1997 Fiscal Year Final Research Report Summary
Analysis of TSA-1 that regulates TCR-mediated signal transduction
| Project/Area Number |
08839014
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
免疫の制御機構
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| Research Institution | Osaka University |
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Principal Investigator |
KOSUGI Atsushi Osaka University Medical School, Associate Professor, 医学部, 助教授 (90186685)
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| Project Period (FY) |
1996 – 1997
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| Keywords | T cells / T cell Receptor / TSA-1 / src-family kinases / DIG / CD3zeta / LCK |
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| Research Abstract |
Thymic shared antigen-1 (TSA-1)/stem cell Ag-2 (Sca-2) is a glycosyl-phosphatidylinositol (GPI) -anchored antigen expressed on lymphocytes. We have previously demonstrated that a signal via TSA-1/Sca-2 inhibits T cell receptor (TCR)-medialted T cell activation and apoptosis. To elucidate a molecular mechanism for TSA-1-mediated modulation of the TCR signaling pathway, we examined whether TSA-1 is physically coupled to the TCR in the present study. TSA-1 was clearly associated with CD3zeta chains in T cell hybridomas, activated T cells, and COS-7 cells transfected with TSA-1 and CD3zeta cDNA.The physical association was confirmed on the surface of T cells in immunoprecipitation and confocal microscopy. The analysis using stable and transient transfectants expressing a transmembrane form of TSA-1 revealed that the association of CD3zeta did not require the GPI anchor of TSA-1. Finally, tyrosine phosphorylation of CD3zeta chains was induced after stimulation with anti-TSA-1, suggesting that a functional association between these two molecules also exists. These results imply that the physical association to CD3zeta underlies a regulatory role of TSA-1/Sca-2 in TCR signaling pathway.
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[Publications] Kosugi, A., Saitoh, S.-I., Noda, S., Miyake, K., Yamashita, Y., Kimoto, M., Ogata, M., and Hamaoka, T.: "Physical and functional association between thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2) and the T cell receptor (TCR) complex." J.Biol.Chem.(in press.). (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Kosugi, A., Noda, S., Saitoh, S.-I., Narumiya, S., Ogata, M., Hashimoto, Y., Takase, K., Saito, T.and Hamaoka, T.: "Subunit composition of the pre-T-cell receptor complex analyzed by monoclonal antibody against the pre-T-cell receptor alpha chain." Immunology.91. 618-622 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Abe, Y., Tsutsui, T., Mu, J., Kosugi, A., Yagita, H., Sobue, K., Niwa, O., Fujiwara, H.and Hamaoka, T.: "A defect in cell-to-cell adhesion via integrin-fibronectin interactions in a highly metastatic tumor cell line." Jpn.J.Cancer Res.88. 64-71 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Furuyama, T., Inagaki, S., Kosugi, A., Noda, S., Saitoh, S.-I., Ogata, M., Iwahashi, Y., Miyazaki, N., Hamaoka, T., and Tohyama, M.: "Identification of a novel transmembrane semaphorin expressed on lymphocytes." J.Biol.Chem.271. 33376-33381 (1996)
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「研究成果報告書概要(欧文)」より
