, 2768–2772 (1991).

    Article  CAS  Google Scholar 

  23. Kan, M. et al. Science 259, 1918–1921 ( 1993).

    Article  CAS  Google Scholar 

  24. Mikhalov, D., Linhardt, R.J. & Mayo, K.H. Biochem. J. 328, 51–61 ( 1997).

    Article  Google Scholar 

Download references

Acknowledgements

We thank D.M. Ornitz for comments on the manuscript.

Author information

Authors and Affiliations

  1. the Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Campus Box 8231, 660 South Euclid Av., Saint Louis, 63110, Missouri, USA

    Gabriel Waksman & Andrew B. Herr

Authors
  1. Gabriel Waksman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew B. Herr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriel Waksman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Waksman, G., Herr, A. New insights into heparin-induced FGF oligomerization. Nat Struct Mol Biol 5, 527–530 (1998). https://doi.org/10.1038/778

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/778

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing