2000 Fiscal Year Final Research Report Summary
Synthesis and application of functional domain of macrophage scavenger receptor
| Project/Area Number |
10470494
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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 |
医薬分子機能学
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| Research Institution | Osaka University |
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Principal Investigator |
DOI Takefumi Graduate School of Pharmaceutical Sciences Osaka University Professor, 薬学研究科, 教授 (00211409)
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| Co-Investigator(Kenkyū-buntansha) |
IMANISHI Takeshi Graduate School of Pharmaceutical Sciences Osaka University Professor, 薬学研究科, 教授 (40028866)
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| Project Period (FY) |
1998 – 2000
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| Keywords | macrophage / scavenger receptor / model molecule / aggregation / HSP70 / HSP90 / GAPDH / phosphorylation |
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| Research Abstract |
We have synthesized the ligand binding domain of macrophage scavenger receptor (MSR) and investigated the interaction of this molecule to polynucleotides and peptide fragments in apolipoprotein B-100. We found that a certain aggregate form of both polynucleotides and peptides modified by acetic acid or acrolein could compete the ligand binding of MSR.X-ray fiber diffraction analysis suggested that the competitive peptides modified by acrolein form a "cross β structure" as detected on amyloid β-peptide.
We have also synthesized the cytoplasmic domain of MSR.Affinity column with this domain was used for isolating the molecules to associate with MSR.By this column, HSP70, HSP90, aminopeptidase, S-adenosylhomocysteinase, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and a unknown protein were isolated. We are now investigating the function of these proteins for signal transduction of MSR.
We have analized the point mutants of which each serine or threonine residue was substituted by alanine in cytoplasmic domain of MSR.We found that the serine 16, 16th amino acid residue from N-terminus of MSR, was a residue to be phosphorylated by protein kinase and to play an important role for the signal transduction through MSR.
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[Publications] M.Honda, H.Akiyama, Y.Yamada, H.Kondo, Y.Kawabe, M.Takeya, K.Takahashi, H.Suzuki, T.Doi, A.Sakamoto, S.Ookawara, M.Mato, P.J.Gough, D.R.Greaves, S.Gordon, T.Kodama, & M.Matsushita: "Immunohistochemical evidence for a macrophage scavenger receptor in Mato cells and reactive microglia of ischemia and Alzheimer's disease."Biochem.Biophys.Res.Commun.. 245. 734-740 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Y.Takakura, T.Takagi, M.Hashiguchi, M.Nishikawa, F.Yamashita, T.Doi, T.Imanishi, H,Suzuki, T.Kodama, & M.Hashida: "Characterization of plasmid DNA binding and uptake by peritoneal macrophages from class A scavenger receptor knockout mice."Pharmaceutical Research. 16. 503-508 (1999)
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「研究成果報告書概要(欧文)」より
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