1997 Fiscal Year Final Research Report Summary
Growth factor midkine : Biological significance, action mechanism, tissue repairing activity and relationship with diseases.
| Project/Area Number |
08457035
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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 |
General medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
MURAMATSU Takashi Nagoya University School of Medicine, Professor, 医学部, 教授 (00030891)
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| Co-Investigator(Kenkyū-buntansha) |
KUROSAWA Nobuyuki Nagoya University School of Medicine, Research Associate, 医学部, 助手 (50241253)
MURAMATSU Hisako Nagoya University School of Medicine, Research Associate, 医学部, 助手 (50182134)
KADOMATSU Kenji Nagoya University of Medicine, Associate Professor, 医学部, 助教授 (80204519)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Midkine / Hepari / NMR / Synaps / Cancer / Neutrophil / Rheumatoid arthritic / Calcium mobilization |
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| Research Abstract |
1.3D structure of midkine was determined NMR.Midkine consists of 2 domains, which have 3 anitipararel beta-sheets. Site-directed mutagenesis of C-domain, which has biological activity, enabled us to identify amino acids required for neurite outgrowth and plasminogen activator enhancing activity. 2.Midkine had neutrophil chemotactic activity, and was found in synovial fluid of rheumatoid arthritis patients, indicating its close correlation with inflammation. Midkine promotes Ca^<2+> mobilization in neutrophils ; by the use of specific inhibitors of signal transduction, tyrosine kinase, P13 kinase and a G-protein-linked receptor were proposed to be involved in the process. 3.Knockout mice lacking midkine gene were produced. They developed normally, but postnatal development of the hippocampus was delayd. 4.Injection of midkine mRNA into Xenopus embryos showed that midkine suppressed mesoderm induction and promoted development of head neurons. Signal transduction downstream from Smad 2 appeared to interact with midkine signaling pathway. 5.Midkine coated beads induced clustering of acetylcholine receptor in muscle cells. Together with midkine expression in synapses, midkine was concluded to be a factor which was secreted from neurons and promoted synaptogenesis. 6.Truncated midkine mRNA devoid of N terminal domain was expressed in a manner specific for tumor. The lymph node metastases showed strong expression of the truncated form. Serum levels of midkine was frequently elevated in cancer patients, especially in those with lung carcinomas.
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Research Products
(12 results)
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[Publications] Adachi, Y., Matsubara, S., Pedraza, C., Ozawa, M., Tsutsui, J., Takamatsu, H., Noguchi, H., Akiyama, T.and Muramatsu, T.: "Midkine as a novel target gene for the Wilms'tumor suppressor gene (WT1)." Oncogene. 13. 2197-2203 (1996)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kojima, S., Inui, T., Muramatsu, H., Suzuki, Y., Kadomatsu, K., Yoshizawa, M., Hirose, S., Kimura, T., Sakakibara, S.and Muramatsu, T.: "Dimerization of midkine by transglutaminase and its functional implication." J.Biol.Chem.272. 9410-9416 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Takada, T., Toriyama, K., Muramatsu, H., Song, X.-J., Torii, S.and Muramatus, T.: "Midkine, a retinoic acid-inducible heparin-binding cytokine in inflammatory responses : chemotactic activity to neutrophils and association with inflammatory synovitis." J.Biochem.122. 453-458 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Asai, T., Watanabe, K., Ichihara-Tanaka, K., Kaneda, N., Kojima, S., Iguchi, A., Inagaki, F.and Muramatsu, T.: "Identification of heparin-binding sites in midkine and their role in neurite-promotion." Biochem.Biophys.Res.Common.236. 66-70 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Iwasaki, W., Nagata, K., Hatanaka, H., Imui, T., Kimura, T., Muramatsu, T., Yoshida, K., Tasumi, M.and Inagaki, F.: "Solution structure of midkine, a new heparin binding growth factor." EMBOJ.16. 6936-6946 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Takada, T., Kinkori, T., Muramatsu, H., Hayakawa, A., Torri, S.and Muramatsu, T.: "Midkine, a retinoic acid-inducible heparin-binding cytokine, is a novel regulator of intra cellular calcium ion in human neutrophils." Biochem.Biophys.Res.Commun.241. 756-761 (1997)
Description
「研究成果報告書概要(欧文)」より
