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• W2049004753 startingPage "655" @default.
• W2049004753 abstract "Type I interferons (IFNs) are a family of pleiotropic cytokines with antiviral, antiproliferative, and immunomodulatory properties. The type I IFN family consists of 12 IFN-alpha subtypes, IFN-beta, and IFN-omega. Cells lacking the receptor-associated protein kinase Tyk2 (U1A) are responsive only to IFN-beta and partially to IFN-alpha8. We constructed a series of IFN-alpha2/alpha8 hybrids and mutants and identified the region within IFN-alpha8 responsible for its activity in Tyk2-deficient cells. The same domain mediates the interactions between IFN and IFN-alpha receptor (IFNAR) in Tyk2-complemented and Tyk2-deficient cells (U1A). The presence or absence of Tyk2 altered the inhibitory effects of anti-IFNAR antibodies, suggesting that the IFN-alpha binding domain on IFNAR is altered by the presence of Tyk2. The activity of IFN-beta was not significantly affected by the deletion of Tyk2, and, surprisingly, one of our IFN-alpha2/alpha8 hybrids (IFN-alpha288) behaved like IFN-beta in a number of assays that distinguish IFN-alphas from IFN-beta. This suggests that this hybrid mimics the interactions of IFN-beta with the receptor and also suggests the existence of a distinct binding site(s) on IFNAR for IFN-beta and some hybrid IFN-alphas." @default.
• W2049004753 created "2016-06-24" @default.
• W2049004753 creator A5018352341 @default.
• W2049004753 creator A5065033982 @default.
• W2049004753 date "2003-11-01" @default.
• W2049004753 modified "2023-09-27" @default.
• W2049004753 title "Activity of Hybrid Type I Interferons in Cells Lacking Tyk2: A Common Region of IFN-<i>α</i>8 Induces a Response, but IFN-<i>α</i>2/8 Hybrids Can Behave Like IFN-<i>β</i>" @default.
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• W2049004753 doi "https://doi.org/10.1089/107999003322558791" @default.
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