GSBS Student Publications
Title
Trif-related adapter molecule is phosphorylated by PKC{epsilon} during Toll-like receptor 4 signaling
Publication Date
2006-06-08
UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Document Type
Article
Disciplines
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
10.1073/pnas.0600462103
Source
Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9196-201. Epub 2006 Jun 6. Link to article on publisher's site
Journal/Book/Conference Title
Proceedings of the National Academy of Sciences of the United States of America
Related Resources
PubMed ID
16757566
Repository Citation
McGettrick, Anne F.; Brint, Elizabeth K.; Palsson-McDermott, Eva M.; Rowe, Daniel C.; Golenbock, Douglas T.; Gay, Nicholas J.; Fitzgerald, Katherine A.; and O'Neill, Luke A. J., "Trif-related adapter molecule is phosphorylated by PKC{epsilon} during Toll-like receptor 4 signaling" (2006). GSBS Student Publications. 828.
https://escholarship.umassmed.edu/gsbs_sp/828