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

Abstract:

:Stimulation of monocytes/macrophages with lipopolysaccharide (LPS) results in activation of nuclear factor-kappaB (NF-kappaB), which plays crucial roles in regulating expression of many genes involved in the subsequent inflammatory responses. Here, we investigated roles of transforming growth factor-beta 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-kappaB 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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Irie T,Muta T,Takeshige K

doi

10.1016/s0014-5793(00)01146-7

keywords:

subject

Has Abstract

pub_date

2000-02-11 00:00:00

pages

160-4

issue

2-3

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(00)01146-7

journal_volume

467

pub_type

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