| Project/Area Number |
10672190
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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 |
Laboratory medicine
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| Research Institution | Osaka Medical College |
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Principal Investigator |
HATANAKA Michiyo Kobe Tokiwa College Associate Professor, 衛生技術科, 助教授 (50218484)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | GPI-anchored protein / signal transduction / CD59 / dimer formation / T cell activation / caveolin / ATL / 細胞内カルシウム濃度 / 補体C9 / ペプチド / 補体制御因子 / GPI-アンカー蛋白 / 細胞内Ca^<2+> / C9 / 架橋試薬 |
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| Research Abstract |
Various cell surface proteins are anchored to cell membranes via a glycosyl-phosphatidylinositol (GPI) anchor. Although these proteins function as signaling molecules, mechanisms involved in the signaling are largely unknown. In this study we focused on a GPI-anchored complement regulatory protein, CD59, as a model for elucidating the mechanisms involved in the GPI-anchored protein mediating signaling.
We identified a CD59-associating protein by cross-linking surface proteins by chemical cross-linker and revealed that the protein is CD59 molecule itself. We also developed the method for direct measurement of CD59 signaling by means of a C9 peptide as a ligand. By ligation with the C9 peptide, specific increase in intracellular Ca2+ was detected. These findings enable the direct assessment of CD59 signaling rather than by activation with Ab cross-linking.
GPI-anchored proteins are distributed on membrane domains designated "rafts". Caveolin, a main protein on one type of rafts (caveolae), functions as a key molecule in various types of signaling. To know whether caveolin is involved in CD59 signaling, we tested caveolin expression in blood and blood cell lines in which CD59 signaling is identified. To our surprise none of them expressed caveolin. Only sub line of adult T cell leukemia (ATL) cell lines in a ctivated states expressed caveolin. We are now on the way to elucidate the function of caveolin in CD59 signaling using these positive cells.
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