Expression of IFN-induced genes ISGF3 binds the ISRE promoter elements in IFN-stimulated genes Formation of p-STAT1 homodimer Translocation of p-STAT1:p-STAT1 dimer to nucleus Interaction of IRF9 with p-STAT2:p-STAT1 Translocation of ISGF3 complex to nucleus IFN alpha/beta binds to IFNAR2 Release of p-STAT2:p-STAT1 dimer Phosphorylation of STAT2 Phosphorylation of STAT1 Phosphorylation of INFAR1 by TYK2 Recruitment of STAT2 to p-IFNAR1 Recruitment of IFNAR1 Activation of JAK kinases PathwayStep7061 PathwayStep7048 PathwayStep7049 PathwayStep7044 PathwayStep7045 PathwayStep7046 PathwayStep7047 PathwayStep7042 PathwayStep7043 PathwayStep7055 PathwayStep7053 PathwayStep7054 PathwayStep7051 PathwayStep7052 PathwayStep7050 Interferon alpha/beta signaling Authored: Garapati, P V, 2010-07-07 Edited: Garapati, P V, 2010-07-07 GENE ONTOLOGYGO:0060337 Pubmed17969444 Pubmed8605876 Pubmed8621447 Pubmed8702790 Reactome Database ID Release 43909733 Reactome, http://www.reactome.org ReactomeREACT_25162 Reviewed: Abdul-Sater, AA, Schindler, C, 2010-08-17 Type I interferons (IFNs) are composed of various genes including IFN alpha (IFNA), beta (IFNB), omega, epsilon, and kappa. In humans the IFNA genes are composed of more than 13 subfamily genes, whereas there is only one IFNB gene. The large family of IFNA/B proteins all bind to a single receptor which is composed of two distinct chains: IFNAR1 and IFNAR2. The IFNA/B stimulation of the IFNA receptor complex leads to the formation of two transcriptional activator complexes: IFNA-activated-factor (AAF), which is a homodimer of STAT1 and IFN-stimulated gene factor 3 (ISGF3), which comprises STAT1, STAT2 and a member of the IRF family, IRF9/P48. AAF mediates activation of the IRF-1 gene by binding to GAS (IFNG-activated site), whereas ISGF3 activates several IFN-inducible genes including IRF3 and IRF7. Regulation of IFNA signaling