Mixed Lineage Kinase LZK Forms a Functional Signaling Complex with JIP-1, a Scaffold Protein of the c-Jun NH2-Terminal Kinase Pathway.
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概要
- 論文の詳細を見る
Leucine zipper-bearing kinase (LZK) is a novel member of the mixed lineage kinase (MLK) protein family, the cDNA of which was first cloned from a human brain cDNA library [Sakuma, H., Ikeda, A., Oka, S., Kozutsumi, Y., Zanetta, J. -P., and Kawasaki, T. (1997) J. Biol. Chem. 272, 28622-28629]. Several MLK family proteins have been proposed to function as MAP kinase kinase kinases in the c-Jun NH2 terminal kinase (JNK)/stressactivated protein kinase (SAPK) pathway. In the present study, we demonstrated that, like other MLKs, LZK activated the JNK/SAPK pathway but not the ERK pathway. LZK directly phosphorylated and activated MKK7, one of the two MAPKKs in the JNK/SAPK pathway, to a comparable extent to a constitutive active form of MEKK1 (MEKK1ΔN), suggesting a biological role of LZK as a MAPKKK in the JNK/SAPK pathway. Recent studies have revealed the essential roles of scaffold proteins in intracellular signaling pathways including MAP kinase pathways. JIP-1, one of the scaffold proteins, has been shown to be associated with MLKs, MKK7, and JNK [Whitmarsh, A. J., Cavanagh, J., Tournier, C., Yasuda, J., and Davis, R. J. (1998) Science 281, 1671-1674], suggesting the presence of a selective signaling pathway including LZK, MKK7, and JNK. Consistent with this hypothesis, we provided evidence that LZK is associated with the C-terminal region of JIP-1 through its kinase catalytic domain. In addition, LZK-induced JNK activation was markedly enhanced when LZK and JNK were co-expressed with JIP-1. These results constituted important clues for understanding the molecular mechanisms regulating the signaling specificities of various JNK activators under different cellular conditions.
- 社団法人 日本生化学会の論文
著者
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Ikeda Atsushi
Department Of Cardiology Kurashiki Central Hospital
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OKA Shogo
Department of Biological Chemistry and CREST (Core Research for Educational Science and Technology)
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KOZUTSUMI Yasunori
Department of Biological Chemistry and CREST (Core Research for Educational Science and Technology)
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Nishida Eisuke
Department Of Biophysics And Biochemistry Faculty Of Science University Of Tokyo
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Kawasaki Toshisuke
Department Of Biochemistry Kyoto University
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Moriguchi Tetsuo
Department Of Cell And Developmental Biology Laboratoty Of Signal Transduction Graduate School Of Biostudies Kyoto University
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Masaki Megumi
Department of Biological Chemistry and CREST (Core Research for Educational Science and Technology Project.
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Hasegawa Keiji
Department of Biological Chemistry and CREST (Core Research for Educational Science and Technology Project.
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Moriguchi Tetsuo
Department of Cell and Developmental Laboratory of Signal Transduction. Graduate School of Biostudies. Kyoto University
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