Cutting Edge: Gln~22 of Mouse MD-2 Is Essential for Sepcies-Specific Lipopolysaccharide Mimetic Action of Taxol

摘要

1 MD-2 associates with the extracellular domain of Toll-like receptor 4 (TLR4) and greatly enhances LPS signaling via TLR4. I Taxol, which mimics the action of LPS on murine macro- 1 phages, 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 human embryonic kidney 293 cells expressing mouse TLR4, whereas expression of human MD-2 conferred LPS responsiveness alone, suggesting that MD-2 is responsible for the species-spec- ificity as to Taxol responsiveness. Furthermore, mouse MD-2 mutants, in which Gln22 was changed to other amino acids, showed dramatically reduced ability to confer Taxol respon- siveness, although their ability to confer LPS responsiveness was not affected. These results indicated that Gln22 of mouse MD-2 is essential for Taxol signaling but not for LPS signaling.