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Trif-related adapter molecule is phosphorylated by PKC{epsilon} during Toll-like receptor 4 signaling.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2006 Jun 13; Vol. 103 (24), pp. 9196-201. Date of Electronic Publication: 2006 Jun 06. - Publication Year :
- 2006
-
Abstract
- PKCepsilon has been shown to play a key role in the effect of the Gram-negative bacterial product LPS; however, the target for PKCepsilon 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 PKCepsilon 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 PKCepsilon-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 PKCepsilon.
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Adaptor Proteins, Vesicular Transport metabolism
Animals
Cell Membrane metabolism
Cells, Cultured
Fibroblasts cytology
Fibroblasts physiology
Humans
Isoenzymes genetics
Lipopolysaccharides metabolism
Mice
Mice, Knockout
Phosphorylation
Protein Kinase C-epsilon genetics
Receptors, Interleukin genetics
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins metabolism
Toll-Like Receptor 4 genetics
Adaptor Proteins, Signal Transducing metabolism
Isoenzymes metabolism
Protein Kinase C-epsilon metabolism
Receptors, Interleukin metabolism
Signal Transduction physiology
Toll-Like Receptor 4 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 103
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 16757566
- Full Text :
- https://doi.org/10.1073/pnas.0600462103