Regulation of TLR4-mediated signaling by IBP/Def6, a novel activator of Rho GTPases. Academic Article uri icon

Overview

abstract

  • TLRs play a fundamental role in innate immune responses. Although Rho GTPases have been implicated in TLR-mediated signaling pathways, the molecules that control their activation in response to TLR engagement are largely unknown. IFN regulatory factor-4-binding protein (IBP; which is encoded by the gene Def6) is a unique type of activator for Rac that plays a crucial role in TCR-mediated signaling and adaptive immune responses. Here, we demonstrate that IBP/Def6 also controls innate immune responses by modulating TLR-induced signaling events. Mice deficient in IBP/Def6 are protected from LPS-induced septic shock. This protection is associated with a decrease in the production of proinflammatory cytokines and is accompanied by diminished activation of MAPKs and NF-kappaB. Our results thus identify IBP/Def6 as a novel component of the TLR4-induced signaling cascade that controls the production of proinflammatory cytokines.

publication date

  • December 12, 2008

Research

keywords

  • DNA-Binding Proteins
  • Immunity, Innate
  • Nuclear Proteins
  • Signal Transduction
  • Toll-Like Receptor 4

Identity

PubMed Central ID

  • PMC2653944

Scopus Document Identifier

  • 61449149464

Digital Object Identifier (DOI)

  • 10.1189/jlb.0308219

PubMed ID

  • 19074553

Additional Document Info

volume

  • 85

issue

  • 3