PubMed Journals: J Biol Chem

  Source:		PMID: 14578350

    		J Biol Chem. 2004 Jan 9;279(2):970-9. Epub
     		2003 Oct 24.

			Role of p38alpha Map kinase in Type I interferon

			Li Y(1), Sassano A, Majchrzak B, Deb DK,
			Levy DE, Gaestel M, Nebreda AR, Fish EN,
			Platanias LC.

			Author Information
			(1) Robert H. Lurie Comprehensive Cancer
			Center, Northwestern University Medical
			School and Lakeside Veterans Administration
			Medical Center, Chicago, Illinois 60611,

			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 p38alpha isoform in IFN
			signaling, using cells from mouse embryos
			with targeted disruption of the p38alpha
			gene. Our data demonstrate that p38alpha
			activation is essential for Type I IFN-dependent
			transcriptional regulation via ISRE or GAS
			elements. On the other hand, the function
			of p38alpha 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
			IFNalpha 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
			p38alpha, 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 p38alpha Map
			kinase pathway regulates activation of downstream
			effectors that participate in the induction
			of IFN-dependent gene transcription, to
			mediate IFN-responses.

			DOI: 10.1074/jbc.M309927200 PMID: 14578350
			[Indexed for MEDLINE]

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