Mixed lineage kinase ZAK utilizing MKK7 and not MKK4 to activate the c-Jun N-terminal kinase and playing a role in the cell arrest |
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Authors: | Yang Jaw-Ji |
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Institution: | School of Dentistry, Chung-Shan Medical University, 402, Taichung, Taiwan. jjyang@smu.edu.tw |
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Abstract: | The leucine-zipper (LZ) and sterile-alpha motif (SAM) kinase (ZAK) belongs to the MAP kinase kinase kinase (MAP3K) when upon over-expression in mammalian cells activates the JNK/SAPK pathway. The mechanisms by which ZAK activity is regulated are not well understood. Co-expression of dominant-negative MKK7 but not MKK4 and ZAK significantly attenuates JNK/SAPK activation. This result suggests that ZAK activates JNK/SAPK mediated by downstream target, MKK7. Expression of ZAK but not kinase-dead ZAK in 10T1/2 cells results in the disruption of actin stress fibers and morphological changes. Therefore, ZAK activity may be involved in actin organization regulation. Expression of wild-type ZAK increases the cell population in the G(2)/M phase of the cell cycle, which may indicate G(2) arrest. Western blot analysis shows that the decreased cyclin E level correlated strongly with the low proliferative capacity of ZAK-expressed cells. |
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Keywords: | Leucine-zipper (LZ) and sterile-α motif (SAM) kinase (ZAK) Mixed lineage kinase (MLK) JNK/SAPK Cell cycle |
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