Trif-related adapter molecule is phosphorylated by PKCε during Toll-like receptor 4 signaling
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- Anne F. McGettrick
- *School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland;
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- Elizabeth K. Brint
- *School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland;
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- Eva M. Palsson-McDermott
- *School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland;
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- Daniel C. Rowe
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01604; and
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- Douglas T. Golenbock
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01604; and
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- Nicholas J. Gay
- Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom
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- Katherine A. Fitzgerald
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01604; and
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- Luke A. J. O'Neill
- *School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland;
説明
<jats:p>PKCε has been shown to play a key role in the effect of the Gram-negative bacterial product LPS; however, the target for PKCε in LPS signaling is unknown. LPS signaling is mediated by Toll-like receptor 4, which uses four adapter proteins, MyD88, MyD88 adapter-like (Mal), Toll/IL-1R domain-containing adapter inducing IFN-β (Trif), and Trif-related adapter molecule (TRAM). Here we show that TRAM is transiently phosphorylated by PKCε on serine-16 in an LPS-dependent manner. Activation of IFN regulatory factor 3 and induction of the chemokine RANTES, which are both TRAM-dependent, were attenuated in PKCε-deficient cells. TRAMS16A is inactive when overexpressed and is attenuated in its ability to reconstitute signaling in TRAM-deficient cells. We have therefore uncovered a key process in Toll-like receptor 4 signaling, identifying TRAM as the target for PKCε.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 103 (24), 9196-9201, 2006-06-13
Proceedings of the National Academy of Sciences