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

FEBS Letters

Irie, Takashi¹  Takeshige, Koichiro¹  Muta, Tatsushi¹ 

[1] Department of Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

关键词: Lipopolysaccharide;    TAK1;    Toll-like receptor;    Nuclear factor-κB;    Macrophage;    Innate immunity;    LPS;    lipopolysaccharide;    TNF-α;    tumor necrosis factor-α;    IL;    interleukin;    NF-κB;    nuclear factor-κB;    MAP kinase;    mitogen-activated protein kinase;    TLR;    toll-like receptor;    TGF;    transforming growth factor;    TAK1;    TGF-β activated kinase 1;    IRAK;    IL-1 receptor-associated kinase;    TRAF;    TNF receptor-associated factor;    NIK;    NF-κB-inducing kinase;    HEK;    human embryonic kidney;    SDS–PAGE;    sodium dodecylsulfate–polyacrylamide gel electrophoresis;   

DOI  :  10.1016/S0014-5793(00)01146-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown