Differences in interferon alpha and beta signaling - Interferon beta selectively induces the interaction of the alpha and beta(L) subunits of the Type I interferon receptor
All Type I interferons (IFN alpha, IFN beta, IFN omega) 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, IFN beta selectively induces the association of the alpha subunit of the Type I IFNR with p100, a tyrosyl phosphoprotein, to transduce IFN beta-specific signals. Using antibodies raised against the different components of the Type I IFNR, we identified p100 as the long form of the beta subunit (beta(L) subunit) of the Type I IFNR, This was also confirmed in experiments with mouse L-929 cells transfected with truncated forms of beta(L). Thus, IFN beta stimulation of human cells or mouse L-929 transfectants expressing the human alpha and beta(L) subunits, selectively induces the formation of a signaling complex containing the alpha and beta(L) subunits of the receptor, The IFN beta-regulated interaction of the alpha and beta(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.