IFNA/B:IFNAR2:JAK1:STAT2 IFNAR2:JAK1:STAT2 IFN alpha/beta binds to IFNAR2 Authored: Garapati, P V, 2010-07-07 Edited: Garapati, P V, 2010-07-07 Pubmed10395669 Pubmed11786546 Pubmed12842042 Pubmed15312780 Pubmed15778442 Pubmed17969444 Pubmed8156998 Pubmed9121453 Pubmed9334213 Reactome Database ID Release 43909720 Reactome, http://www.reactome.org ReactomeREACT_25100 Reviewed: Abdul-Sater, AA, Schindler, C, 2010-08-17 The ligand IFNalpha/beta (IFNA/B), interacts independently with the two interferon receptor subunits. Based on detailed binding studies with the extracellular domains of the receptor subunits tethered onto solid-supported membranes, a two-step binding mechanism was experimentally confirmed, where the ligand binds first to one of the receptor subunits and then recruits the second subunit (Gavutis et al. 2005). The efficiency of recruitment of the IFNA receptor subunits by the IFN ligand depends on the absolute and relative concentration of the receptor subunits. <br>IFNAR2 chain constitutively associates with JAK1 kinase in its cytoplasmic domain. In addition IFNAR2 also binds STAT2 in a constitutive manner and this interaction is biochemically different from the interaction of STAT2 with phosphorylated IFNAR1. Although this interaction facilitates the recruitment of STAT2 to the receptors, the biological significance of this constitutive STAT2 interaction to IFNAR2 remains unclear (Nguyen et al, 2002). IFNAR2 not only associates with STAT2, but also with STAT1 and this binding of STAT1 to IFNAR2 depends on the presence of STAT2 but not vice versa.<br>IFNA/B may first bind to the high-affinity subunit IFNAR2 and subsequently recruit IFNAR1 in a transient fashion (Lamken et al. 2004). Different type I IFNs interact differently with the two IFNA receptor (IFNAR) subunits, IFNB generates a more stable signaling complex than IFNA subtypes. The interaction between IFNalpha2 (IFNA2) and IFNAR2 has an affinity in the nM range, whereas the affinity of the interaction with INFB is about tenfold tighter. IFNA/B