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Interferons induce tyrosine phosphorylation of the eIF2α kinase PKR through activation of Jak1 and Tyk2
Author(s) -
Su Qiaozhu,
Wang Shuo,
Baltzis Dionissios,
Qu LiKe,
Raven Jennifer F,
Li Suiyang,
Wong Andrew HoiTao,
Koromilas Antonis E
Publication year - 2007
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.7400891
Subject(s) - protein kinase r , phosphorylation , tyrosine phosphorylation , biology , microbiology and biotechnology , protein tyrosine phosphatase , eif 2 kinase , eif2 , interferon , tyrosine , phosphorylation cascade , protein kinase a , protein phosphorylation , translation (biology) , biochemistry , mitogen activated protein kinase kinase , cyclin dependent kinase 2 , messenger rna , virology , gene
The interferon (IFN)‐inducible, double‐stranded RNA activated protein kinase (PKR) is a dual‐specificity kinase, which has an essential role in the regulation of protein synthesis by phosphorylating the translation eukaryotic initiation factor 2 (eIF2). Here, we show the tyrosine (Tyr) phosphorylation of PKR in response to type I or type II IFNs. We show that PKR physically interacts with either Jak1 or Tyk2 in unstimulated cells and that these interactions are increased in IFN‐treated cells. We also show that PKR acts as a substrate of activated Jaks, and is phosphorylated at Tyr 101 and Tyr 293 both in vitro and in vivo . Moreover, we provide strong evidence that both the induction of eIF2α phosphorylation and inhibition of protein synthesis by IFN are impaired in cells lacking Jak1 or Tyk2, which corresponds to a lack of induction of PKR tyrosine phosphorylation. We conclude that PKR tyrosine phosphorylation provides an important link between IFN signalling and translational control through the regulation of eIF2α phosphorylation.