IFNAR

The interferon-α/β receptor (IFNAR) is composed of two subunits, IFNAR1 and IFNAR2, encoding transmembrane polypeptides. Type-I IFNs, interferon α (IFN-α) and interferon β (IFN-β), act through a shared receptor complex, IFNAR. Binding of type-I IFN to IFNAR1 will robustly activate Janus activated kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Aberrant activation of the type-I IFN response results in a spectrum of disorders called interferonopathies.

Type-I IFN response occurs when IFN-α/β binds to their receptor complex, IFNAR. The ligand-receptor complex is phosphorylated, presumably by pre-associated Janus activated kinases (JAKs) namely tyrosine kinase 2 (TYK2) on IFNAR1 and JAK1 on IFNAR2. The phosphorylated receptors are docking sites for signal transducers and activators of transcription (STAT) factors that dimerise and translocate to the nucleus. STATs 1, 2, 3, 4, and 5 are activated by type-I IFNs in many cell types. Other kinases (e.g., mitogen-activated protein kinases) and transcription factors (e.g., nuclear factor-κB) can also be activated in response to type-I IFNs. Multiple pathways and IFN-regulated genes are activated by IFNs, many of which remain unknown.