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.

  • Letter
  • Published:

Interaction of the erythropoietin and stem-cell-factor receptors

Nature volume 377, pages 242–246 (1995)Cite this article

Abstract

MUTATIONS in the KIT transmembrane protein-tyrosine kinase receptor1 affect erythropoiesis, resulting in fewer committed late progenitors (colony-forming unit erythroid, CFU-E) in the fetal liver2. As the survival and proliferation of CFU-Es depend absolutely on erythropoietin (EPO)3, these results suggest that CFU-Es cannot proliferate or mature further unless both the KIT and EPO receptor4 signalling pathways are functional. How KIT affects proliferation or differentiation of CFU-Es is not clear. Here we show that the KIT ligand SCF (for stem-cell factor) can replace EPO in supporting the growth and survival of HCD57 cells, an EPO-dependent erythroid-progenitor cell line expressing high levels of KIT5. SCF supports the proliferation of 32D cells6 that express KIT only if they also express the EPO receptor. In HCD57 cells, SCF rapidly induces tyrosine phosphorylation of the EPO receptor, and KIT physically associates with the extended box 2 region7 in the cytoplasmic domain of the EPO receptor. Our results indi-cate that KIT may activate the EPO receptor by tyrosine phosphorylation to induce further proliferation and maturation of CFU-Es.

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. Qiu, F. et al. EMBO J. 7, 1003–1011 (1988).

    Article  CAS  Google Scholar 

  2. Nocka, K. et al. Genes Dev. 3, 816–826 (1989).

    Article  CAS  Google Scholar 

  3. Gregory, C. L. J. Cell Physiol. 89, 289–302 (1976).

    Article  CAS  Google Scholar 

  4. D'Andrea, A. D., Lodish, H. F. & Wong, G. G. Cell 57, 277–285 (1989).

    Article  CAS  Google Scholar 

  5. Spivak, J. L. Pham, T., Isaacs, M. & Hankins, W. D. Blood 77, 1228–1233 (1991).

    CAS  PubMed  Google Scholar 

  6. Hilton, D. J. et al. Proc. natn. Acad. Sci. U.S.A. 92, 190–194 (1995).

    Article  ADS  CAS  Google Scholar 

  7. He, T. C. et al. J. biol. Chem. 269, 18291–18294 (1994).

    CAS  PubMed  Google Scholar 

  8. Liu, L., Cutler, R. L., Mui, A. L. F. & Krystal, G. J. biol. Chem. 269, 16774–16779 (1994).

    CAS  PubMed  Google Scholar 

  9. Serve, H. et al. EMBO J. 14, 473–483 (1995).

    Article  CAS  Google Scholar 

  10. Klingmüller, U., Lorenz, U., Cantley, L. C., Neel, B. G. & Lodish, H. F. Cell 80, 729–738 (1995).

    Article  Google Scholar 

  11. Rottapel, R. et al. Molec. cell. Biol. 11, 3043–3051 (1991).

    Article  CAS  Google Scholar 

  12. Tsujimura, T. et al. Blood 83, 2619–2626 (1994).

    CAS  PubMed  Google Scholar 

  13. Yoshimura, A., D'Andrea, A. D. & Lodish, H. F. Proc. natn. Acad. Sci. U.S.A. 87, 4139–4143 (1990).

    Article  ADS  CAS  Google Scholar 

  14. Letwin, K., Yee, S. P. & Pawson, T. Oncogene 3, 621–627 (1988).

    CAS  PubMed  Google Scholar 

  15. Reedijk, M. et al. EMBO J. 11, 1365–1372 (1992).

    Article  CAS  Google Scholar 

  16. Yoshimura, A. & Lodish, H. F. Molec. cell. Biol. 12, 706–715 (1992).

    Article  CAS  Google Scholar 

  17. Witthuhn, B. A. et al. Cell 74, 227–236 (1993).

    Article  CAS  Google Scholar 

  18. Miura, Y., Miura, O., Ihle, J. N. & Aoki, N. J. biol. Chem. 269, 29962–29996 (1994).

    CAS  Google Scholar 

  19. Besmer, P. Curr. Opin. Cell Biol. 3, 939–946 (1991).

    Article  CAS  Google Scholar 

  20. Majumder, S., Brown, K., Qiu, F. & Besmer, P. Molec. cell. Biol. 8, 4896–4903 (1988).

    Article  CAS  Google Scholar 

  21. Sawyer, S. T. & Hankins, W. D. Proc. natn. Acad. Sci. U.S.A. 90, 6849–6853 (1993).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Harvey F. Lodish: To whom correspondence should be addressed.

Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts, 02142, USA

    Hong Wu, Ursula Klingmüller & Harvey F. Lodish

  2. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    Harvey F. Lodish

  3. Molecular Biology Program, Sloan Kettering Institute, New York, New York, 10021, USA

    Peter Besmer

Authors
  1. Hong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ursula Klingmüller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Besmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Harvey F. Lodish
    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

Wu, H., Klingmüller, U., Besmer, P. et al. Interaction of the erythropoietin and stem-cell-factor receptors. Nature 377, 242–246 (1995). https://doi.org/10.1038/377242a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/377242a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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