Formation of a uniquely stable type I interferon receptor complex by interferon beta is dependent upon particular interactions between interferon beta and its receptor and independent of tyrosine phosphorylation.
Human type I interferons (IFN) require two receptor chains, IFNAR1 and IFNAR2c for high affinity (pM) binding and biological activity. Our previous studies have shown that the ligand dependent assembly of the type I IFN receptor chains is not identical for all type I IFNs. IFNbeta appears unique in its ability to assemble a stable complex of receptor chains, as demonstrated by the observation that IFNAR2c co-immunoprecipitates with IFNAR1 when cells are stimulated with IFNbeta but not with IFNalpha. The characteristics of such a receptor complex are not well defined nor is it understood if differential signaling events can be mediated by variations in receptor assembly. To further characterize the factors required for formation of such a stable receptor complex we demonstrate using IFN stimulated Daudi cells that (1) IFNAR2c co-immunoprecipitates with IFNAR1 even when tyrosine phosphorylation of receptor chains is blocked with staurosporine, and (2) IFNbeta1b but not IFNalpha2, is present in the immunoprecipitated receptor complex. These results demonstrate that the unique IFNbeta induced assembly of type I IFN receptor chains is independent of receptor tyrosine phosphorylation and the recruitment of additional proteins to the receptor by such events. Furthermore, the presence of IFNbeta1b in the immunoprecipitated IFN receptor complex suggests that IFNbeta interacts and binds differently to the receptor than IFNalpha2. These results suggest that the specific assembly of type I IFN receptor chains is ligand dependent and may represent an early event which leads to the differential biological responses observed among type I IFNs.
Department of Protein Biochemistry, Department of Immunology, Berlex Biosciences, Richmond, California 94804, USA.
D
D
Russell-Harde
T C
TC
Wagner
H D
HD
Perez
E
E
Croze
D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000378:metabolism*; D046911:Macromolecular Substances; D008565:Membrane Proteins; D008954:Models, Biological; D008958:Models, Molecular; D010766:Phosphorylation; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
C507964:IFNAR1 protein, human; D007370:Interferon Type I; D046911:Macromolecular Substances; D008565:Membrane Proteins; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D053633:Receptor, Interferon alpha-beta; D014443:Tyrosine; D016899:Interferon-beta; D000068556:Interferon beta-1a