期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 24, 页码 9196-9201出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0600462103
关键词
innate immunity; LPS; myristoylation
资金
- MRC [G0400007] Funding Source: UKRI
- Medical Research Council [G0400007] Funding Source: researchfish
- Medical Research Council [G1000133, G0400007] Funding Source: Medline
PKC epsilon has been shown to play a key role in the effect of the Gram-negative bacterial product LPS; however, the target for PKC epsilon 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-beta (Trif), and Trif-related adapter molecule (TRAM). Here we show that TRAM is transiently phosphorylated by PKC epsilon 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 epsilon-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 epsilon.
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