2001 Fiscal Year Final Research Report Summary
Identification and characterization of tissue specific active sites in the laminins
| Project/Area Number |
11470480
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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 |
Biological pharmacy
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
NOMIZU Motoyoshi Hokkaido University, Graduate of School of Environmental Earth Science, Associate Professor, 大学院・地球環境科学研究科, 助教授 (00311522)
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| Co-Investigator(Kenkyū-buntansha) |
KURATOMI Yuichiro Kyushu University, School of Medicine, Lecture, 医学部, 講師 (30225247)
UTANI Atsushi Chiba University, School of Medicine, Lecture, 付属病院・皮膚科, 講師 (10292707)
NISHI Norio Hokkaido University, Graduate of School of Environmental Earth Science, Professor, 大学院・地球環境科学研究科, 教授 (70001857)
KADOYA Yuichi Kitasato University, School of Medicine, Lecture, 医学部, 講師 (10185887)
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| Project Period (FY) |
1999 – 2001
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| Keywords | basement membrane / laminin / integrin / cell attachment / peptide / integrin |
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| Research Abstract |
Laminins are heterotrimeric basement membrane glycoproteins consisting of genetically distinct α, β, and γ chains. So far, five α, three β, and three γ chains have been identified, and at least fifteen isoforms (Laminin-1-15) are formed by various combinations of each subunit. Laminins have diverse biological activities including promotion of cell adhesion, growth, migration, neurite outgrowth, and differentiation. Our goal is to understand the biological role of the laminins in normal development and disease processes and to apply the active sequences for therapeutic application including tissue regeneration and engineering. Our approach has been to localize cell adhesion sites on the laminin molecules using a large set of synthetic peptides and recombinant proteins. We have identified about 20 active sequences from the laminin-1 using a systematic screening for cell binding sites with 673 overlapping synthetic peptides. First, we have focused on the biological functions of the lamini
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n αchain G domains and screened active sites using a recombinant protein and synthetic peptides. We prepared various recombinant proteins, comprising the G domains of laminin α1, α3 and α4 chains, and tested their cell attachment activity. Several recombinant proteins showed cell attachment and neurite outgrowth activities. We also synthesized more than 300 overlapping peptides covering the entire G domains and tested their cell attachment activity sing peptide-coated plates and peptide-conjugated Sepharose beads. More than 20 peptides promoted cell attachment and five peptides inhibited the biological activity mediated by the recombinant proteins. Some of the peptides were found to interact with integrins and syndecans. These results suggest that the active sites are involved in the biological functions of the laminin α chain G domains. These active peptides may be useful for defining of the molecular mechanism of laminin-receptor interactions and laminin-mediated cellular signaling pathways. Less
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[Publications] Nomizu, M., Yokoyama, F., Suzuki, N., Okazaki, I., Nishi, N., Ponce, M. L., Kleinman, H. K., Yamamoto, Y., Nakagawa, S., Mayumi, T.: "Identification of Homologous Biologically Active Sites on the N-terminal Domain of Laminin Alpha Chains"Biochemistry. 40. 15310-15317 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Utani, A., Nomizu, M,. Matsuura, H., Kato, K., Kobayashi, T., Takeda, U., Aota, S., Nielsen, P. K., Shinkai, H.: "A unique sequence of the laminin alpha 3 G domain binds to heparin and promotes cell adhesion through syndecan-2 and -4"J. Biol. Chem.. 276. 28779-28788 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Makino, M., Okazaki, I., Kasai, S., Nishi, N., Bougaeva, M., Weeks, B. S., Otaka, A., Nielsen, P. K., Yamada, Y., Nomizu, M.: "Identification of Cell Binding Sites in the Laminin α5 Chain G domain"Exp. Cell Res.. 277. 95-106 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kato, K., Utani, A., Suzuki, N., Mochizuki, Yamada, M., Nishi, N., Matsuura, H., Shinkai, H., Nomizu, M.: "Identification of neurite outgrowth promoting sites on the laminin α3 chain G domain"Biochemistry. 41. 10747-10753 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Okazaki, I., Suzuki, N., Nishi, N., Utani, A., Matsuura, H,. Shinkai, H., Yamashita, H., Kitagawa, Y., Nomiuz, M.: "Identification of biologically active sequences in the laminin α4 chain G domain"J. Biol. Chem.. 277. 37070-37078 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamada, M., Kadoya, Y., Kasai, S., Kato, K., Mochizuki, M., Nishi, N., Watanabe, N,. Kleinman, H. K., Yamada, Y., Nomizu, M.: "Ile-Lye-Val-Ala-Val (IKVAV)-containing laminin α1 chain peptides form amyloid-like fibrils"FEBS Letters. 530. 48-52 (2002)
Description
「研究成果報告書概要(欧文)」より
