Tyrosine phosphorylation acts as a molecular switch to full-scale activation of the eIF2α RNA-dependent protein kinase

Qiaozhu Su, Shuo Wang, Dionissios Baltzis, Li Ke Qu, Andrew Hoi Tao Wong, Antonis E. Koromilas

Research output: Contribution to journalArticle

60 Scopus citations


Phosphorylation of the α-subunit of translation eukaryotic initiation factor-2 (eIF2) leads to the inhibition of protein synthesis in response to diverse conditions of stress. Serine/threonine RNA-dependent protein kinase (PKR) is an eIF2α kinase family member induced by type I IFN and activated in response to dsRNA or virus infection. Herein, we demonstrate that human PKR is a dual specificity kinase phosphorylated at Y101, Y162 and Y293 in vitro and in vivo. Site-specific tyrosine phosphorylation is essential for efficient dsRNA-binding, dimerization, kinase activation and eIF2α phosphorylation of PKR. Biologically, tyrosine phosphorylation of PKR mediates the antiviral and antiproliferative properties of the kinase through its ability to control translation. Our data demonstrate an important role of tyrosine phosphorylation in biochemical and biological processes caused or mediated by the activation of the eIF2α kinase PKR.

Original languageEnglish (US)
Pages (from-to)63-68
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number1
StatePublished - Jan 3 2006



  • Cell proliferation
  • Protein phosphorylation
  • Translational control
  • Virus infection

ASJC Scopus subject areas

  • General

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