Abstract
All Type I interferons (IFNalpha, IFNbeta, IFNomega) 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, IFNbeta selectively induces the association of the alpha subunit of the Type I IFNR with p100, a tyrosyl phosphoprotein, to transduce IFNbeta-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 (betaL subunit) of the Type I IFNR. This was also confirmed in experiments with mouse L-929 cells transfected with truncated forms of betaL. Thus, IFNbeta stimulation of human cells or mouse L-929 transfectants expressing the human alpha and betaL subunits, selectively induces the formation of a signaling complex containing the alpha and betaL subunits of the receptor. The IFNbeta-regulated interaction of the alpha and betaL 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.
Highlights
All Type I interferons (IFN␣, IFN, IFN) 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
It is well established that the Type I IFN receptor has a multichain structure [3,4,5,6], composed of the 110 –130-kDa ␣ subunit [6] and the  subunit [7,8,9]
Previous studies have shown that expression of the human ␣ and L subunits of the Type I IFNR in mouse cells is sufficient for activation of Stat proteins by human IFN␣ and reconstitution of the antiviral effects of human IFN␣ and IFN [7]
Summary
All Type I interferons (IFN␣, IFN, IFN) 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. Events in Type I IFN signaling are the tyrosine phosphorylation of the ␣ (10 –13) and  [11] subunits of the Type I IFNR and the activation of the receptor-associated Tyk-2 and Jak-1 kinases (14 –18).
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