TY - JOUR
T1 - A completely foreign receptor can mediate an interferon-γ-like response
AU - Strobl, Birgit
AU - Arulampalam, Velmurugesan
AU - Is'Harc, Hayaatun
AU - Newman, Sally J.
AU - Schlaak, Jörg F.
AU - Watling, Diane
AU - Costa-Pereira, Ana P.
AU - Schaper, Fred
AU - Behrmann, Iris
AU - Sheehan, Kathleen C.F.
AU - Schreiber, Robert D.
AU - Horn, Friedemann
AU - Heinrich, Peter C.
AU - Kerr, Ian M.
PY - 2001/10/1
Y1 - 2001/10/1
N2 - 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)-γ receptor, efficiently mediates an IFN-γ-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-γ-like response, but less efficiently. The IFNGR1 signal-transducing subunit of the IFN-γ 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-γ-like response through the chimeric receptors, nor does it mediate an IFN-γ-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.
AB - 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)-γ receptor, efficiently mediates an IFN-γ-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-γ-like response, but less efficiently. The IFNGR1 signal-transducing subunit of the IFN-γ 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-γ-like response through the chimeric receptors, nor does it mediate an IFN-γ-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.
KW - Cytokine
KW - Interferon
KW - Modular signalling
KW - Receptor cross phosphorylation
UR - http://www.scopus.com/inward/record.url?scp=17944381636&partnerID=8YFLogxK
U2 - 10.1093/emboj/20.19.5431
DO - 10.1093/emboj/20.19.5431
M3 - Article
C2 - 11574475
AN - SCOPUS:17944381636
SN - 0261-4189
VL - 20
SP - 5431
EP - 5442
JO - EMBO Journal
JF - EMBO Journal
IS - 19
ER -