JNK-interacting protein 3 associates with Toll-like receptor 4 and is involved in LPS-mediated JNK activation

Tetsuya Matsuguchi, Akio Masuda, Kenji Sugimoto, Yoshiyuki Nagai, Yasunobu Yoshikai

    研究成果: Contribution to journalArticle査読

    76 被引用数 (Scopus)

    抄録

    Lipopolysaccharide (LPS) is recognized by Toll-like receptor (TLR) 4 and activates NF-κB and a set of MAP kinases. Here we have investigated proteins associated with the cytoplasmic domain of mouse TLR4 by yeast two-hybrid screening and identified JNK-interacting protein 3 (JIP3), a scaffold protein for JNK, as a TLR4-associated protein. In mammalian cells, JIP3, through its N-terminal region, constitutively associates with TLR4. The association is specific to JIP3, as the two other JIPs, JIP1 and JIP2, failed to bind TLR4. In HEK 293 cells exogenously expressing TLR4, MD2 and CD14, co-expression of JIP3 significantly increased the complex formation of TLR4-JNK and LPS-mediated JNK activation. In contrast, expression of C-terminally truncated forms of JIP3 impaired LPS-induced JNK activation in a mouse macrophage cell line, RAW264.7. Moreover, RNA interference of JIP3 inhibited LPS-mediated JNK activation. In RAW264.7 cells, JIP3 associates MEKK-1, but not with TAK-1. Finally, JIP3 also associates with TLR2 and TLR9, but not with TLR1 or TLR6. Altogether, our data indicate the involvement of JIP3 in JNK activation in downstream signals of some TLRs.

    本文言語英語
    ページ(範囲)4455-4464
    ページ数10
    ジャーナルEMBO Journal
    22
    17
    DOI
    出版ステータス出版済み - 9 1 2003

    All Science Journal Classification (ASJC) codes

    • Neuroscience(all)
    • Molecular Biology
    • Biochemistry, Genetics and Molecular Biology(all)
    • Immunology and Microbiology(all)

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