TY - JOUR
T1 - Mitogen-activated protein kinase-activated kinase RSK2 plays a role in innate immune responses to influenza virus infection
AU - Kakugawa, Satoshi
AU - Shimojima, Masayuki
AU - Goto, Hideo
AU - Horimoto, Taisuke
AU - Oshimori, Naoki
AU - Neumann, Gabriele
AU - Yamamoto, Tadashi
AU - Kawaoka, Yoshihiro
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
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U2 - 10.1128/JVI.02416-08
DO - 10.1128/JVI.02416-08
M3 - Article
C2 - 19129453
AN - SCOPUS:62749090546
SN - 0022-538X
VL - 83
SP - 2510
EP - 2517
JO - Journal of virology
JF - Journal of virology
IS - 6
ER -