IFNAR2 (E7Z4M) Rabbit mAb

Interferon alpha/beta receptor 2 (IFNAR2) is one of the two protein subunits that comprise the type I interferon (IFN-I) surface receptor. IFNAR2 is a class II helical cytokine receptor with an ectodomain composed of two fibronectin type III-like subdomains, D1 and D2, and an unstructured intracellular domain (ICD) (1,2). IFNAR2 is expressed on most nucleated cells (3). IFN-Is bind the IFN receptor, leading to the dimerization of IFNAR2 and IFNAR1 subunits, and the activation of Janus family kinase (JAK) and signal transducer and activator of transcription (STAT) signaling pathways (4,5). JAK1 is associated with IFNAR2, and STAT1 and STAT2 are constitutively bound to the intracellular domain (ICD) of IFNAR2 (6,7). The formation of the transcription factor IFN-stimulated gene factor 3 (ISGF3), which is a complex made up of the pSTAT1-pSTAT2 heterodimer and interferon regulatory factor 9 (IRF-9), leads to the transcription of interferon-stimulated genes (ISGs) (8). IFN-I subtypes have differential binding affinity toward IFNAR2, contributing to differences in response potency (9). In contrast, IFN-αs all bind IFNAR1 with a low affinity and only IFN-β binds IFNAR1 with a relatively higher affinity (10). IFN-I signaling mediates various cellular responses, including antiviral responses, immunomodulatory responses, and antiproliferative effects (3). In the tumor microenvironment (TME), the presence of IFN-I signaling is associated with “hot” tumors in which key effector immune cells are present and is predictive of therapeutic response, whereas suppressed IFN-I signaling in the TME is associated with tumor progression and poorer outcomes (11,12). IFN-I signaling is being investigated as a therapeutic target for cancer, autoimmunity, sepsis, and viral infection (13,14). 1.Bazan, J.F. (1990) Proc Natl Acad Sci U S A 87, 6934-8. 2.Novick, D. et al. (1994) Cell 77, 391-400. 3.Platanias, L.C. (2005) Nat Rev Immunol 5, 375-86. 4.Cohen, B. et al. (1995) Mol Cell Biol 15, 4208-14. 5.Shuai, K. et al. (1992) Science 258, 1808-12. 6.Saleh, A.Z. et al. (2002) Biochemistry 41, 11261-8. 7.Arimoto, K.I. et al. (2017) Nat Struct Mol Biol 24, 279-289. 8.Schreiber, G. (2017) J Biol Chem 292, 7285-7294. 9.Lavoie, T.B. et al. (2011) Cytokine 56, 282-9. 10.Lamken, P. et al. (2004) J Mol Biol 341, 303-18. 11.Katlinski, K.V. et al. (2017) Cancer Cell 31, 194-207. 12.Katlinskaya, Y.V. et al. (2016) Cell Rep 15, 171-180. 13.Trinchieri, G. (2010) J Exp Med 207, 2053-63. 14.Schreiber, G. (2020) Front Immunol 11, 595739.