| Project/Area Number |
18590422
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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 |
Bacteriology (including Mycology)
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| Research Institution | Shimane University |
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Principal Investigator |
SHIMIZU Toshiaki Shimane University, Facolty of medicine, Assistant Professor (60284030)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIOKA Haruaki Shimane University, Faculty of medicine, Professor (40034045)
TATANO Yutaka Shimane University, Faculty of medicine, Assistant Professor (70432614)
YASUMOTO Kou Shimane University, Faculty of medicine, Assistant Professor (00448200)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,990,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | mycobacterial infection / Mycobacterium avium complex / suppressor macrophage / T cell / cell-to-cell contact / signal transduction / tyrosine phosphorylation / aldose reductase / Mycobactrium avium complex |
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| Research Abstract |
We previously found that suppressor macrophages (S-Mφs) induced by Mycobacterium avium complex infection affect tyrosine (Tyr) dephosphorylation of several cytoplasmic proteins including aldose reductase (AR) of target T cells with the expression of immunosuppressive activity of S-Mφs. In this study, we examined the profiles of S-Mφ-mediated dephosphorylation of AR in the target T cells and following findings were obtained. (1) Anti-phosphotyrosine antibody bound to AR protein in mouse T cell lysates and recombinant human AR protein (rAR) derived from baculovirus expression system. (2) Since Tyr-40 is located at consensus sequences ([R,K]-x(3)-[D,E]-x(2)-Y) for tyrosine kinase phosphorylation site, Tyr-40 is a candidate for phosphorylation site in mouse AR protein. (3) Anti-phosphoserine antibody also bound to rAR. (4) AR protein was constitutively expressed in resting T cells. In separate experiments, co-cultivation of target T cells with S-Mφs did not cause marked changes in profiles of the expression levels of AR protein in target T cells. (5) Anti-CD3/anti-CD28 monoclonal antibody (mAb)-induced T cell mitogenesis were strongly suppressed by AR inhibitor. In addition, when target T cells were co-cultivated with S-Mφs, anti-CD3/anti-CD28 mAb-induced activation of MAP kinases (Erk-1,-2) in target T cells were not blocked. These findings suggest that AR is not essential for TCR/Ras/Erk signaling pathway in anti-CD3/anti-CD28 mAb-stimulated T cells, whileas AR may be involved in CD28/Akt/NF〓B-mediated signaling pathway in target T cells. Further studies are currently underway to identify protein tyrosine phosphatases which mediate the dephosphorylation of AR in target T cells.
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