HCV-induced PKR activation is stimulated by the mitogen- and stress-activated protein kinase MSK2

Ju Il Kang, Byung Yoon Ahn

    Research output: Contribution to journalArticlepeer-review

    4 Citations (Scopus)

    Abstract

    The replication of viral nucleic acids triggers cellular antiviral responses. The double-stranded RNA (dsRNA)-activated protein kinase (PKR) plays a key role in this antiviral response. We have recently reported that JFH-1 HCV replication in Huh-7 cells triggers PKR activation. Here we show that the HCV-induced PKR activation is further stimulated by the mitogen- and stress-activated protein kinase 2 (MSK2), a member of the 90. kDa ribosomal S6 kinase (RSK) family that has emerged as an important downstream effector of ERK and p38 MAPK signaling pathways. We show that MSK2 binds PKR and stimulates PKR phosphorylation, whereas the closely related MSK1 and RSK2 have no effect. Our data further indicate that MSK2 functions as an adaptor in mediating PKR activation, apparently independent of its catalytic activity. These results suggest that, in addition to viral dsRNA, stress signaling contributes to the regulation of cellular antiviral response.

    Original languageEnglish
    Pages (from-to)248-253
    Number of pages6
    JournalBiochemical and biophysical research communications
    Volume407
    Issue number1
    DOIs
    Publication statusPublished - 2011 Apr 1

    Bibliographical note

    Funding Information:
    We thank Dr. T. Wakita for kindly providing us with pJFH1 and Dr. J.H. Yoon for the generous gift of MSK1 plasmid. This work was supported by the Basic Science Research Grant ( #2010-0015980 ) from the National Research Foundation of Korea . J.I. Kang was supported by the BK21 Fellowship from the Ministry of Education, Science & Technology of Korea .

    Keywords

    • DsRNA signaling
    • HCV
    • IFN
    • PKR
    • RSK

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

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