Mitogen-activated protein kinase-activated kinase RSK2 plays a role in innate immune responses to influenza virus infection

Satoshi Kakugawa, Masayuki Shimojima, Hideo Goto, Taisuke Horimoto, Naoki Oshimori, Gabriele Neumann, Tadashi Yamamoto, Yoshihiro Kawaoka

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Viral infections induce signaling pathways in mammalian cells that stimulate innate immune responses and affect cellular processes, such as apoptosis, mitosis, and differentiation. Here, we report that the ribosomal protein S6 kinase alpha 3 (RSK2), which is activated through the "classical" mitogen-activated protein kinase pathway, plays a role in innate immune responses to influenza virus infection. RSK2 functions in the regulation of cell growth and differentiation but was not known to play a role in the cellular antiviral response. We have found that knockdown of RSK2 enhanced viral polymerase activity and growth of influenza viruses. Influenza virus infection stimulates NK-κB- and beta interferon-dependent promoters. This stimulation was reduced in RSK2 knockdown cells, suggesting that RSK2 executes its effect through innate immune response pathways. Furthermore, RSK2 knockdown suppressed influenza virus-induced phosphorylation of the double-stranded RNA-activated protein kinase PKR, a known antiviral protein. These findings establish a role for RSK2 in the cellular antiviral response.

Original languageEnglish (US)
Pages (from-to)2510-2517
Number of pages8
JournalJournal of Virology
Volume83
Issue number6
DOIs
StatePublished - Mar 2009
Externally publishedYes

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Mitogen-Activated Protein Kinase Kinases
Virus Diseases
Orthomyxoviridae
mitogen-activated protein kinase
Innate Immunity
phosphotransferases (kinases)
eIF-2 Kinase
Antiviral Agents
infection
protein kinases
antiviral proteins
interferon-beta
Double-Stranded RNA
Interferon-beta
ribosomal proteins
double-stranded RNA
Growth
Mitogen-Activated Protein Kinases
Mitosis
cell differentiation

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Mitogen-activated protein kinase-activated kinase RSK2 plays a role in innate immune responses to influenza virus infection. / Kakugawa, Satoshi; Shimojima, Masayuki; Goto, Hideo; Horimoto, Taisuke; Oshimori, Naoki; Neumann, Gabriele; Yamamoto, Tadashi; Kawaoka, Yoshihiro.

In: Journal of Virology, Vol. 83, No. 6, 03.2009, p. 2510-2517.

Research output: Contribution to journalArticle

Kakugawa, S, Shimojima, M, Goto, H, Horimoto, T, Oshimori, N, Neumann, G, Yamamoto, T & Kawaoka, Y 2009, 'Mitogen-activated protein kinase-activated kinase RSK2 plays a role in innate immune responses to influenza virus infection', Journal of Virology, vol. 83, no. 6, pp. 2510-2517. https://doi.org/10.1128/JVI.02416-08
Kakugawa, Satoshi ; Shimojima, Masayuki ; Goto, Hideo ; Horimoto, Taisuke ; Oshimori, Naoki ; Neumann, Gabriele ; Yamamoto, Tadashi ; Kawaoka, Yoshihiro. / Mitogen-activated protein kinase-activated kinase RSK2 plays a role in innate immune responses to influenza virus infection. In: Journal of Virology. 2009 ; Vol. 83, No. 6. pp. 2510-2517.
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