GSBS Student Publications

Title

Trif-related adapter molecule is phosphorylated by PKC{epsilon} during Toll-like receptor 4 signaling

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Date

6-8-2006

Document Type

Article

Medical Subject Headings

Adaptor Proteins, Signal Transducing; Adaptor Proteins, Vesicular Transport; Animals; Cell Membrane; Cells, Cultured; Fibroblasts; Humans; Isoenzymes; Lipopolysaccharides; Mice; Mice, Knockout; Phosphorylation; Protein Kinase C-epsilon; Receptors, Interleukin; Recombinant Fusion Proteins; Signal Transduction; Toll-Like Receptor 4

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.

Rights and Permissions

Citation: 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

Related Resources

Link to article in PubMed

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

16757566