1995 Fiscal Year Final Research Report Summary
Receptor structure and inhibition of midkine, a growth factor controled by retinoic acid
| Project/Area Number |
06454645
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Structural biochemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
MURAMATSU Takashi Nagoya University, School of Medicine, Department of Biochemistry, Professor, 医学部, 教授 (00030891)
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| Co-Investigator(Kenkyū-buntansha) |
MURAMATSU Hisako Nagoya University, School of Medicine, Department of Biochemistry, Assistanat Pr, 医学部, 助手 (50182134)
KADOMATSU Kenji Nagoya University, School of Medicine, Department of Biochemistry, Assistant Pro, 医学部, 講師 (80204519)
KANEDA Norio Nagoya University, School of Medicine, Department of Biochemistry, Associate Pro, 医学部, 助教授 (00144139)
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| Project Period (FY) |
1994 – 1995
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| Keywords | midkine / heparin / growth factor / tissue repair / receptor / heparan sulfate / neurite outgrowth / cancer |
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| Research Abstract |
We studied on structure and function of midkine (MK). Chemically synthesized C-terminal half molecule of MK has neurite outgrowth promoting activity and heparin binding activity. A mutant MK whose putative heparin binding sites were altered by in vitro mutagenesis lost neurite promoting activity, indicating that heparing binding activity correlates with neurite promoting activity. Structural requirements for binding to MK was analyzed by chemically modified heparing and heparin-derived oligosaccharides. All of sulfate groups (2-0,6-0,2-N) were required for inhibition of neurite promoting activity. The size of heparin oligosaccharide necessary for the inhibition was about 20-mer. On the other hand, a putative MK receptor was disclosed by analysis of membrane proteins binding to MK column. A histochemical method to localize the MK receptor of protein nature was also established. We also obtained results indicating the correlation of MK expression and cancer, brain and heart infarction and rheumatoid arthritis. A sensitive method to determine MK levels was also devised, enabling MK assay in serum samples.
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[Publications] Muramatsu, H., Inui, T., Kimura, T., Sakakibara, S., Song, X., Murata, H.and Muramatsu, T: "Localization of heparin-binding, neurite outgrowth and antigenic regions in midkine molecule" Biochem.Biophys.Res.Commun. 203. 1131-1139 (1994)
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「研究成果報告書概要(欧文)」より
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[Publications] Kojima, S., Inui, T., Kimura, T., Sakakibara, S., Muramatsu, H., Amanuma, H., Maruta, H.and Muramatsu, T.: "Synthetic peptides derived from midkine enhances plasminogen activator in bovine aortic endothelial cells" Biochem.Biophys.Res.Commun.206. 468-473 (1994)
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「研究成果報告書概要(欧文)」より
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[Publications] Mitsiadis, T.A., Salmivirta, M., Muramatsu, T., Muramatsu, H., Rauvala, H., Lehtonen, E.and Thesleff, I.: "Expression of the heparin-binding cytokines, midkine (MK) and HB-GAM (pleiotrophin) is associated with epithelial-mesenchymal interactions during fetal development and organogenesis" Development. 121. 37-51 (1995)
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[Publications] Kaneda, N., Talukder, A.H., Ishihara, M., Hara, S., Yoshida, K.and Muramatsu, T: "Structural characteristics of heparin-like domain required for interaction of midkine with embryonic neurons" Biochem, Biophys.Res.Commun.(in press). (1996)
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「研究成果報告書概要(欧文)」より
