Tyrosine phosphorylation of the α and β subunits of the type I interferon receptor. Interferon-β selectively induces tyrosine phosphorylation of an α subunit-associated protein

We studied the phosphorylation of the α and β subunits of the Type I interferon (IFN) receptor induced by Type I IFNs in the human U-266 and MOLT- 4 cell lines. Both IFN-α and IFN-β induced tyrosine phosphorylation of the β subunit of the receptor. The Type I IFN-induced tyrosine phosphorylation of the β subunit was rapid and transient, being detectable within 1 min of Type I IFN treatment and gradually diminishing to almost base-line levels by 60 min. All Type I IFNs studied were found to induce tyrosine phosphorylation of the α subunit of the Type I IFN receptor, the p135(tyk2) and JAK-1 tyrosine kinases, and the ISGF3α components. Interestingly, IFN-β, but not IFN-α or IFN-ω, induced tyrosine phosphorylation of an α subunit- associated protein with an apparent molecular mass of ~100 kDa (p100). These data suggest the existence of a common signaling pathway(s) for Type I IFNs involving the α and β subunits of the receptor, the tyrosine kinases p135(tyk2) and JAK-1, and the ISGF3α components. However, differences between the signaling pathways of different Type I IFNs exist, as suggested by tyrosine phosphorylation of an α subunit-associated protein only in response to IFN-β.