Mixed lineage kinase LZK and antioxidant protein-1 activate NF-κB synergistically

Megumi Masaki, Atsushi Ikeda, Eriko Shiraki, Shogo Oka, Toshisuke Kawasaki

研究成果: ジャーナルへの寄稿学術論文査読

39 被引用数 (Scopus)

抄録

Leucine zipper-bearing kinase (LZK) is a novel member of the mixed lineage kinase (MLK) family [Sakuma, H., Ikeda, A., Oka, S., Kozutsumi, Y., Zanetta, J. P., and Kawasaki, T. (1997) J. Biol. Chem. 272, 28622-28629]. We have previously shown that LZK activates the c-Jun-NH2 terminal kinase (JNK) pathway, but not the extracellular signal-related kinase (ERK) pathway, by acting as a mitogen-activated protein kinase kinase kinase (MAPKKK) [Ikeda, A., Hasegawa, K., Masaki, M., Moriguchi, T., Nishida, E., Kozutsumi, Y., Oka, S., and Kawasaki, T. (2001) J. Biochem. 130, 773-781]. However, the mode of activation of LZK remains largely unknown. By means of a yeast two-hybrid screening system, we have identified a molecule localized to mitochondria, antioxidant protein-1 (AOP-1), that binds to LZK and which acts as a modulator of LZK activity. Recently, several MAPKKKs involved in the JNK pathway, such as MEKK1, TAK1 and MLK3, were shown, using over-expression assay systems, to activate a transcription factor, NF-κB, through activation of the IKK complex. Using similar assay systems, we demonstrated that LZK activated NF-κB-dependent transcription through IKK activation only weakly, but this was reproducible, and that AOP-1 enhanced the LZK-induced NF-κB activation. We also provided evidence that LZK was associated directly with the IKK complex through the kinase domain, and that AOP-1 was recruited to the IKK complex through the binding to LZK.

本文言語英語
ページ(範囲)76-83
ページ数8
ジャーナルEuropean Journal of Biochemistry
270
1
DOI
出版ステータス出版済み - 2003
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学

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