Cutting edge: Gln(22) of mouse MD-2 is essential for species-specific lipopolysaccharide mimetic action of taxol

MD-2 associates with the extracellular domain of Toll-like receptor 4 (TLR4 ) and greatly enhances LPS signaling via TLR4, Taxol, which mimics the acti on of LPS on murine macrophages, induces signals via mouse TLR4-MD-2, but n ot via human TLR4-MD-2. Here we investigated the molecular basis for this s pecies-specific action of Taxol. Expression of mouse MD-2 conferred both LP S and Taxol responsiveness on human embryonic kidney 293 cells expressing m ouse TLR4, whereas expression of human MD-2 conferred LPS responsiveness al one, suggesting that MD-2 is responsible for the species-specificity as to Taxol responsiveness. Furthermore, mouse MD-2 mutants, in which Gln(22) was changed to other amino acids, showed dramatically reduced ability to confe r Taxol responsiveness, although their ability to confer LPS responsiveness was not affected. These results indicated that Gln(22) of mouse MD-2 is es sential for Taxol signaling but not for LPS signaling.