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Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells

Nature volume 370, pages 153–157 (1994)Cite this article

Abstract

MANY cytokines function through interaction with receptors of the cytokine receptor superfamily. Although lacking catalytic domains, cytokine receptors couple ligand binding to induction of protein tyrosine phosphorylation. Recent studies1–10 have shown that one or more of the Janus kinase family members (Jaks) associate with cytokine receptors and are tyrosine phosphorylated and activated following ligand binding. Here we describe a new Jak family kinase, Jak-3, and demonstrate that Jak-3, and to a lesser extent Jak-1, are tyrosine phosphorylated and Jak-3 is activated in the responses to interleukin-2 and interleukin–4 in T cells and myeloid cells. Jak-3 activation requires the serine-rich, membrane-proximal domain of the interleukin-2 receptor β-chain, but does not require the acidic domain that is required for association and activation of Src family kinases.

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References

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

    Article  CAS  Google Scholar 

  2. Artgetsinger, L. S. et al. Cell 74, 237–244 (1993).

    Article  Google Scholar 

  3. Campbell, G. S. et al. Proc. natn. Acad. Sci. U.S.A. 91, 5232–5236 (1994).

    Article  ADS  CAS  Google Scholar 

  4. Silvennoinen, O. et al. Proc. natn. Acad. Sci. U.S.A. 90, 8429–8433 (1993).

    Article  ADS  CAS  Google Scholar 

  5. Quelle, F. W. et al. Molec. cell. Biol. 14, 4335–4341 (1994).

    Article  CAS  Google Scholar 

  6. Velazquez, L., Fellous, M., Stark, G. R. & Pellegrini, S. Cell 70, 313–322 (1992).

    Article  CAS  Google Scholar 

  7. Muller, M. et al. Nature 366, 129–135 (1993).

    Article  ADS  CAS  Google Scholar 

  8. Watling, D. et al. Nature 366, 166–170 (1993).

    Article  ADS  CAS  Google Scholar 

  9. Stahl, N. et al. Science 263, 92–95 (1994).

    Article  ADS  CAS  Google Scholar 

  10. Narazaki, M. et al. Proc. natn. Acad. Sci. U.S.A. 91, 2285–2289 (1994).

    Article  ADS  CAS  Google Scholar 

  11. Cance, W. G., Craven, R. J., Weiner, T. M. & Liu, E. T. Int. J. Cancer 54, 571–577 (1993).

    Article  CAS  Google Scholar 

  12. Sanchez, M. P., Tapley, P., Saini, S. S., Pulido, D. & Barbacid, M. Proc. natn. Acad. Sci. U.S.A. 91, 1819–1823 (1994).

    Article  ADS  CAS  Google Scholar 

  13. Firmbach-Kraft, I., Byers, M., Shows, T., Dalla-Favera, R. & Krolewski, J. J. Oncogene 5, 1329–1336 (1990).

    CAS  Google Scholar 

  14. Harpur, A. G., Andres, A. C., Ziemiecki, A., Aston, R. R. & Wilks, A. F. Oncogene 7, 1347–1353 (1992).

    CAS  Google Scholar 

  15. Wilks, A. F. et al. Molec. cell. Biol. 11, 2057–2065 (1991).

    Article  CAS  Google Scholar 

  16. Kirken, R. A., Hallgeir, R., Evans, G. A. & Farrar, W. L. J. biol. Chem. 268, 22765–22770 (1993).

    CAS  PubMed  Google Scholar 

  17. D'Andrea, A. D., Fasman, G. D. & Lodish, H. F. Cell 58, 1023–1024 (1989).

    Article  CAS  Google Scholar 

  18. Taniguchi, T. & Minami, Y. Cell 73, 5–8 (1993).

    Article  CAS  Google Scholar 

  19. Russell, S. M. et al. Science 262, 1880–1883 (1993).

    Article  ADS  CAS  Google Scholar 

  20. Kondo, M. et al. Science 262, 1874–1877 (1993).

    Article  ADS  CAS  Google Scholar 

  21. Pellegrini, S. & Schindler, C. Trends biochem. Sci. 18, 338–342 (1993).

    Article  CAS  Google Scholar 

  22. Zhong, Z., Wen, Z. & Darnell, J. E. J. Science 264, 95–98 (1994).

    Article  ADS  CAS  Google Scholar 

  23. Akira, S. et al. Cell 77, 63–71 (1994).

    Article  CAS  Google Scholar 

  24. Wakao, H., Gouilleux, F. & Groner, B. EMBO J. 13, 2182–2191 (1994).

    Article  CAS  Google Scholar 

  25. Larner, A. C. et al. Science 261, 1730–1733 (1993).

    Article  ADS  CAS  Google Scholar 

  26. Kotanides, H. & Reich, N. C. Science 262, 1265–1267 (1993).

    Article  ADS  CAS  Google Scholar 

  27. Schatz, D. G., Oettinger, M. A. & Baltimore, D. Cell 59, 1035–1048 (1989).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  29. Migliaccio, G., Migliaccio, A. R., Kreider, B. L., Rovera, G. & Adamson, J. W. J. Cell Biol. 109, 833–841 (1989).

    Article  CAS  Google Scholar 

  30. Johnston, J. A. et al. Nature 370, 151–153 (1994).

    Article  ADS  CAS  Google Scholar 

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Author notes

  1. Osamu Miura

    Present address: Department of First Internal Medicine, Tokyo Medical and Dental University, Tokyo, Japan

Authors and Affiliations

  1. Department of Biochemistry, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee, 38105, USA

    Bruce A. Witthuhn, Olli Silvennoinen, Osamu Miura, Christopher Cwik & James N. Ihle

  2. School of Medicine, UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-7295, USA

    Edison T. Liu

  3. Department of Biology, UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-7295, USA

    Koon Siew Lai

Authors
  1. Bruce A. Witthuhn
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  2. Olli Silvennoinen
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  3. Osamu Miura
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  4. Koon Siew Lai
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  5. Christopher Cwik
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  6. Edison T. Liu
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  7. James N. Ihle
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Witthuhn, B., Silvennoinen, O., Miura, O. et al. Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells. Nature 370, 153–157 (1994). https://doi.org/10.1038/370153a0

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