2002 Fiscal Year Final Research Report Summary
Functional roles of PI3 Kinase in immune system
| Project/Area Number |
13670322
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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 University School of Medicine, Asspciate Professor, 医学部, 助教授 (70235985)
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| Project Period (FY) |
2001 – 2002
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| Keywords | PI3K / P85α / Btk / knockout mice / signal transduction / NF-kB / Akt / bcl-xL |
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| Research Abstract |
Mice deficient for p85α regulatory subunit of PI3-kinase showed impaired B cell development and activation, and their phenotype was nearly identical to that of Btk-/- mice. Since phosphatidylinositol-(3,4,5) triphosphate, a major product of PI3-kinases has been proposed to play a critical role in membrane recruitment and activation of Btk, phenotypic resemblance of these two knockout mice seemed to reveal direct functional association between PI3-K and Btk. However, BCR-induced activation of Btk in mouse B cells was unaffected by PI3K inhibitors or by the lack of phosphoinositide-3 kinase (PI3K). Consistent with this observation, PI3K/Btk double deficient mice show more severe defects than either single knockout mouse. Activation of NF-kB and induction of Bcl-x_L and cyclin D2 were severely blocked in both PI3K^<-/-> and Btk^<-/-> single deficient B cells and transgenic expression of Bcl-x_L restored the development and BCR-induced proliferation of B cells in PI3K^<-/-> mice. Our results collectively indicate that PI3K and Btk have unique roles in proximal BCR signaling, and they have a common target further downstream in the activation of NF-kB.
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Research Products
(10 results)
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[Publications] Harumi Suzuki, Satoshi Matsuda, Yasuo Terauchi, Mari Fujiwara, Toshiaki Ohteki, Tomoichiro Asano, Timothy W. Behrens, Taku Kouro, Kiyoshi Takatsu, Takashi Kadowaki, Shigeo Koyasu: "PI3K and Btk differentially regulate B cell antigen receptor-mediated signal transduction"Nature Immunol. 4. 280-286 (2003)
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[Publications] Kazunaga Agematsu, Takeshi Futatani, Sho Hokibara, N Kobayashi, Masaya Takamoto, Satoshi Tsukada, Harumi Suzuki, Shigeo Koyasu, Toshio Miyawaki, Kazuo Sugane, Atsushi Komiyama, Hans D Ochs: "Absence of memory B cells in patients with common variable immunodeficiency"Clin. Immunol.. 103. 34-42 (2002)
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