Skip to main content

Advertisement

SpringerLink
Log in

Heterodimerization of the IL-2 receptor β- and γ-chain cytoplasmic domains is required for signalling

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

THE interaction of interleukin-2 (IL-2) and IL-2 receptors criti-cally regulates the T-cell immune response following antigen activation1,2. IL-2 can signal through high or intermediate affinity receptors which contain IL-2Rα (refs 3, 4) + β (refs5–8) + γ (ref. 9) or β + γ chains, respectively. IL-2Rγ is a common γ chain, γc, also shared by the IL-7 (ref. 10) and IL-4 (refs 11,12) receptors, which when mutated results in X-linked severe combined immunodeficiency13. Using chimaeric receptor constructs together with monoclonal or bispecific antibodies we demonstrate here that IL-2 signalling requires ligand-induced extracellular-domain-mediated heterodimerization of the β- and γc-chain cytoplasmic domains. Anti-I L-2Rα monoclonal antibodies trigger proliferation of cells transfected with chimaeric constructs in which the extracel-lular domains of IL-2Rβ and γc are replaced by that of IL-2Rα. Other experiments using chimaeric constructs indicated that IL-2 binds monomerically and monovalently to IL-2Rα and that the β-transmembrane domain is not required for receptor chain inter-actions. Finally, we provide a method for mapping residues in the γc cytoplasmic domain even in cells that constitutively express γc.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Leonard, W. J., Noguchi, M., Russell, S. M. & McBride, O. W. Immun. Rev. 138, 61–86 (1994).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  3. Leonard, W. J. et al. Nature 311, 625–631 (1984).

    Article  ADS  Google Scholar 

  4. Nikaido, T. et al. Nature 311, 631–635 (1984).

    Article  ADS  CAS  Google Scholar 

  5. Sharon, M., Klausner, R. D., Cullen, B. R., Chizzonite, R. & Leonard, W. J. Science 234, 859–863 (1986).

    Article  ADS  CAS  Google Scholar 

  6. Tsudo, M., Kozak, R. W., Goldman, C. K. & Waldmann, T. A. Proc. natn. Acad. Sci. U.S.A. 83, 9694–9698 (1986).

    Article  ADS  CAS  Google Scholar 

  7. Teshigawara, K., Wang, H.-M., Kato, K. & Smith, K. A. J. exp. Med. 165, 223–238 (1987).

    Article  CAS  Google Scholar 

  8. Hatakeyama, M. et al. Science 244, 551–556 (1989).

    Article  ADS  CAS  Google Scholar 

  9. Takeshita, T. et al. Science 257, 379–382 (1992).

    Article  ADS  CAS  Google Scholar 

  10. Noguchi, M. et al. Science 262, 1877–1880 (1993).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  13. Noguchi, M. et al. Cell 73, 147–157 (1993).

    Article  CAS  Google Scholar 

  14. Otani, H. et al. Proc. natn. Acad. Sci. U.S.A. 89, 2789–2793 (1992).

    Article  ADS  CAS  Google Scholar 

  15. Cao, X. et al. Proc. natn. Acad. Sci. U.S.A. 90, 8464–8468 (1993).

    Article  ADS  CAS  Google Scholar 

  16. Kumaki, S. et al. Biochem. biophys. Res. Commun. 193, 356–363 (1993).

    Article  CAS  Google Scholar 

  17. Hatakeyama, M. et al. Cell 59, 837–845 (1989).

    Article  CAS  Google Scholar 

  18. Exley, M., Terhorst, C. & Wileman, T. Semin. Immun. 3, 283–297 (1991).

    CAS  Google Scholar 

  19. Asao, H. et al. Proc. natn. Acad. Sci. U.S.A. 90, 4127–4131 (1993).

    Article  ADS  CAS  Google Scholar 

  20. Leonard, W. J., Depper, J. M., Robb, R. J., Waldmann, T. A. & Greene, W. C. Proc. natn. Acad. Sci. U.S.A. 80, 6957–6961 (1983).

    Article  ADS  CAS  Google Scholar 

  21. Leonard, W. J. et al. Nature 300, 267–269 (1982).

    Article  ADS  CAS  Google Scholar 

  22. Schlessinger, J. & Ullrich, A. Neuron 9, 383–391 (1992).

    Article  CAS  Google Scholar 

  23. Stahl, N. & Yancopoulos, G. D. Cell 74, 587–590 (1993).

    Article  CAS  Google Scholar 

  24. Kahn, C. R., Baird, K., Flier, J. S. & Jarrett, D. B. J. clin. Invest. 60, 1094–1106 (1977).

    Article  CAS  Google Scholar 

  25. Tartaglia, L. A. et al. Proc. natn. Acad. Sci. U.S.A. 88, 9292–9296 (1991).

    Article  ADS  CAS  Google Scholar 

  26. Francois, C., Boeffard, F., Kaluza, B., Weidle, U. & Jacques, Y. J. Immun. 150, 4610–4619 (1993).

    CAS  Google Scholar 

  27. Takebe, Y. et al. Molec. cell. Biol. 8, 466–472 (1988).

    Article  CAS  Google Scholar 

  28. Gnarra, J. R. et al. Proc. natn. Acad. Sci. U.S.A. 87, 3440–3444 (1990).

    Article  ADS  CAS  Google Scholar 

  29. Higuchi, R., Krummel, B. & Saiki, R. K. Nucleic Acids Res. 16, 7351–7367 (1988).

    Article  CAS  Google Scholar 

  30. Noguchi, M., Adelstein, S., Cao, X. & Leonard, W. J. J. biol. Chem. 268, 13601–13608 (1993).

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Yoshlaki Nakamura

    Present address: Second Department of Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan

  2. Sarah A. Mess

    Present address: University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

  3. Michael Erdos

    Present address: National Center for Human Genome Research, NIH, Bethesda, Maryland, 20892, USA

  4. Stephen Adelstein

    Present address: Department of Immunology, Allergy and Infectious Disease, The St George Hospital, Kogarah, New South Wales, 2217, Australia

Authors and Affiliations

  1. Section on Pulmonary and Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bid. 10, Rm 7N244, Bethesda, Maryland, 20892, USA

    Yoshlaki Nakamura, Sarah M. Russell, Sarah A. Mess, Michael Friedmann, Michael Erdos, Stephen Adelstein & Warren J. Leonard

  2. INSERM Unite 211, Institut de Biologie, 9 Quai Moncousu, 44035, Nantes Cedex, France

    Christine Francois, Yannick Jacques & Stephen Adelstein

Authors
  1. Yoshlaki Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah M. Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sarah A. Mess
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Friedmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Erdos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christine Francois
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yannick Jacques
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stephen Adelstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Warren J. Leonard
    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

Nakamura, Y., Russell, S., Mess, S. et al. Heterodimerization of the IL-2 receptor β- and γ-chain cytoplasmic domains is required for signalling. Nature 369, 330–333 (1994). https://doi.org/10.1038/369330a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/369330a0

  • Springer Nature Limited

This article is cited by

Search

Navigation