Differences in interferon α and β signaling: Interferon β selectively induces the interaction of the α and β(L) subunits of the type I interferon receptor

All Type I interferons (IFNα, IFNβ, IFNω) bind to the Type I IFN receptor (IFNR) and elicit a common set of signaling events, including activation of the Jak/Stat and IRS pathways. However, IFNβ selectively induces the association of the α subunit of the Type I IFNR with p100, a tyrosyl phosphoprotein, to transduce IFNβ-specific signals. Using antibodies raised against the different components of the Type I IFNR, we identified p100 as the long form of the β subunit (β(L) subunit) of the Type I IFNR. This was also confirmed in experiments with mouse L-929 cells transfected with truncated forms of β(L). Thus, IFNβ stimulation of human cells or mouse L-929 transfectants expressing the human α and β(L) subunits, selectively induces the formation of a signaling complex containing the α and β(L) subunits of the receptor. The IFNβ-regulated interaction of the α and β(L) chains is rapid and transient and follows a similar time course with the tyrosine phosphorylation of these receptor components. These data demonstrate that the signaling specificity for different Type I IFNs is established early in the signaling cascade, at the receptor level, and results from distinct interactions between components of the Type I IFNR.