| Project/Area Number |
11480174
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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 |
Functional biochemistry
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
IGARASHI Yasuyuki Hokkaido Univ. Grad. School of Pham., Prof., 大学院・薬学研究科, 教授 (70091965)
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| Co-Investigator(Kenkyū-buntansha) |
MOTOHASHI Takeshi Hokkaido Univ. Grad. School of Pham., Inst., 大学院・薬学研究科, 助手 (90301952)
WADA Atsushi Hokkaido Univ. Grad. School of Pham., Inst., 大学院・薬学研究科, 助手 (00301953)
INOKUCHI Jin-ichi Hokkaido Univ. Grad. School of Pham., Asso. Prof., 大学院・薬学研究科, 助教授 (70131810)
木原 章雄 北海道大学, 大学院・薬学研究科, 助手
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2000: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1999: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | sphingolipid / bioactive lipids / sphingosine 1-phosphate / microdomain (raft) / sphingosine kinase / GPCR / receptor / lipid signaling / 糖脂質 / Edg受容体 / 細胞膜ミクロドメイン / シグナル伝達 / G蛋白質 / リゾリン脂質受容体 / 脂質メディエーター / スフィンゴミエリン回路 / スフィンゴシン |
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| Research Abstract |
1) Roles of Sphingosine 1 -phosphate (Sph- 1 -P) in Platelet-related blood vessel biology.
(A) By RT-PCR analysis, we identified that Edg2, 4, 6, and 7 are expressed in human platelets. (B) We purified a novel sphingosine kinase from human platelets. (C) We found for the first time that both Sph-1-P and LPA are released from activated platelets by using new two dimensional TPC separation system. (D) We showed that Sph-1-P released from activated platelets induces in vitro angiogenesis and smooth muscle cell contraction.
2) Besides so-far known sphingosine kinases (1 and 2), we identified and cloned two novel sphingosine kinases (3 and 4).
3) Activation of Rho and FAK through Edg-5 was suggested to regulate cell motility.
4) Studies on Sph-1-P receptors.
(A) We first showed that Edg 1 and Edg 6 are N-glycosylated on Asp residue and suggested the roles of glycosylyation on the receptor dynamics toward microdomain in plasmamembrane. (B) We identified ligand- binding amino acid residues in Edg-6 from computer modeling and mutant analysis.
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