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Phosphorylation of the Stat1 transactivating domain is required for the response to type I interferons
Author(s) -
Pilz Andreas,
Ramsauer Katrin,
Heidari Hamid,
Leitges Michael,
Kovarik Pavel,
Decker Thomas
Publication year - 2003
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.embor802
Subject(s) - stat1 , stat2 , phosphorylation , transcription factor , transcription (linguistics) , stat protein , chemistry , interferon , microbiology and biotechnology , biology , cancer research , virology , gene , biochemistry , stat3 , linguistics , philosophy
Stat1 (signal transducer and activator of transcription 1) regulates transcription in response to the type I interferons IFN‐α and IFN‐β, either in its dimerized form or as a subunit of the interferon‐stimulated gene factor 3 (Isgf3) complex (consisting of Stat1, Stat2 and interferon‐regulating factor 9). Full‐length Stat1‐α and the splice variant Stat1‐β, which lacks the carboxyl terminus and the Ser727 phosphorylation site, are found in all cell types. IFN‐induced phosphorylation of Stat1‐α on Ser727 occurs in the absence of the candidate kinase, protein kinase C‐δ. When expressed in Stat1‐deficient cells, Stat1‐β and a Stat1‐S727A mutant both restored the formation of Stat1 dimers and of the Isgf3 complex on treatment with IFN‐β. By contrast, only Stat1‐α restored the ability of IFN‐β to induce high levels of transcription from target genes of Stat1 dimers and Isgf3 and to induce an antiviral state. Our data suggest an important contribution of the Stat1 C terminus and its phosphorylation at Ser727 to the transcriptional activities of the Stat1 dimer and the Isgf3 complex.