| Project/Area Number |
12480209
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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 |
Molecular biology
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| Research Institution | Natiomal Institute for Basic Biology (2001)
The University of Tokyo (2000) |
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Principal Investigator |
KATSUKI Motoya Natiomal Institute for Basic Biology, Director in General, 基礎生物学研究所, 所長 (20051732)
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| Co-Investigator(Kenkyū-buntansha) |
饗場 篤 東京大学, 医科学研究所, 助教授 (20271116)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2001: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2000: ¥9,100,000 (Direct Cost: ¥9,100,000)
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| Keywords | small G protein / H-Ras / N-Ras / K-Ras / Signal Transduction / Long Term Potentiation / Hippocampus / knockout mice / Ras / NM-DA受容体 / ハックアウトマウス / トランスジェニックマウス / チロシンリン酸化 / H-ras / K-ras |
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| Research Abstract |
Glutamate receptors that are major excitatory neurotransmitter receptors in the central nervous system (CNS) lead to neuronal cell death when they are overactivated. Therefore, there may be some mechanisms that make a balance between excitotoxic and surviving signals when the receptors are normally activated. We have found that the H-Ras proteins are involved in the NMDA receptor tyrosine phosphorylation and suppress the Long-Term potentiation of the CAl region of the mouse hippocampus. We also found that NMDA stimulation, which conveys Ca^<2+> in-flux into the cell through the NMDA receptor channel, dramatically decreases tyrosine phosphorylation of NR2B subunit of the receptor in hippocampal slices as well as hippocampal cultured cells. This NMDA signaling is mediated by NR2B subunit because blockade of NR2B by a specific antagonist eliminates activation of the ERK and p38 MAPK activation and tyrosine dephosphorylation of NR2B and gene disruption of NR2B eliminates ERK activation by NMDA stimulation. Therefore, NR2B subunit of NMDA receptor regulates ERK pathway, p38 MAPK pathway and own phosphorylation upon NMDA stimulation to modulate a balance between excitotoxic and surviving signals.
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