2003 Fiscal Year Final Research Report Summary
Regulation mechanism of a signal transduction by MUK-JNK pathway.
| Project/Area Number |
14580685
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | Yokohama City University |
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Principal Investigator |
HIRAI Syu-ichi Yokohama City University, School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (80228759)
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| Project Period (FY) |
2002 – 2003
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| Keywords | signal transduction / cortex / JNK / migration / neuron |
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| Research Abstract |
c-Jun N-terminal kinase (JNK) is supposed to play fundamental roles in cellular events such as apoptosis and the establishment of planar cell polarity. To date, several MAP kinase kinase kinase (MAPKKK) class protein kinases are identified as upstream activator for JNK. However, when and how they become active in vivo to induce such cellular events via JNK have only partly been elucidated. Protein kinase MUK, also termed DLK or ZPK, is one of such MAPKKK class activator, which is highly expressed in neural tissues of mammals. To explore the significance of the MUK/DLK/ZPK-JNK signaling pathway in vivo, we first examined the expression of MUK/DLK/ZPK-JNK signaling pathway in vivo, we first examined the expression of MUK/DLK/ZPK protein and the distribution of active JNK in developing mouse at different embryonic stages. Immuno-histochemical staining, Western blot, and in-gel kinase assay revealed that the MUK protein level and JNK activity are enhanced potently in immature neurons crossing the intermediate zone of developing mouse neocortex. Adenovirus vector-mediated expression of exogenous MUK in neural precursor cells in utero impaired cell migration across the intermediate zone without affecting their viability and differentiation into immature neurons. Notably, MUK is associated with the particular structures, which are frequently located along microtubules and Golgi apparatus. Finally, loss of polarized organization of microtubules was frequently observed by the forced expression of MUK in culture cells. Taken together, these observations indicate that MUK-JNK pathway regulates neural cell migration in developing neocortex by controlling a cell polarity.
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