2004 Fiscal Year Final Research Report Summary
Function of Rac1 in T cell development and activation
| Project/Area Number |
15590440
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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 | Yamaguchi University |
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Principal Investigator |
SUZUKI Harumi Yamaguchi Univ., Sch.Med., Dept.Microbiology, Associate prof., 医学部, 助教授 (70235985)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Rac / T cell development / selection / bcl-2 / thymus / signal transduction / apoptosis / pro B cell |
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| Research Abstract |
Rac1, one of the Rho family small GTPases has been shown to work as a "molecular switch" in various signal transduction pathways. In order to directly assess the function of Rac1 in T cell development, we introduced dominant negative (dn) Rac1 gene into Pax5-deficient mouse pro-B cells, which can reconstitute T cell development in vivo. Differentiation of GFP positive dnRac1 expressing thymocytes into CD4- and CD8-single positive (SP) cells was severely impaired, indicating that Rac1 is critical in positive selection of thymocytes. Thymocytes expressing dnRac1 demonstrated increased apoptosis against TCR stimulation. In order to study detailed function of Rac1 in TCR signal transduction of DP thymocytes, we utilized DP cell line DPK, which can differentiate into CD4-SP cells upon TCR stimulation in vitro. DPK expressing dn-Rac1 underwent massive apoptosis upon TCR stimulation and resulted in defective differentiation of CD4-SP cells. TCR dependent actin polymerization and upregulation of Bcl-2 transcription were suppressed in dnRac1-DPK. Collectively, these data indicate that Rac1 is critical in positive selection of thymocyte through not only reorganizing actin cytoskeleton, but also preventing TCR-induced apoptosis via Bcl-2 upregulation.
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Research Products
(6 results)
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[Journal Article] Functional phenotype of phosphoinositide 3-kinase p85a null platelets characterized by an impaired response to GP VI stimulation2003
Author(s)
Naohide Watanabe, Hideaki Nakajima, Hidenori Suzuki, Atsushi Oda, Yumiko Matsubara, Masaaki Moroi, Takashi Kadowaki, Harumi Suzuki, Shigeo Koyasu, Yasuo Ikeda, Makoto Handa
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] PI3K and Btk differentially regulate B cell antigen receptor-mediated signal transduction2003
Author(s)
Harumi Suzuki, Satoshi Matsuda, Yasuo Terauchi, Mari Fujiwara, Toshiaki Ohteki, Tomoichiro Asano, Timothy W.Behrens, Taku Kouro, Kiyoshi Takatsu, Takashi Kadowaki, Shigeo Koyasu
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Journal Title
Nature Immunol. 4
Pages: 280-286
Description
「研究成果報告書概要(欧文)」より
