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. 2022 Jan 13;58(1):121. doi: 10.3390/medicina58010121

Figure 2.

Figure 2

Upon binding to their receptors, IFNs induce the activation of the JAK/STAT signaling pathway. Type I IFNs first bind to the extracellular part of type I IFN heterodimeric receptor complex IFN-α/β R1 and IFN-α/β R2. Receptor engagement subsequently activates IFN-alpha/beta R1 and IFN-α/β R2, resulting in conformational changes in their associated intracellular tyrosine residues Tyk2 and JAK1 protein tyrosine. Both type I and III IFNs use JAK1 for their signaling. Apart from IFNL-R1 receptor, type III IFNs also use IL-10 receptor beta (IL-10R2) receptor complex. Following JAK activation, STAT1/STAT2 are recruited and activated, which leads to their dimerization and binding to IRF9 and ISRE, forming the ISGF3 complex. Upon JAK activation, STAT1 homodimer complex are also formed, which translocate into the nucleus, and drives ISG production. STAT1 homodimers interact with GAS to induce a pro-inflammatory response. GAS, gamma activated sequences; IFN, interferon; IRF9, interferon regulatory factor 9; ISGF3, interferon stimulated gene factor 3; ISRE, interferon-stimulated regulatory element, JAK, Janus kinase; STAT, signal transducer and activator of transcription; TYK2, tyrosine Kinase 2. Figure created with BioRender.com (accessed on 10 October 2021).