Open AccessMitogen-Activated Protein Kinase-Activated Kinase RSK2 Plays a Role in Innate Immune Responses to Influenza Virus Infection
Author(s) -
Satoshi Kakugawa,
Masayuki Shimojima,
Hideo Goto,
Taisuke Horimoto,
Naoki Oshimori,
Gabriele Neumann,
Tadashi Yamamoto,
Yoshihiro Kawaoka
Publication year - 2009
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.02416-08
Subject(s) - biology , protein kinase r , innate immune system , protein kinase a , ribosomal s6 kinase , microbiology and biotechnology , gene knockdown , influenza a virus , mitogen activated protein kinase kinase , signal transduction , virology , immune system , kinase , virus , immunology , p70 s6 kinase 1 , apoptosis , biochemistry , pi3k/akt/mtor pathway
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.