Regulation of lymphocyte phospholipase C activity by a low molecular weight GTP-binding protein and its physiological role
| Project/Area Number |
02670990
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | University of Tokyo |
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Principal Investigator |
TOYOSHIMA Satoshi University of Tokyo, Faculty of Pharmaceutical Sciences, Associated Professor, 薬学部, 助教授 (40092283)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1991: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1990: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Phospholipase C / Butulinum ADP-ribosyltransferase / Lymphocyte activation / T cell antigen receptor / MRL / lpr mouse / low molecular weight GTP-binding protein / ボツリヌスADPーリボシルトランスフェラ-ゼ / lprマウス / イノシト-ルリン脂質 |
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| Research Abstract |
As reported previously, there is a low molecular weight GTP-binding protein(G21K)in calf thymocytes which is associated with not only physically but also functionally with soluble phosphoinositide-specific phospholipase C(PLC). In the present study, its physiological role was investigated and following results were obtained.
1. G21K was found to be ADP-ribosylated by ADP-ribosyltransferase from Clostridum botulinum type C strain and ^<32>P -ADP-ribosylated G21K was easily identified on two dimensional gel electrophoresis.
2. G21K was also detected in mouse thymocytes.
3. Botulinum ADP-ribosyltransferase induced an increase of inositol phosphates(PLC)formation in mouse thymocyte membranes. Incubation of electropermeabilized mouse thymocytes with the enzyme also caused an inprease of IPs formation in the cells. These results suggest that the stimulation of PLC was related to ADP-ribosylation of G21K by the enzyme.
4. G21K was found to be associated with T cell antigen receptor(TCR)/CD3 complex in mouse thymocytes. This result suggests that G21K plays some important role in the T cell activation pathway via TCR/CD3 complex.
5. It was found that very little amounts of G21K were associated with Con A receptor in T cells of autoimmune model mouse, MRL/Ipr. As reported previously, MRL/Ipr T cells hardly respond to Con A and an increase of phosphoinositide turnover is not observed in MRL/Ipr T cells stimulated with Con A. However, Con A binding to the receptor is normal and stimulation of G-protein by GTPYS induces PLC activation. These results suggest that the coupling of Con A-receptor and the G-protein is abnormal.
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Report
(3 results)
Research Products
(18 results)
