| Project/Area Number |
09670331
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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 |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKAI Satoshi The University of Tokyo, Institute for Medical Science, Research Associate, 医科学研究所, 助手 (10242116)
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| Co-Investigator(Kenkyū-buntansha) |
TAKETSU Kiyoshi The University of Tokyo, Institute for Medical Science, Professor, 医科学研究所, 教授 (10107055)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Adaptor protein / Lnk / B cell development / Lymphocyte development / Signal transduction / リンパ球 / B細胞 / 細胞内蛋白質 / ノックアウトマウス |
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| Research Abstract |
Lnk is an intracellular adaptor protein expressed in lymphocytes with a single SH2 domain. Previously, Lnk protein was shown to become tyrosine phosphorylated after T-cell receptor (TCR) crosslinking and appeared to interact with Grb2, PLC-gl and PI3K as judged by coimmunoprecipitation. These observations suggested that Lnk could be involved in signaling through TCR.To understand the function of Lnk in mice, we have generated the transgenic mice expressing Lnk at very high levels in thymocytes and the Lnk-deficient mice by homologous recombination in embryonic stem cells.
Thymocytes from transgenic mice proliferated normally and showed an equivalent pattern of tyrosine phosphorylated proteins when compared with normal thymocytes stimulated via TCR crosslinking.
Lnk-deficient mice develop normally and grow equivalently as littermate control mice. To our surprise, T cells developed normally in Lnk-deficient mice. On the other hand, B lymphopoiesis was strongly enhanced in Lnk-/- mice. Spleen contained pre-B cells and increased number of immature B cells freshly emigrated from bone marrow. In bone marrow, pro-B cells significantly increased and B-lineage cells were proportionally expanded thereafter. The B cell accumulation was caused by enhanced production of pro-B cells, but not by prolonged survival, consequent of intrinsic defects of B ceIl precursors. These results demonstrate a regulatory function of Lnk in controlling B cell production. Our results also illustrated a possible function of a new family of adaptor proteins represented by Lnk which may negatively control mitogenic signals.
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