FIGURE 5.

IFN signaling cascades. The IFN type I (IFN-I) and III (IFN-III) bind to their cognate receptors, IFNα receptors (IFNAR) and IFNλ receptors (IFNLR), respectively, on the cell surface, leading to the activation of Janus kinase 1 (JAK-1) and tyrosine kinase 2 (TYK-2). As a result, activated signal transducers and activators of transcription 1 and 2 (STAT1 and STAT2, respectively) are phosphorylated and bind to IFN regulatory factor 9 (IRF9) to form ISGF3, which translocates to the nucleus to induce the expression of ISGs. The IFN type II (IFN-II) signaling cascade is triggered when IFNγ binds to IFNγ receptor (IFNGR) and activates JAK1 and Janus kinase 2 (JAK2). Consequently, STAT1 molecules are phosphorylated and localized to the nucleus to transactivate ISG expression. Adapted with permission from Alandijany (2018).