Tyrosine phosphorylation acts as a molecular switch to full-scale activation of the eIF2alpha RNA-dependent protein kinase

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

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

Abstract

Phosphorylation of the alpha-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 eIF2alpha 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 eIF2alpha 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 eIF2alpha kinase PKR.

Original languageEnglish
Article numberPMID: 16373505
Pages (from-to)63-68
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number1
DOIs
Publication statusPublished - 03 Jan 2006
Externally publishedYes

Keywords

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Enzyme Activation/physiology
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Mice
  • Mice, Knockout
  • Mutation/genetics
  • Phosphorylation
  • Protein Biosynthesis/genetics
  • Tyrosine/metabolism
  • eIF-2 Kinase/genetics

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