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  • The EMBO Journal (2001) 20, 5431 - 5442
  • doi:10.1093/emboj/20.19.5431

A completely foreign receptor can mediate an interferon-big gamma-like response

Birgit Strobl1,5, Velmurugesan Arulampalam1,5, Hayaatun Is'harc1, Sally J. Newman1, Jörg F. Schlaak1, Diane Watling1, Ana P. Costa-Pereira1, Fred Schaper2, Iris Behrmann2, Kathleen C.F. Sheehan3, Robert D. Schreiber3, Friedemann Horn4, Peter C. Heinrich2 and Ian M. Kerr1

  1. Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
  2. Biochemistry, RWTH, Pauwelsstrasse, 52057 Aachen, Germany
  3. Pathology and Immunology, Center for Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
  4. Institute for Clinical Immunology, Molecular Immunology, Delitzscher Strasse 141, 04129 Leipzig, Germany
  5. B.Strobl and V.Arulampalam contributed equally to this work

Correspondence to:

Ian M. Kerr, E-mail: kerr@icrf.icnet.uk

Received 3 July 2001; Accepted 9 August 2001; Revised 9 August 2001

A tripartite receptor comprising the external region of the erythropoietin (Epo) receptor, the transmembrane and JAK-binding domains of the gp130 subunit of the interleukin-6 (IL-6) receptor, and a seven amino acid STAT1 recruitment motif (Y440) from the interferon (IFN)-gamma receptor, efficiently mediates an IFN-gamma-like response. An analogous completely foreign chimeric receptor in which the Y440 motif is replaced with the Y905 motif from gp130 also mediates an IFN-gamma-like response, but less efficiently. The IFNGR1 signal-transducing subunit of the IFN-gamma receptor is tyrosine phosphorylated through the chimeric receptors and the endogenous IL-6 and OSM receptors. Cross phosphorylation of IFNGR1 is not, however, required for the IFN-gamma-like response through the chimeric receptors, nor does it mediate an IFN-gamma-like response to IL-6 or OSM. The data argue strongly for modular JAK/STAT signalling and against any rigid structural organization for the 'pathways' involved. They emphasize the likely high degree of overlap between the signals generated from disparate JAK–receptor complexes and show that relatively minor changes in such complexes can profoundly affect the response.

  • Keywords:

    • cytokine,
    • interferon,
    • modular signalling,
    • receptor cross phosphorylation