| First Author | McGettrick AF | Year | 2006 |
| Journal | Proc Natl Acad Sci U S A | Volume | 103 |
| Issue | 24 | Pages | 9196-201 |
| PubMed ID | 16757566 | Mgi Jnum | J:111048 |
| Mgi Id | MGI:3652658 | Doi | 10.1073/pnas.0600462103 |
| Citation | McGettrick AF, et al. (2006) Trif-related adapter molecule is phosphorylated by PKC{varepsilon} during Toll-like receptor 4 signaling. Proc Natl Acad Sci U S A 103(24):9196-201 |
| abstractText | 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. |
