title: Mitogen-activated protein kinase-activated kinase RSK2 plays a role in innate immune responses to influenza virus infection.
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-kappaB- 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.
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kakugawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimojima
authors.forename: Hideo
authors.initials: H
authors.lastname: Goto
authors.forename: Taisuke
authors.initials: T
authors.lastname: Horimoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Oshimori
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neumann
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D055785:Gene Knockdown Techniques; D006801:Humans; D007113:Immunity, Innate; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D007372:Interferons / Q000096:biosynthesis; D008954:Models, Biological; D052003:NF-kappa B p52 Subunit / Q000096:biosynthesis; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000502:physiology*
chemical_list: D052003:NF-kappa B p52 Subunit; D007372:Interferons; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3