Interferon alpha/beta signaling

Stable Identifier
R-HSA-909733
DOI
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Pathway
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Homo sapiens
ReviewStatus
5/5
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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.
Literature References
PubMed ID Title Journal Year
8605876 Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein

Gupta, S, Greenlund, AC, Krolewski, JJ, Yan, H, Schreiber, RD, Schindler, CW, Lim, JT, Krishnan, K

EMBO J 1996
17969444 The receptor of the type I interferon family

Pellegrini, S, Piehler, J, Schreiber, G, Uzé, G

Curr Top Microbiol Immunol 2007
8702790 Interferon-alpha-dependent activation of Tyk2 requires phosphorylation of positive regulatory tyrosines by another kinase

Gauzzi, MC, Pellegrini, S, Velazquez, L, McKendry, R, Fellous, M, Mogensen, KE

J Biol Chem 1996
8621447 Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha

Stark, GR, Darnell JE, Jr, Qureshi, S, Li, X, Leung, S

J Biol Chem 1996
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