| Project/Area Number |
10044288
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Kobe University |
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Principal Investigator |
MINAMI Yasuhiro KOBE UNIVERSITY, SCHOOL OF MEDICINE, Professor, 医学部, 教授 (70229772)
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| Co-Investigator(Kenkyū-buntansha) |
KOSUGI Atsushi Osaka University, School of Medicine, Associate Professor, 医学部, 助教授 (90186685)
OGATA Masato Osaka University, School of Medicine, Research associate, 医学部, 助手 (60224094)
OTANI Hiroki Shimane Medical University, Professor, 医学部, 教授 (20160533)
UMEHARA Hisanori Osaka Dental University, Lecturer, 歯学部, 講師 (70247881)
TANAKA Yosiya University of Occupational and Environmental Health School of Medicine, Lecturer, 医学部, 講師 (30248562)
SAMELSON L.E 米国国立衛生研究所, 部長
O'SHEA J.J. 米国国立衛生研究所, 部長
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 1999: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1998: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Keywords | lymphocytes / signal transduction / protein tyrosine kinase / protein tyrosine phosphatases / adaptors / protooncogene products / cell adhesion / チロシンリン酸化 / 子宮外発生法 / T細胞受容体 |
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| Research Abstract |
In this study, we have found that the proto-oncogene products, H-Ras and c-Myc, act co-operatively to induce homophilic cell adhesion of lymphocytes through the induction of VLA-4 activation and of VCAM-1 expression (Minami, Tanaka). It was also shown that Syk tyrosine kinase and SHP-2 tyrosine phosphatase play important roles in IL-2-induced signal transduction (O'Shea). It was found that an adaptor molecule, LAT is palmitoylated and sequestered at GEM, and is required for the development and activation of T lymphocytes (Samelson). An importance of GEM in T cell engagement was also elucidated (Kosugi). In this study, we have established an experimental system using exo utero method, aiming to examine the effects of tyrosine kinase/phosphatase inhibitors on lymphocyte development in vivo (Otani). We have also shown that a lymphocyte-specific tyrosine phosphatase, LC-PTP, inhibits ERK that is activated during T cell activation (Ogata). It was reported that topoisomerase II inhibitors induce apoptosis of lymphocytes. In this study, it was found that Lyn tyrosine kinase regulates positively the topoisomerase II inhibitor-induced apoptosis of lymphocytes (Yamamura). We have also examined a possible role of tyrosine phosphatases in the process of lymphocyte-macrophage interaction (Moriyama). It was shown that engagement of LFA-1 and of TCR results in a synergistic tyrosine phosphorylation of Fak tyrosine kinase (Umehara). In this collaborative study, we have exchanged results mutually, and have discussed about the respective results extensively. We have also discussed to plan our future collaborative experiments.
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