2000 Fiscal Year Final Research Report Summary
GD3 Ganglioside, Expression, Modification and its Biological Function
| Project/Area Number |
10480173
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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 |
Functional biochemistry
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| Research Institution | TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH |
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Principal Investigator |
SANAI Yutaka Tokyo Metropolitan Institute of medical Science, Researcher, 東京都臨床医学総合研究所, 研究員 (40150289)
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| Co-Investigator(Kenkyū-buntansha) |
TAJIMA Youich Tokyo Metropolitan Institute of medical Science, Researcher, 東京都臨床医学総合研究所, 研究員 (00300955)
KASAHARA Kohji Tokyo Metropolitan Institute of medical Science, Researcher, 東京都臨床医学総合研究所, 研究員 (60250213)
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| Project Period (FY) |
1998 – 2000
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| Keywords | ganglioside / tyrosine kinase / cell adhesion molecule / signal transduction / raft / caveolae |
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| Research Abstract |
The association of ganglioside GD3 with TAG-1, a glycosylphosphatidylinositol-anchored neuronal cell adhesion molecule, was examined by coimmunoprecipitation experiments. Previously, we have shown that the anti-ganglioside GD3 antibody (R24) immunoprecipitated the Src family kinase Lyn from the rat cerebellum, and R24 treatment of primary cerebellar cultures induced Lyn activation and rapid tyrosine phosphorylation of an 80-kDa protein (p80). We now report that R24 coimmunoprecipitates a 135-kDa protein (p135) from primary cerebellar cultures. Treatment with phosphatidylinositol-specitic phospholipase C revealed that p135 was glycosylphosphatidylinositol-anchored to the membrane. It was identified as TAG-1 by sequential immunoprecipitation with an anti-TAG-1 antibody. Antibody-mediated cross-linking of TAG-1 induced Lyn activation and rapid tyrosine phosphorylation of p80. Selective inhibitor for Src family kinases reduced the tyrosine phosphorylation of p80. Sucrose density gradient analysis revealed that the TAG-1 and tyrosine-phosphorylated p80 in cerebellar cultures were present in the lipid raft fraction. These data show that TAG-1 transduces signals via Lyn to p80 in the lipid rafts of the cerebellum. Furthermore, degradation of cell-surface glycosphingolipids by endoglycoceramidase induced an alteration of TAG-1 distribution on an OptiPrep gradient and reduced the TAG-1-mediated Lyn activation and tyrosine phosphorylation of p80. These observations suggest that glycosphingolipids are involved in TAG-1-mediated signaling in lipid rafts.
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[Publications] Kanai,Y..Kanai-Azuma,M.,Tajima,Y.,Birk,O.S.,Hayashi,Y.,Sanai.Y.: "Identification of a stromal cell type characterized by the secretion of a soluble integrin-binding protein, MFG-E8, in mouse early gonadogenesis."Mech Dev.96, 223-227, (2000). 96. 233-227 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kasahara,K.,Watanabe,K.,Takeuchi,K.,Kaneko,H.,Oohira,A.,Yamamoto,T.,Sanai,Y.: "Involvement of gangliosides in GPI-anchored neuronal cell adhesion molecule TAG-1 signaling in lipid rafts"J.Biol.Chem.275(44) 34701-34709, 2000. 275. 34701-34709 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Goldberg,G.S.,Tajima,Y.,Merritt.M.,Omori,Y.,Gawinowicz,M.A.,Sanai,Y.: "Connexicin43 suppresses MFG-E8 while induction contact growth inhibition of glioma."Cancer Research. 60. 6018-6029 (2000)
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「研究成果報告書概要(和文)」より
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[Publications] Ishii, A., Ohta, M., Watanabe, Y., Matsuda, K., Ishiyama, K., Sakoe, K., Nakamura, M., Inokuchi, J., Sanai, Y., and Saito, M.: "Expression cloning and functional characterization of human cDNA for ganglioside GM3 synthase."J.Biol. Chem.. 273. 31652-31655 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Shimoda, Y., Tajima, Y., nagase, T., Harii, K., Osumi, N.and Sanai, Y.: "Cloning and Expression of a Novel Galactoside β1, 3-Glucruronyltransferase involved in the Biosynthesis of HNK-1 Epitope"J.Biol. Chem.. 274. 17115-17122 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Kanai, Y., Kanai-Azuma, M., Tajima, Y., Birk, O.S., Hayashi, Y., Sanai, Y.: "Identification of a stromal cell type characterized by the secretion of a soluble integrin-binding protein, MFG-EB, in mouse early gonadogenesis."Mech Dev.. 96. 223-227 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Goldberg, G.S., Bechberger, J.F., Tajima, Y., merritt, M., Omori, Y., Gawinowicz, M.A., Narayanan, R., Tan, Y., Sanai, Y., Yamasaki, H., Naus, C.C.G., Tsuda, H., Nicholson, B.J.: "Connexicin43 suppresses MFG-EB while induction contact growth inhibition of glioma."Cancer Research. 60. 6018-6026 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kasahara, K., Watanabe, K., Takeuchi, K., Kaneko, H., Oohira, A., Yamamoto, T., Sanai, Y.: "Involvement of gangliosides in GPI-anchored neuronal cell adhesion molecule TAG-1 signaling in lipid rafts."J.Biol. Chem.. 275 (44). 34701-34709 (2000)
Description
「研究成果報告書概要(欧文)」より
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