Premium
JNK‐interacting protein 3 associates with Toll‐like receptor 4 and is involved in LPS‐mediated JNK activation
Author(s) -
Matsuguchi Tetsuya,
Masuda Akio,
Sugimoto Kenji,
Nagai Yoshiyuki,
Yoshikai Yasunobu
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg438
Subject(s) - tlr4 , kinase , microbiology and biotechnology , hek 293 cells , tlr2 , toll like receptor , chemistry , tlr9 , receptor , biology , signal transduction , biochemistry , innate immune system , gene expression , gene , dna methylation
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.