Cutting edge: Gln22 of mouse MD-2 is essential for species-specific lipopolysaccharide mimetic action of Taxol1

K. Kawasaki, K. Gomi, M. Nishijima

    Research output: Contribution to journalArticlepeer-review

    60 Citations (Scopus)

    Abstract

    MD-2 associates with the extracellular domain of Toll-like receptor 4 (TLR4) and greatly enhances LPS signaling via TLR4. 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 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-specificity 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 responsiveness, 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.

    Original languageEnglish
    Pages (from-to)11-14
    Number of pages4
    JournalJournal of Immunology
    Volume166
    Issue number1
    DOIs
    Publication statusPublished - 2001 Jan 1

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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