Interferons

Interferons are endogenously produced proteins that regulate the immune response. They are multifunctional and have antiviral, cell regulatory and antitumour properties.

Keywords: receptors; signal transduction; gene activation

Figure 1. Type I and type II IFN receptors and the molecules involved in signal transduction. Binding of the monomeric form of the type I IFN (a) and the asymmetrical heterodimer of IFN (b) to their respective receptors results in activation of a tyrosine phosphorylation cascade involving the Janus kinases (Tyk2 and JAK2 for type I IFNs; JAK1 and JAK2 for IFN). Phosphorylation of the STAT transcription factors results in the formation of a heterodimer consisting of STAT 1 and STAT2 for the type I IFN, or a homodimer of STAT1 for IFN.
Figure 2. Proposed model for ligand (IFN) binding to receptor and translocation of STAT transcription factors to the nucleus. Data demonstrate that binding of IFN via the C-terminus to the cytoplasmic domain of the receptor (IFNR–cyto) enhances Janus kinase (JAK) binding. This, in turn, causes signal transducer and activator of transcription (STAT) binding. IFN provides the nuclear localization sequence (NLS) for translocation to the nucleus, none of the other participants have been shown to possess an NLS. Data suggest that the chain of the receptor does not undergo nuclear translocation. , importin ; , importin ; GAS, -activated sequence; GTP, guanosine triphosphate.
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 References
    Domanski P and Colamonici OR (1996) The type-I interferon receptor: the long and short of it. Cytokine and Growth Factor Reviews 7: 143–151.
    Johnson HM, Subramaniam PS, Olsnes S and Jans DA (2004) Trafficking and signalling pathways of nuclear localizing protein ligands and their receptors. Bioassays 26: 993–1004.
    McBride KM, Banninger G, McDonald C and Reich NC (2002) Regulated nuclear import of the STAT1 transcription factor by direct binding of importin-alpha. EMBO Journal 21: 1754–1763.
    Pestka S, Kotenko SV, Muthukumaran G, et al. (1997) The interferon gamma (IFN-gamma) receptor: a paradigm for the multichain cytokine receptor. Cytokine and Growth Factor Reviews 8: 189–206.
    Subramaniam PS, Torres BA and Johnson HM (2001) So many ligands, so few transcription factors: a new paradigm for signalling through the STAT transcription factors. Cytokine 15: 175–187.
 Further Reading
    Baron S and Dianzani F (1994) The interferons: a biological system with therapeutic potential in viral infections. Antiviral Research 24: 97–110.
    Jans DA (1994) Nuclear signalling pathways for polypeptide ligands and their membrane receptors?. FASEB Journal 8: 841–847.
    Johnson HM, Bazer FW, Szente BE and Jarpe MA (1994) How interferons fight disease. Scientific American 270(5): 68–75.
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Johnson, Howard M, Torres, Barbara A, and Subramaniam, Prem S(Sep 2005) Interferons. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003969]