Role of TLR4 tyrosine phosphorylation in signal transduction and endotoxin tolerance

AE Medvedev, W Piao, J Shoenfelt, SH Rhee… - Journal of Biological …, 2007 - ASBMB
In this study, we examined whether tyrosine phosphorylation of the Toll-IL-1 resistance (TIR)
domain of Toll-like receptor (TLR) 4 is required for signaling and blocked in endotoxin
tolerance. Introduction of the P712H mutation, responsible for lipopolysaccharide (LPS)
unresponsiveness of C3H/HeJ mice, into the TIR domain of constitutively active mouse
ΔTLR4 and mutation of the homologous P714 in human CD4-TLR4 rendered them signaling-
incompetent and blocked TLR4 tyrosine phosphorylation. Mutations of tyrosine residues …