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 language | English |
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Pages (from-to) | 160-164 |
Number of pages | 5 |
Journal | FEBS Letters |
Volume | 467 |
Issue number | 2-3 |
DOIs | |
Publication status | Published - 2000 Feb 11 |
Externally published | Yes |
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