TAK1 mediates an activation signal from toll-like receptor(s) to nuclear factor-κB in lipopolysaccharide-stimulated macrophages

Takashi Irie, Tatsushi Muta, Koichiro Takeshige

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Stimulation of monocytes/macrophages with lipopolysaccharide (LPS) results in activation of nuclear factor-κB (NF-κB), which plays crucial roles in regulating expression of many genes involved in the subsequent inflammatory responses. Here, we investigated roles of transforming growth factor-β activated kinase 1 (TGF-TAK1), a mitogen-activated protein kinase kinase kinase (MAPKKK), in the LPS-induced signaling cascade. A kinase-negative mutant of TAK1 inhibited the LPS-induced NF-κB activation both in a macrophage-like cell line, RAW 264.7, and in human embryonic kidney 293 cells expressing toll-like receptor 2 or 4. Furthermore, we demonstrated that endogenous TAK1 is phosphorylated upon simulation of RAW 264.7 cells with LPS. These results indicate that TAK1 functions as a critical mediator in the LPS-induced signaling pathway. Copyright (C) 2000 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)160-164
Number of pages5
JournalFEBS Letters
Volume467
Issue number2-3
DOIs
Publication statusPublished - 2000 Feb 11

Keywords

  • Innate immunity
  • Lipopolysaccharide
  • Macrophage
  • Nuclear factor-κB
  • TAK1
  • Toll-like receptor

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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