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Trif-related adapter molecule is phosphorylated by protein kinase C epsilon during Toll-like receptor 4 signalling |
MCGETTRICK-DILLON, ANNE; O'NEILL, LUKE ANTHONY JOHN; PALSSON, EVA
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peer-reviewed PKC? has been shown to play a key role in the effect of the Gram-negative bacterial product LPS; however, the target for PKC? 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-? (Trif), and Trif-related adapter molecule (TRAM). Here we show that TRAM is transiently phosphorylated by PKC? 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 PKC?-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 PKC?.
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Keyword(s):
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Biochemistry |
Publication Date:
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2006 |
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Type:
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Journal article |
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Peer-Reviewed:
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Yes |
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Language(s):
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English |
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Institution:
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Trinity College Dublin |
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Funder(s):
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Health Research Board; Science Foundation Ireland |
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Citation(s):
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McGettrick, A, Brint EK, Palsson-McDermott, EM, Rowe, DC, Golenbock, DT, Gay NJ, Fitzgerald, KA and O?Neill LA `Trif-related adapter molecule is phosphorylated by protein kinase C epsilon during Toll-like receptor 4 signalling? in Proceedings of the National Academy of Sciences, 103, (24), 2006, pp 9196 - 9201 |
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Publisher(s):
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National Academy of Sciences |
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File Format(s):
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application/pdf |
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First Indexed:
2014-05-13 05:57:38 Last Updated:
2015-04-10 05:41:09 |
