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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Molecular basis for lipopolysaccharide mimetic action of Taxol and flavolipin.

We previously reported that Taxol, which mimics the action of LPS on murine macrophages, induces signals via mouse TLR4/MD-2, but not via human TLR4/MD-2. Here we investigated the molecular basis for this species-specific action of Taxol. Expression of mouse MD-2 conferred both LPS and Taxol responsiveness on HEK293 cells expressing mouse TLR4, whereas expression of human MD-2 conferred LPS responsiveness alone, suggesting that MD-2 is responsible for the species-specificity of Taxol responsiveness. Furthermore, mouse MD-2 mutants, in which Gln-22 was changed to other amino acids, showed dramatically reduced ability to confer Taxol responsiveness, although their ability to confer LPS responsiveness was not affected. These results indicated that Gln-22 of mouse MD-2 is essential for Taxol signaling, but not for LPS signaling. In this study, we also found that the TLR4/MD-2 complex, together with CD14, mediated signal transduction induced by flavolipin, an amino acid-containing lipid unique to Flavobacterium meningosepticum.[1]


  1. Molecular basis for lipopolysaccharide mimetic action of Taxol and flavolipin. Kawasaki, K., Gomi, K., Kawai, Y., Shiozaki, M., Nishijima, M. J. Endotoxin Res. (2003) [Pubmed]
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