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.

  • Research Article
  • Published:

Engineering epidermal growth factor for enhanced mitogenic potency

Nature Biotechnology volume 14, pages 1696–1699 (1996)Cite this article

Abstract

Successful use of growth factois in therapeutic and bioprocessig application requires overcoming two attenuation mechanisms: growth factor depletion and receptor down-regulation. current ameliorative strategies use physiologically inappropriate high growth-factor concentrations, along with periodic media refeeding in vitro and reinjection or controlled-release devices in vivo. We demonstrate a new approach derived from understanding how these attenuation mechanisms arise from ligand/receptor trafficking processes. Specifically, a recombinant epidermal growth factor (EGF) mutant with reduced receptor binding affinity is a more potent migogenic stimulus of fibroblasts than natural EGF or transforming growth factor alpha because of its altered trafficking properties.

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

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

Similar content being viewed by others

References

  1. Sporn, M., and Roberts, A.B. (eds.). 1990. Peptide growth factors and their receptors. Springer-Verlag, Berlin.

    Google Scholar 

  2. Pimental, E. 1990. Handbook of growth factors, volume II: peptlde growth factors. CRC Press, Boca Baton, FL

    Google Scholar 

  3. Wolfe, R.A. 1993. Media for cell culture, pp. 142–156 in Biotechnology, volume 3: bioprocessing. Stephanopolous, G. (ed.). VCH Publishers Inc., New York, NY.

    Google Scholar 

  4. Meyer-lngold, W. 1993. Wound therapy: growth factors as agents to promote healing. Trends Blotechnol. 11: 387–392.

    Article  Google Scholar 

  5. Langer, R., and Vacanti, J.P. 1993. Tissue engineering. Science 260: 920–926.

    Article  CAS  Google Scholar 

  6. Krueger, G.G., Morgan, J.R., Jorgensen, C.M., Schmidt, L, Li, H.L., Kwan, M.K., et al. 1994. Genetically modified skin to treat disease: potential and limitations. J. Invest. Dermatol. 103: 768–843.

    Article  Google Scholar 

  7. Wiley, H.S. 1992. Receptors: topology, dynamics, and regulation, pp. 113–142 in Membrane dynamics and signaling. JAI Press Inc., Greenwich, CT.

    Google Scholar 

  8. Moody, P.C.E., and Wilkinson, A. 1990. Protein engineering. Oxford University Press, New York.

    Google Scholar 

  9. Reddy, C.C., Wells, A., and Lauffenburger, D.A. 1994. Proliferative response of fibroblasts expressing Internalization-deficient epidermal growth factor (EGF) receptors is altered via differential EGF depletion effect. Biotechnol. Prog. 10: 377–384.

    Article  CAS  Google Scholar 

  10. Reddy, C.C., Wells, A., and Lauffenburger, D.A. 1996. Receptor-mediated effects on ligand availability influence relative mitogenic potencies of epidermal growth factor and transforming growth factor α. J. Cell. Physiol. 166: 512–522.

    Article  CAS  Google Scholar 

  11. Tadaki, D.K., and Niyogi, S.K. 1993. The functional importance of hydropho-bicity of the tyroslne at position 13 of human epidermal growth factor in receptor binding. J. Biol. Chem. 268: 10114–10119.

    CAS  PubMed  Google Scholar 

  12. French, A.R., Tadaki, D.K., Niyogi, S.K., and Lauffenburger, D.A. 1995. Intracellular trafficking of epidermal growth factor family ligands Is directly influenced by the pH sensitivity of the receptor/ligand interaction. J. Biol. Chem. 270: 4334–4340.

    Article  CAS  Google Scholar 

  13. Chang, D.Z., Wu, Z., and Ciardelli, T.L. 1996. A point mutation in interleukin-2 that alters ligand internalization. J. Biol. Chem. 271: 13349–13355.

    Article  CAS  Google Scholar 

  14. Chen, P., Gupta, K., and Wells, A. 1994. Cell movement elicited by the epidermal growth factor requires kinase and autophosphorylation but is separable from mitogenesis. J. Cell. Biol. 124: 547–555.

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Douglas A. Lauffenburger: e-mail: lauffen@mit.edu

Authors and Affiliations

  1. Department of Chemical Engineering, University of I llinois at Urbana-Champaign, Urbana, IL, 61801

    Cartikeya C. Reddy

  2. Department of Chemical Engineering and Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139

    Cartikeya C. Reddy & Douglas A. Lauffenburger

  3. The Protein Engineering and Program, Biological Division, Oak Ridge National Laboratory, Oak Ridge, TN, 37831

    Salil K. Niyogi

  4. Department of Pathology, University of Alabama at Birmingham and Birmingham Veterans Administration Medical Center, Birmingham, AL, 35294

    Alan Wells

  5. Department of Pathology, University of Utah, Salt Lake City, UT, 84123

    H. Steven Wiley

Authors
  1. Cartikeya C. Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Salil K. Niyogi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alan Wells
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Steven Wiley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Douglas A. Lauffenburger
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reddy, C., Niyogi, S., Wells, A. et al. Engineering epidermal growth factor for enhanced mitogenic potency. Nat Biotechnol 14, 1696–1699 (1996). https://doi.org/10.1038/nbt1296-1696

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt1296-1696

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