Role of p38α Map Kinase in Type I Interferon Signaling

Yongzhong Li, Antonella Sassano, Beata Majchrzak, Dilip K. Deb, David E. Levy, Matthias Gaestel, Angel R. Nebreda, Eleanor N. Fish, Leonidas C. Platanias*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Multiple signaling pathways are activated during engagement of the Type I interferon (IFN) receptor to mediate biological responses, including the Jak-Stat and Rac1/p38 Map kinase signaling cascades. In the present study we sought to determine the functional relevance of the p38α isoform in IFN signaling, using cells from mouse embryos with targeted disruption of the p38α gene. Our data demonstrate that p38α activation is essential for Type I IFN-dependent transcriptional regulation via ISRE or GAS elements. On the other hand, the function of p38α is not required for IFN-dependent Ser727 or Tyr701 phosphorylation of Stat1 and does not impact on the formation of ISGF3 or SIF nuclear binding complexes. In efforts to identify downstream effectors of p38 that may mediate IFN-dependent transcriptional responses, we found that IFNα activates the kinase Msk1, a known regulator of histone phosphorylation and chromatin remodeling. In other studies, we demonstrate that Type I IFN-dependent activation of the kinases MapKapK-2 and MapKapK-3 is defective in the absence of p38α, while Type I IFN-dependent antiviral properties are decreased in cells with targeted disruption of the MapKapK-2 gene. Altogether, our data establish that the p38α Map kinase pathway regulates activation of downstream effectors that participate in the induction of IFN-dependent gene transcription, to mediate IFN-responses.

Original languageEnglish (US)
Pages (from-to)970-979
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number2
DOIs
StatePublished - Jan 9 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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