Molecular mechanism of cellular response induced by dynamic metabolism of membrane phospholipid
| Project/Area Number |
17390065
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Kobe University |
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Principal Investigator |
SAITO Naoaki Biosignal Research Center, Professor, バイオシグナル研究センター, 教授 (60178499)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAI Yasuhito Biosignal Research Center, Associate Professor, バイオシグナル研究センター, 助教授 (60263399)
UEYAMA Takehiko Biosignal Research Center, Assistant Professor, バイオシグナル研究センター, 助手 (80346254)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2006: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2005: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | protein kinase C / live imaging / lipid / diacylglycerol kinase / phagocytosis / NADPH oxidase / Spinocerebellar ataxia / ischemia / ジアシルグリセロール / 細胞周期 / 核移行 / 凝集体形成 / 遺伝子操作動物 / GFP / 脂質メッセンジャー / カスケード / 神経可塑性 / ファゴサイトーシス |
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| Research Abstract |
Recent technical development has enabled us to monitor the production, movement and signaling of lipid messengers in living cells using probes for specific lipids. In this project, we performed the spatio-temporal analysis using various probes for lipid messengers to elucidate when and where the lipid signaling occurs within the cells in physiological cellular responses. As a result, we obtained the results below.
1) Live imaging of signaling molecules (Protein kinase C (PKC) subtypes, Rac subtypes, p47^<Phox>, p40^<Phox>) in phagocytosis. Each molecule having different lipid binding ability translocated to the specific intracellular compartment in different time course. The finely tuned control of targeting mechanism of signaling molecules to lipid regulate the superoxide production in phagocytosis.
2) Functional and molecular interaction of Diacylglycerol (DG)-PKC-DG kinase (DGK) pathway. Direct binding between PKC and DGK and the regulation of each enzymatic activity by the binding were demonstrated using live-imaging techniques. PKC binds to DGK on the plasma membrane and phosphorylates DGK at S776and S779. The phosphorylated DGK is then activated and terminates PKC pathway by convert DG to PA on the plasma membrane.
3) Nuclear translocation of DGKgamma requires its Cl domain but not the kinase activity. Nuclear DGKgamma controls cell cycle.
4) Aggregation of mutant PKCgamma within cells may cause Spinocerebellar ataxia type 14 (SCA14).
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Report
(3 results)
Research Products
(72 results)
