IFNAR2

IFNAR2 (interferon alpha and beta receptor subunit 2) is a core component of the type I interferon receptor complex and associates with IFNAR1 to mediate cellular responses to interferon-α and interferon-β ligands^[1][2]. Upon ligand engagement, IFNAR2 functions as the principal signaling subunit linked to JAK1, enabling receptor complex assembly and activation of the JAK-STAT pathway, which drives phosphorylation of STAT1 and STAT2 and subsequent transcription of interferon-stimulated genes involved in antiviral and immune regulation^[1][2][3]. Mechanistically, formation of the IFN-IFNAR1-IFNAR2 signaling complex promotes cross-activation of receptor-associated kinases and efficient propagation of type I interferon signaling across diverse cell types^[2][3]. In disease contexts, impaired IFNAR2-mediated signaling has been associated with altered antiviral immunity, while genetic variation and expression differences in IFNAR2 have been linked to severe viral infections, including COVID-19, highlighting its importance in host defense pathways^[4]. Compared with the related receptor subunit IFNAR1, IFNAR2 exhibits distinctive isoform diversity generated by alternative splicing, producing signaling-competent membrane isoforms as well as soluble or truncated isoforms with limited or inhibitory signaling capacity^[5]. This isoform-specific biology provides an important experimental framework for dissecting receptor activation, signal strength, and interferon responsiveness in cellular models^[5]. For research applications, recombinant soluble IFNAR2 and endogenous soluble IFNAR2 have been used to investigate modulation of type I interferon activity and receptor-dependent antiviral responses, supporting their utility as mechanistic tools in interferon signaling studies^[6].