Project/Area Number |
09670339
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Immunology
|
Research Institution | KUMAMOTO UNIVERSITY |
Principal Investigator |
INUI Seiji Kumamoto University, School of Medicine, Associate Professor, 医学部, 助教授 (70243384)
|
Project Period (FY) |
1997 – 1998
|
Project Status |
Completed (Fiscal Year 1998)
|
Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
Keywords | B cell / signal transduction / alpha4 / protein phosphatase 2A / immunosuppressant / rapamycin / gene targeting / a4 / リンパ細胞 / 遺伝子ターゲティング / 抗原レセプター |
Research Abstract |
A novel signal transducer alpha4 was originally found as a molecule involved in B cell antigen receptor signal transduction. During the functional analysis, we found that alpha4 is associated with the catalytic subunit of phosphatase 2A (PP2Ac). Interaction of alpha4 with PP2Ac was direct and independent of regulatory molecules. Middle region of alpha4 was necessary and sufficient for interaction with PP2Ac. An immunosuppressant rapamycin treatment disrupts the association of PP2 Ac/alpha4 in parallel with the inhibitory effect of lymphoid cell proliferation. Rapamycin treatment also suppresses the phosphatase activity of cells. Introduction of the mouse alpha4 cDNA into Jurkat cells confers rapamycin resistance. Moreover, alpha4 augments the PP2A activity in the in vitro assay. These results suggest that alpha4 acts, as a positive regulator of PP2A and as a new target of rapamycin, in activation of lymphocytes. To analyze the in vivo function of alpha4, we have been trying to knock out the alpha4 gene using Cre/lox P system. Genomic gene of murine alpha4 was cloned and a vector for gene targeting was constructed.
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