Mixed Lineage Kinase LZK Forms a Functional Signaling Complex with JIP-1, a Scaffold Protein of the c-Jun NH2-Terminal Kinase Pathway
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...
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Published in | Journal of biochemistry (Tokyo) Vol. 130; no. 6; pp. 773 - 781 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford University Press
01.12.2001
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Subjects | |
Online Access | Get full text |
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Summary: | 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 NHj terminal kinase (JNK)/stress-activated 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 (MEKKIAN), 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 |
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Bibliography: | 1This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science. A.Ikeda is a recipient of Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists ark:/67375/HXZ-8GGH9R8M-Z ArticleID:130.6.773 istex:D011A662C90901BE9DB48E9507EE6C7849EBC6A5 |
ISSN: | 0021-924X 1756-2651 |
DOI: | 10.1093/oxfordjournals.jbchem.a003048 |