Interferons induce tyrosine phosphorylation of the eIF2 alpha kinase PKR through activation of Jak1 and Tyk2.

Qiaozhu Su, Shuo Wang, Antonis E. Koromilas

Research output: Contribution to journalArticle

Abstract

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 eIF2a 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 eIF2a phosphorylation.
Original languageEnglish
Article numberPMID: 17290288
Pages (from-to)265-270
Number of pages6
JournalEMBO Reports
Volume8
Issue number3
DOIs
Publication statusPublished - 09 Feb 2007

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