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Phosphorylation of STAT2 on serine-734 negatively regulates the IFN-alpha-induced antiviral response
J Cell Sci. 2016 Nov 15;129(22) :4190-4199
PMID: 27802159 PMCID: PMC6518330 URL: https://www.ncbi.nlm.nih.gov/pubmed/27802159
AbstractSerine phosphorylation of STAT proteins is an important post-translational modification event that, in addition to tyrosine phosphorylation, is required for strong transcriptional activity. However, we recently showed that phosphorylation of STAT2 on S287 induced by type I interferons (IFN-alpha and IFN-beta), evoked the opposite effect. S287-STAT2 phosphorylation inhibited the biological effects of IFN-alpha. We now report the identification and characterization of S734 on the C-terminal transactivation domain of STAT2 as a new phosphorylation site that can be induced by type I IFNs. IFN-alpha-induced S734-STAT2 phosphorylation displayed different kinetics to that of tyrosine phosphorylation. S734-STAT2 phosphorylation was dependent on STAT2 tyrosine phosphorylation and JAK1 kinase activity. Mutation of S734-STAT2 to alanine (S734A) enhanced IFN-alpha-driven antiviral responses compared to those driven by wild-type STAT2. Furthermore, DNA microarray analysis demonstrated that a small subset of type I IFN stimulated genes (ISGs) was induced more by IFNalpha in cells expressing S734A-STAT2 when compared to wild-type STAT2. Taken together, these studies identify phosphorylation of S734-STAT2 as a new regulatory mechanism that negatively controls the type I IFN-antiviral response by limiting the expression of a select subset of antiviral ISGs.
Notes1477-9137 Steen, Hakan C Kotredes, Kevin P Nogusa, Shoko Harris, Michele Y Balachandran, Siddharth Gamero, Ana M ORCID: http://orcid.org/0000-0001-7843-1415 Journal Article England J Cell Sci. 2016 Nov 15;129(22):4190-4199. Epub 2016 Oct 19.