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Papers In Press, published online ahead of print May 27, 2004
Ludwig Institute for Cancer Research, Brussels B-1200
Corresponding Author: renauld{at}licr.ucl.ac.be
IFN-1, -2 and -3 are the latest members of the class II cytokine family and were shown to have antiviral activity. Their receptor is composed of two chains, IL-28R/LICR2 and IL-10Rß, and mediates the tyrosine phosphorylation of STAT1, STAT2, STAT3 and STAT5. Here, we show that activation of this receptor by IFN-1 can also inhibit cell proliferation and induce STAT4 phosphorylation, further extending functional similarities with type I IFNs. We used IL-28R/LICR2 mutated receptors to identify the tyrosines required for STAT activation, as well as anti-proliferative and antiviral activities. We found that IFN-1-induced STAT2 tyrosine phosphorylation is mediated through tyrosines 343 and 517 of the receptor, which showed some similarities with tyrosines from type I IFN receptors involved in STAT2 activation. These 2 tyrosines were also responsible for antiviral and antiproliferative activities of IFN-1. By contrast, STAT4 phosphorylation (and to some extent STAT3 activation) was independent from IL-28R/LICR2 tyrosine residues. Taken together, these observations extend the functional similarities between IFN-s and type I IFNs, and shed some new light on the mechanisms of activation of STAT2 and STAT4 by these cytokines.
J. Biol. Chem, 10.1074/jbc.M404789200
Submitted on April 29, 2004
Revised on May 26, 2004
Accepted on May 27, 2004
Role of the Interleukin-28 Receptor tyrosine residues for antiviral and antiproliferative activity of IL-29/IFN-
1 : Similarities with type I Interferon signalling
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