Okadaic acid activates the PKR pathway and induces apoptosis through PKR stimulation in MG63 osteoblast-like cells

Tatsuji Haneji, Kanji Hirashima, Jumpei Teramachi, Hiroyuki Morimoto

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Double-stranded RNA-dependent protein kinase (PKR) is one of the players in the cellular antiviral responses and is involved in transcriptional stimulation through activation of NF-κB. Treatment of the human osteosarcoma cell line MG63 with the protein phosphatase inhibitor okadaic acid stimulated the expression and phosphorylation of IκBα, as judged from the results of real-time PCR and western blot analysis. We investigated the functional relationship between PKR and signal transduction of NF-κB by establishing PKR-K/R cells that produced a catalytically inactive mutant of PKR. Phosphorylation of eIF-2α, a substrate of PKR, was not stimulated by okadaic acid in the PKR-K/R cells, whereas okadaic acid induced phosphorylation of eIF-2α in MG63 cells. Phosphorylation of NF-κB in MG63 cells was stimulated by okadaic acid; however, okadaic acid did not induce phosphorylation of NF-κB in the PKR-K/R cells. Finally, okadaic acid-induced apoptosis was inhibited in the PKR-K/R cells. Our results suggest that okadaic acid-induced phosphorylation of IκBα was mediated by PKR kinase activity, thus, indicating the involvement of this kinase in the control mechanism governing the activation of NF-κB and induction of apoptosis.

Original languageEnglish
Pages (from-to)1904-1910
Number of pages7
JournalInternational journal of oncology
Volume42
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Dephosphorylation
  • IκBα
  • NF-κB
  • Okadaic acid
  • PKR
  • Phosphorylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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