Protein phosphatase 4 negatively regulates LPS cascade by inhibiting ubiquitination of TRAF6.
TRAF6 is an E3 ubiquitin ligase that transduces signals from members of the TLR/IL-1R family. Multiple molecules have been found to associate with TRAF6 and exert their functions in this pathway. Herein, by yeast two-hybrid screen using TRAF6 as bait, we identified PP4 as a potential TRAF6-interacting protein. PP4 physically ... interacted with TRAF6 and was recruited to TLR4 complex upon LPS stimulation. PP4 negatively regulated LPS-induced and TRAF6-mediated NF-kappaB activation by inhibiting the ubiquitination of TRAF6. LPS stimulation also induced the expression of PP4. Taken together, our findings suggest that PP4 is a negative feedback regulator of LPS/TLR4 pathway.
Mesh Terms:
Animals, Cell Line, Feedback, Physiological, Humans, Lipopolysaccharides, Mice, NF-kappa B, Phosphoprotein Phosphatases, TNF Receptor-Associated Factor 6, Toll-Like Receptor 4, Two-Hybrid System Techniques, Ubiquitin-Protein Ligases, Ubiquitination
Animals, Cell Line, Feedback, Physiological, Humans, Lipopolysaccharides, Mice, NF-kappa B, Phosphoprotein Phosphatases, TNF Receptor-Associated Factor 6, Toll-Like Receptor 4, Two-Hybrid System Techniques, Ubiquitin-Protein Ligases, Ubiquitination
FEBS Lett.
Date: Aug. 20, 2008
PubMed ID: 18634786
View in: Pubmed Google Scholar
Download Curated Data For This Publication
80477
Switch View:
- Interactions 5
- PTM Genes 1