TAK1 Is a Central Mediator of NOD2 Signaling in Epidermal Cells.

TAK1 Is a Central Mediator of NOD2 Signaling in Epidermal Cells. Research Abstract Details 

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TAK1 Is a Central Mediator of NOD2 Signaling in Epidermal Cells. Abstract Text:

Jae-Young Kim,Emily Omori,Kunihiro Matsumoto,Gabriel ,Jun Ninomiya-Tsuji,Jae-Young Kim,Emily Omori,Kunihiro Matsumoto,Gabriel ,Jun Ninomiya-Tsuji,

Muramyl dipeptide (MDP) is a peptidoglycan moiety derived from commensal and pathogenic bacteria, and a ligand of its intracellular sensor NOD2. Mutations in NOD2 are highly associated with Crohn disease, which is characterized by dysregulated inflammation in the intestine. However, the mechanism linking abnormality of NOD2 signaling and inflammation has yet to be elucidated. Here we show that transforming growth factor beta-activated kinase 1 (TAK1) is an essential intermediate of NOD2 signaling. We found that TAK1 deletion completely abolished MDP-NOD2 signaling, activation of NF-kappaB and MAPKs, and subsequent induction of cytokines/chemokines in keratinocytes. NOD2 and its downstream effector RICK associated with and activated TAK1. TAK1 deficiency also abolished MDP-induced NOD2 expression. Because mice with epidermis-specific deletion of TAK1 develop severe inflammatory conditions, we propose that TAK1 and NOD2 signaling are important for maintaining normal homeostasis of the skin, and its ablation may impair the skin barrier function leading to inflammation.

TAK1 Is a Central Mediator of NOD2 Signaling in Epidermal Cells. Publishing Authors By Initials

JY Kim,E Omori,K Matsumoto,G ,J Ninomiya-Tsuji,JY Kim,E Omori,K Matsumoto,G ,J Ninomiya-Tsuji,

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TAK1 Is a Central Mediator of NOD2 Signaling in Epidermal Cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The Journal of biological chemistry

VOLUME: 283

Page Numbers: 137-44

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 26

MONTH: 10

YEAR: 2007

TAK1 Is a Central Mediator of NOD2 Signaling in Epidermal Cells. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

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Grant and Affiliation Information for TAK1 Is a Central Mediator of NOD2 Signaling in Epidermal Cells.

AFFILIATION: Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina 27695.

Country: United States

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MEDLINETA: J Biol Chem

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