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Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs

Abstract

THE FLT3/FLK2 receptor tyrosine kinase is closely related to two receptors, c-Kit and c-Fms, which function with their respective ligands, Kit ligand and macrophage colony-stimulating factor to control differentiation of haematopoietic and non-haematopoietic cells1–5. FLT3/FLK2 is thought to be present on haematopoietic stem cells and found in brain, placenta and testis3–5. We have purified to homogeneity and partially sequenced a soluble form of the FLT3/FLK2 ligand produced by mouse thymic stromal cells. We isolated several mouse and human complementary DNAs that encode polypeptides with identical N termini and different C termini. Some variants contain hydrophobic transmembrane segments, suggesting that processing may be required to release soluble lig-and. The purified ligand enhances the response of mouse stem cells and a primitive human progenitor cell population to other growth factors such as interleukins IL-3 and IL-6 and to granulocyte-macrophage colony-stimulating factor, and also stimulates fetal thymocytes.

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References

  1. Sherr, C. J. Blood 75, 1–12 (1990).

    CAS  PubMed  Google Scholar 

  2. Witte, O. N. Cell 63, 5–6 (1990).

    Article  CAS  Google Scholar 

  3. Rosnet, O., Marchetto, S., deLapeyriere, O. & Birnbaum, D. Oncogene 6, 1641–1650 (1991).

    CAS  PubMed  Google Scholar 

  4. Rosnet, O. et al. Blood 82, 1110–1119 (1993).

    CAS  PubMed  Google Scholar 

  5. Matthews, W., Jordan, C. T., Wiegand, G. W., Pardoll, D. & Lemischka, I. R. Cell 65, 1–20 (1991).

    Article  Google Scholar 

  6. Palacios, R. & Steinmetz, M. Cell 41, 727–734 (1985).

    Article  CAS  Google Scholar 

  7. Schlessinger, J. & Ullrich, A. Neuron 9, 383–391 (1991).

    Article  Google Scholar 

  8. Galy, A. H. M., de Waal Malefyt, R., Barcena, A., Mohan-Peterson, S. & Spits, H. Thymus 22, 13–33 (1993).

    CAS  PubMed  Google Scholar 

  9. Bazan, J. F. Cell 65, 9–10 (1991).

    Article  CAS  Google Scholar 

  10. Pandit, J., Bohm, A., Jancarik, J., Halenbeck, R., Koths, K. & Kim, S. H. Science 258, 1358–1362 (1992).

    Article  ADS  CAS  Google Scholar 

  11. Sprang, S. R. & Bazan, J. F. Curr. Opin. struct. Biol. 3, 815–827 (1993).

    Article  CAS  Google Scholar 

  12. Godfrey, D. I., Zlotnik, A. & Suda, T. J. Immun. 149, 2281–2285 (1992).

    CAS  PubMed  Google Scholar 

  13. Mosmann, T. R. J. Immunol. Meth. 65, 55–63 (1983).

    Article  CAS  Google Scholar 

  14. Maroc, N. et al. Oncogene 8, 909–918 (1991).

    Google Scholar 

  15. McKenzie, A. N. J. et al. Proc. natn. Acad. Sci. U.S.A. 90, 3735–3739 (1993).

    Article  ADS  CAS  Google Scholar 

  16. Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    Article  ADS  CAS  Google Scholar 

  17. Zurawski, S. M. & Zurawski, G. EMBO J. 11, 3905–3910 (1992).

    Article  CAS  Google Scholar 

  18. Zurawski, S. M., Vega, F., Huyghe, B. & Zurawski, G. EMBO J. 12, 2663–2670 (1993).

    Article  CAS  Google Scholar 

  19. Spangrude, G. J., Heimfeld, S. & Weissman, I. L. Science 241, 58–62 (1988).

    Article  ADS  CAS  Google Scholar 

  20. Heimfeld, S., Hudak, S., Weissman, I. L. & Rennick, D. Proc. natn. Acad. Sci. U.S.A. 88, 9902–9906 (1991).

    Article  ADS  CAS  Google Scholar 

  21. Bárcena, A. et al. Blood (in the press).

Download references

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Hannum, C., Culpepper, J., Campbell, D. et al. Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs. Nature 368, 643–648 (1994). https://doi.org/10.1038/368643a0

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