| Project/Area Number |
10672085
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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 |
医薬分子機能学
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| Research Institution | Institute for Molecular and Cellular Regulation |
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Principal Investigator |
TOMURA Hideaki Institute for Molecular and Cellular Regulation : Department of Cell Biology : Research Associate, 生体調節研究所・調節機構部門, 助手 (70217553)
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| Co-Investigator(Kenkyū-buntansha) |
SHO Kimie Institute for Molecular and Cellular Regulation : Department of Cell Biology : Research Assistant, 生体調節研究所・調節機構部門, 教務員 (40201561)
OKAJIMA Fumikazu Institute for Molecular and Cellular Regulation : Department of Molecular Physiology : Professor, 生体調節研究所・調節因子部門, 教授 (30142748)
TAKEDA Jun Institute for Molecular and Cellular Regulation : Department of Cell Biology : Professor, 生体調節研究所・調節機構部門, 教授 (40270855)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | sphingosine 1-phosphate / cell-surface receptor / Edg-1 / Edg-3 / Edg-5 / Edg-6 / Signal transduction / CHO cell / スフィンゴシン1-リン酸受容体 / 受容体 / ホスホリパーゼC / カルシウム / HL60細胞 |
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| Research Abstract |
By this research project for two years, we found some new things as follows.
1. Molecular cloning of sphingosine 1-phospahte (S1P) receptor- It has been reported that the endothelial differentiation gene-1 (Edg-1), Edg-3, Edg-5 were the S1P receptors. On the other hand, we obtained some evidences that some cellular responses elicited by S1P might not be mediated by these receptors. So we tried to identify another S1P receptor and found that Edg-6, which was recently identified as an orphan G-protein-coupled receptor, was the another S1P receptor.
2. Signaling Mechanisms of the S1P receptors- To evaluate and compare the intrinsic activity of the each S1P receptor subtypes in the regulation of multiple signaling pathways, we prepared the Chinese hamster ovary (CHO) cell lines that permanently express the respective S1P receptor subtype to a comparative level. Using these cell lines, we found these things as follows. (1) There was no significant difference in the expressing numbers of the S1P receptors and their affinities to S1P. (2) S1P selectively regulated multiple signaling pathways according to the receptor subtype. For example, the rank order of their intrinsic activity of S1P receptor subtype was Edg-3>Edg-5>Edg-1>Edg-6 to induce activation of PLC/Ca ィイD12+ィエD1 system. On the other hand, as for cell migration activity, Edg-3 and Edg-1 were equally potent, but Edg-5 and Edg-6 were ineffective.
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