| Project/Area Number |
14086205
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kanazawa University |
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Principal Investigator |
YOSHIOKA Katsuji Kanazawa University, Cancer Research Institute, Professor (60200937)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Michihiko Kitasato University, School of Science, Associate Professor (90240994)
棚橋 浩 金沢大学, がん研究所, 助手 (90236654)
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| Project Period (FY) |
2002 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥120,300,000 (Direct Cost: ¥120,300,000)
Fiscal Year 2006: ¥23,400,000 (Direct Cost: ¥23,400,000)
Fiscal Year 2005: ¥23,400,000 (Direct Cost: ¥23,400,000)
Fiscal Year 2004: ¥25,500,000 (Direct Cost: ¥25,500,000)
Fiscal Year 2003: ¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 2002: ¥24,000,000 (Direct Cost: ¥24,000,000)
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| Keywords | cadherin / cerebellum / deveropment and differentiation / genetically engineered mice / JNK / MAP kinase / scaffold protein / signal transduction / 細胞内シグナル伝達 / 精子形成 / 心筋分化 |
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| Research Abstract |
Scaffold proteins of the mammalian MAP kinase (MAPK) cascades are considered having critical roles in spatio-temporal regulation of MAPK pathways by organizing their signaling components into functional modules. We are particularly interested in the functions of these scaffold proteins, mainly c-Jun NH_2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1); a scaffold protein that participates in JNK MAPK cascades, both in vitro and in vivo. Our findings are summarized as follows :
1) We first investigated the JSAP1-null ES cells. We found that the cardiomyogenesis and neurogenesis process in JSAP1-null mutants were seriously impaired, which strongly indicated that JSAP1 plays an important role in cardiomyocyte and neural development (JBC, 2002 ; BBRC, 2005).
2) We also demonstrated that JSAP1 regulates cell movement in cooperation with the focal adhesion kinase (Oncogene, 2002 ; JBC 2005).
3) We further showed that JSAP1 scaffold regulates cell-cell interact
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ions in PC12h cells specifically in the NGF-induced signaling pathway, and does so by modulating N-cadherin (BBRC, 2007) through the knock down experiments in PC12h cells.
4) We also studied JSAP1 and JNK expression in mouse brains. Our results obtained by in situ hybridization and immunohistochemical analyses strongly suggested that JSAP1-JNK signaling plays important roles in developing and adult mouse brains (JNC, 2006).
5) During the development of the cerebellum, massive clonal expansion of granule cell precursors (GCPs) occurs in the outer part of the external granular layer (EGL). We have provided evidence that JSAP1 and active JNK were expressed preferentially in the post-mitotic inner EGL progenitors in the developing cerebellum. Moreover, jsapl deficiency resulted in increasing numbers of proliferating GCPs in mouse embryos. Besides, overexpression of JSAP1 in cultured GCPs led to increased numbers of NeuN-positive cells together with the activation of JNK. Together, these data strongly indicated that JSAP1 promotes the cell-cycle exit and differentiation of GCPs by modulating JNK activity in cerebellar development (in preparation). Less
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