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.

  • Brief Communication
  • Published:

PDGF-D, a new protease-activated growth factor

Abstract

Platelet-derived growth factor (PDGF) has been directly implicated in developmental and physiological processes1,2,3,4,5, as well as in human cancer, fibrotic diseases and arteriosclerosis6. The PDGF family currently consists of at least three gene products, PDGF-A, PDGF-B and PDGF-C, which selectively signal through two PDGF receptors (PDGFRs) to regulate diverse cellular functions. After two decades of searching, PDGF-A and B were the only ligands identified for PDGFRs. Recently, however, database mining has resulted in the discovery of a third member of the PDGF family, PDGF-C7,8, a functional analogue of PDGF-A that requires proteolytic activation. PDGF-A and PDGF-C selectively activate PDGFR-α7,9,10, whereas PDGF-B activates both PDGFR-α and PDGFR-β9,11. Here we identify and characterize a new member of the PDGF family, PDGF D, which also requires proteolytic activation. Recombinant, purified PDGF-D induces DNA synthesis and growth in cells expressing PDGFRs. In cells expressing individual PDGFRs, PDGF-D binds to and activates PDGFR-β but not PDGFR-α. However, in cells expressing both PDGFRs, PDGF-D activates both receptors. This indicates that PDGFR-α activation may result from PDGFR-α/β heterodimerization.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Nucleotide and deduced amino-acid sequence of human PDGF-D.
Figure 2: TaqMan expression analysis, purification and biological activity of PDGF-DD.
Figure 3: PDGF-DD-binding, tyrosine-phosphorylation and heterodimerization of PDGFRs.

Similar content being viewed by others

References

  1. Bostrom, H. et al. Cell 85, 863–873 (1996).

    Article  CAS  Google Scholar 

  2. Leveen, P. et al. Genes Dev. 8, 1875–1887 (1994).

    Article  CAS  Google Scholar 

  3. Lindahl, P., Johansson, B., Leveen, P. & Betsholtz, C. Science 277, 242–245 (1997).

    Article  CAS  Google Scholar 

  4. Soriano, P. Genes Dev. 8, 1888–1896 (1994).

    Article  CAS  Google Scholar 

  5. Soriano, P. Development 124, 2691–2700 (1997).

    CAS  Google Scholar 

  6. Heldin, C. & Westermark, B. Physiol. Rev. 79, 1283–1316 (1999).

    Article  CAS  Google Scholar 

  7. Li, X., Ponten, A., Aase, K., Karlsson, L. & Abramsson, A. Nature Cell Biol. 2, 302–309 (2000).

    Article  CAS  Google Scholar 

  8. Hamada, T., Ui-Tei, K. & Miyata, Y. FEBS Lett. 475, 97–102 (2000).

    Article  CAS  Google Scholar 

  9. Matsui, T. et al. Science 243, 800–804 (1989).

    Article  CAS  Google Scholar 

  10. Claesson-Welsh, L., Eriksson, A., Westermark, B. & Heldin, C. Proc. Natl Acad. Sci. USA 86, 4917–4921 (1989).

    Article  CAS  Google Scholar 

  11. Bowen-Pope, D., Hart, C. & Seifert, R. J. Biol. Chem. 264, 2502–2508 (1989).

    CAS  Google Scholar 

  12. Nakai, K. & Kanehisa, M. Genomics 14, 897–911 (1992).

    Article  CAS  Google Scholar 

  13. Sonnhammer, E., Eddy, S. & Durbin, R. Proteins 28, 405–420 (1997).

    Article  CAS  Google Scholar 

  14. Bucher, P. & Bairoch, A. Proc. Int. Conf. Intell. Syst. Mol. Biol. 2, 53–61 (1994).

    CAS  Google Scholar 

  15. Thielens, N., Bersch, B., Hernandez, J. & Arlaud, G. Immunopharmacology 42, 3–13 (1999).

    Article  CAS  Google Scholar 

  16. Giese, N., Robbins, K. & Aaronson, S. Science 236, 1315–1318 (1987).

    Article  CAS  Google Scholar 

  17. LaRochelle, W., May-Siroff, M., Robbins, K. & Aaronson, S. Genes Dev. 5, 1191–1199 (1991).

    Article  CAS  Google Scholar 

  18. Heid, C., Stevens, J., Livak, K. & Williams, P. Genome Res. 6, 986–994 (1996).

    Article  CAS  Google Scholar 

  19. Lokker, N. et al. J. Biol. Chem. 272, 33037–33044 (1997).

    Article  CAS  Google Scholar 

  20. Pignatelli, D., Magalhaes, M. & Magalhaes, M. Horm. Metab. Res. 30, 464–474 (1998).

    Article  CAS  Google Scholar 

  21. Bergsten, E. et al. Nature Cell Biol. 3, 512–516 (2001) (this issue).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank D. Andrew, S. Minskoff and B. Gould-Rothberg for discussions, and S. Colman for chromosome mapping.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to William J. LaRochelle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

LaRochelle, W., Jeffers, M., McDonald, W. et al. PDGF-D, a new protease-activated growth factor. Nat Cell Biol 3, 517–521 (2001). https://doi.org/10.1038/35074593

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/35074593

This article is cited by

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