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.
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.
Yang
Jaw-Ji
JJ
School of Dentistry, Chung-Shan Medical University, 402, Taichung, Taiwan. jjyang@smu.edu.tw
D000199:Actins / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D048429:Cell Size / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; D020930:MAP Kinase Kinase Kinases; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured
D000199:Actins; D018797:Cell Cycle Proteins; D011494:Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C413047:MAP3K20 protein, human; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; C482559:MAP2K4 protein, human; C482569:MAP2K7 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases