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Th2細胞優位に発現されるサイトカインレセプターδ1の解析

Research Project

Project/Area Number 13037011
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

北村 俊雄  東京大学, 医科学研究所, 教授 (20282527)

Co-Investigator(Kenkyū-buntansha) 野阪 哲哉  東京大学, 医科学研究所, 客員助教授 (30218309)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsTh1 / Th2 / 生物・生体工学 / 遺伝子 / シグナル伝達 / ウイルス
Research Abstract

我々は自ら開発したシグナルシークエンストラップ法SST-REX(Kojima and Kitamura, Nat Biotech, 1999)を利用してTh2細胞優位に発現しているマウス新規サイトカインレセプターδ1を同定した(Fujio et al. Blood, 2001)。その後δ1がTSLP(Thymic Stroma Lymph opoietein)というサイトカインのレセプターのサブユニットであることが判明した。δ1がIL7レセプターとヘテロダイマーを形成し機能性TSLPレセプターを形成する。δ1がIL2/IL4/IL7/IL9/IL15レセプターの共通のサブユニットである共通γ鎖と相同性を有することから、他のサイトカインのレセプターにも関与している可能性を考え検索を行っているが現在までにこの可能性を示唆するデータは得られていない。米国NIHグループとの共同研究でδ1/TSLPレセプターのノックアウトマウスを作製したが現在までのところ胸腺がやや小さい以外は目立った表現型は見つかっていない。ヒトでもδ1/TSLPレセプターと構造上の類似性を有するサイトカインレセプターのcDNAを単離したが、遺伝子座はXYの偽常染色体上のGM-CSFレセプターおよびIL-3レセプターαサブユニットの近傍に存在することが判明した(Tonozuka et al. Cytogenet and Cell Genet, 2001)。今後、最近作製したマウスδ1に対するモノクローナル抗体を利用して種々の細胞における発現を調べる予定である。

Report

(2 results)
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Tulin, E.E.: "Genetic approach and phenotype-based complementation screening for identification of stromal cell-derived proteins involved in cell proliferation"Exp. Cell Res.. 272. 23-31 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tulin, E.E.: "Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H+-ATPAse-like protein"Oncogene. 21. 844-848 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nosaka, T.: "Pim-1 expression is sufficient to induce cytokine independence in murine hematopoietic cells, but is dispensable for BCR-ABL-mediated transformation"Exp. Hematol.. 30. 697-702 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Perez, O.D.: "Acitivation of the PKB/AKT pathway by ICAM-2"Immunity. 16. 51-65 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagai, Y.: "Essential role of MD-2 in LPS responsiveness and TLR4 distribution"Nat. Immunol.. 3. 667-672 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Gugasyan, R.: "Dok-related protein negatively regulates T cell development its RasGTPase-activating protein and Nck docking sites"J. Cell Biol.. 158. 115-125 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Stoeclin, G.: "Functional cloning of BRF-1, a regulator of ARE-dependent mRNA turnover"EMBO J.. 21. 4709-4718 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Komano, H.: "A new functional screening system for the identification of DNA encoding a regulator of γ-cleavage"J. Biol. Chem.. 277. 39627-39633 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ezoe, S.: "GATA-2 affects cytokine-dependent growth of hematopoietic cells through-accumulation of p21^<WAF1> and p27^<Kip1> proteins"Blood. 100. 3512-3520 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yujiri, T.: "MEK kinase 1 interacts with focal adhesion kinase and regulates insulin receptor substrate-1 expression"J. Biol. Chem.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Minoshima, Y.: "Aurora B Phosphorylates MgcRacGAP and Induces RhoGAP Activity during M phase : Identification of a RhoGAP Indispensable for Cytokinesis"Developmental Cell. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nosaka, T.: "Dwarfism and lymphoid deficiency in mice lacking twisted gastrulation"Mol. Cell. Biol.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitamura, T.: "Retrovirus-mediated gene transfer and expression cloning, powerful tools in functional genomics"Exp. Hematol.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kagami, S.: "Role of Stat5a in T Helper Cell Differentiation"Blood. 97. 2358-2365 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirose, K.: "MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody"J.Biol.Chem.. 276. 5821-5828 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kamizono, S.: "The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2"J.Biol.Chem.. 276. 12530-12538 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawashima, T.: "STAT5 induces macrophage differentiation of M1 leukemia cells through activation of IL-6 production mediated by NF-κB p65"J.Immunol.. 167. 3652-3660 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tonozuka, Y: "Molecular cloning of a human novel type I cytokine receptor related to Delta1"Cytogenetics and Cell Genetics. 93. 23-25 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishido, M.: "Cholesterol requirement for receptor transport from multivesicular late endosomes to the Golgi"J.Cell Science. 114. 1965-1976 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tulin, E.E.: "A novel secreted form of immune suppressor factor with high homology to vacuolar ATPase identified by forward genetic approach of functional screening based on cell proliferation"J.Biol.Chem.. 276. 27519-27526 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kimura, M.: "Regulation of Th2 cell differentiation by mel-18, a mammalian polycomb group gene"Immunity. 15. 275-287 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Senga, T.: "JAK/Stat3 dependent activation of RalGDS/Ral pathway in M1 mouse myeloid leukemic cells"J.Biol.Chem.. 276. 32678-32681 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Frasor, J.: "Differential roles for Stat5α and Stat5β in prolactin stimulation of estrogen receptor a and b transcription"Molecular Endcrinol. 15. 2172-2181 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto, S.: "Proleferation of parenchymal neural progenitors in response to injury in the adult rat spinal cord"Exp.Neurol.. 172. 115-127 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tokoro, Y.: "Molecular cloning and characterization of mouse tspan-3, a novel member of the tetraspanin superfamily, expressed on resting dendritic cells"Biochem.Biophys.Res.Commun.. 288. 178-183 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamashita, Y: "Sak serine-threonine kinase acts as an effector of Tec tyrosine kinase"J.Biol.Chem.. 276. 39012-39020 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ueno, M.: "Identification of an embryonic dorsal aorta specific gene, endomucin, and its inhibitory activity on cell adhesion"Biochem.Biophys.Res.Commun.. 287. 501-506 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ye, S.K.: "The IL-7 receptor controls the accessbility of the TCRγ locus by Stat5 and histone acetylation"Immunity. 15. 813-823 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto, S.: "Transcription factor expression and Notch-dependent regulation of neural progenitors in the adult rat spinal cord"J.Neurosci.. 21. 9814-9823 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Thlin, E.E.: "SF20, a novel bone marrow stroma-derived factor that binds to mouse TSA-1 and supports lymphoid cell proliferation"J.Immunol.. 167. 6338-6347 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Arakawa, M.: "Negamycin can restore dystrophin in mdx sskeletal muscle"Acta Myologica. 20. 154-158 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tulin, E.E.: "Genetic approach and phenotype-based complementation screening for identification of stromal cell-derived proteins involved in cell proliferation"Exp.Cell Res.. 272. 23-31 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tulin, E.E.: "Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H+-ATPAse-like protein"Oncogene. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakamura, T.: "Cytokine receptor common β subunit-mediated STAT5 activation confers NFκB activation through IκB-independent mechanism in a murine pro B cell line Ba/F3"J.Biol.Chem.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Kitamura, T.: "Role of MgcRacGAP/CYK4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation"Cell Structure and Function. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Perez, O.D.: "Acitivation of the PKB/AKT pathway by ICAM-2"Immunity. 16. 51-65 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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