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

• 研究課題/領域番号: 13037011
• 研究種目: 特定領域研究
• 配分区分: 補助金
• 審査区分: 生物系
• 研究機関: 東京大学
• 研究代表者: 北村 俊雄 東京大学, 医科学研究所, 教授 (20282527)
• 研究分担者: 野阪 哲哉 東京大学, 医科学研究所, 客員助教授 (30218309)
• 研究期間 (年度): 2001 – 2002
• 研究課題ステータス: 完了 (2002年度)
• 配分額: 4,600千円 (直接経費: 4,600千円); 2002年度: 2,300千円 (直接経費: 2,300千円); 2001年度: 2,300千円 (直接経費: 2,300千円)
• キーワード: Th1 / Th2 / 生物・生体工学 / 遺伝子 / シグナル伝達 / ウイルス

研究概要

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。

研究成果

• [文献書誌] 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)
• [文献書誌] Tulin, E.E.: "Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H+-ATPAse-like protein"Oncogene. 21. 844-848 (2002)
• [文献書誌] 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)
• [文献書誌] Perez, O.D.: "Acitivation of the PKB/AKT pathway by ICAM-2"Immunity. 16. 51-65 (2002)
• [文献書誌] Nagai, Y.: "Essential role of MD-2 in LPS responsiveness and TLR4 distribution"Nat. Immunol.. 3. 667-672 (2002)
• [文献書誌] 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)
• [文献書誌] Stoeclin, G.: "Functional cloning of BRF-1, a regulator of ARE-dependent mRNA turnover"EMBO J.. 21. 4709-4718 (2002)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] Yujiri, T.: "MEK kinase 1 interacts with focal adhesion kinase and regulates insulin receptor substrate-1 expression"J. Biol. Chem.. (in press). (2003)
• [文献書誌] 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)
• [文献書誌] Nosaka, T.: "Dwarfism and lymphoid deficiency in mice lacking twisted gastrulation"Mol. Cell. Biol.. (in press). (2003)
• [文献書誌] Kitamura, T.: "Retrovirus-mediated gene transfer and expression cloning, powerful tools in functional genomics"Exp. Hematol.. (in press). (2003)
• [文献書誌] Kagami, S.: "Role of Stat5a in T Helper Cell Differentiation"Blood. 97. 2358-2365 (2001)
• [文献書誌] Hirose, K.: "MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody"J.Biol.Chem.. 276. 5821-5828 (2001)
• [文献書誌] Kamizono, S.: "The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2"J.Biol.Chem.. 276. 12530-12538 (2001)
• [文献書誌] 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)
• [文献書誌] Tonozuka, Y: "Molecular cloning of a human novel type I cytokine receptor related to Delta1"Cytogenetics and Cell Genetics. 93. 23-25 (2001)
• [文献書誌] Ishido, M.: "Cholesterol requirement for receptor transport from multivesicular late endosomes to the Golgi"J.Cell Science. 114. 1965-1976 (2001)
• [文献書誌] 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)
• [文献書誌] Kimura, M.: "Regulation of Th2 cell differentiation by mel-18, a mammalian polycomb group gene"Immunity. 15. 275-287 (2001)
• [文献書誌] Senga, T.: "JAK/Stat3 dependent activation of RalGDS/Ral pathway in M1 mouse myeloid leukemic cells"J.Biol.Chem.. 276. 32678-32681 (2001)
• [文献書誌] Frasor, J.: "Differential roles for Stat5α and Stat5β in prolactin stimulation of estrogen receptor a and b transcription"Molecular Endcrinol. 15. 2172-2181 (2001)
• [文献書誌] Yamamoto, S.: "Proleferation of parenchymal neural progenitors in response to injury in the adult rat spinal cord"Exp.Neurol.. 172. 115-127 (2001)
• [文献書誌] 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)
• [文献書誌] Yamashita, Y: "Sak serine-threonine kinase acts as an effector of Tec tyrosine kinase"J.Biol.Chem.. 276. 39012-39020 (2001)
• [文献書誌] 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)
• [文献書誌] Ye, S.K.: "The IL-7 receptor controls the accessbility of the TCRγ locus by Stat5 and histone acetylation"Immunity. 15. 813-823 (2001)
• [文献書誌] Yamamoto, S.: "Transcription factor expression and Notch-dependent regulation of neural progenitors in the adult rat spinal cord"J.Neurosci.. 21. 9814-9823 (2001)
• [文献書誌] 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)
• [文献書誌] Arakawa, M.: "Negamycin can restore dystrophin in mdx sskeletal muscle"Acta Myologica. 20. 154-158 (2001)
• [文献書誌] 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)
• [文献書誌] Tulin, E.E.: "Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H+-ATPAse-like protein"Oncogene. (in press).
• [文献書誌] 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).
• [文献書誌] 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).
• [文献書誌] Perez, O.D.: "Acitivation of the PKB/AKT pathway by ICAM-2"Immunity. 16. 51-65 (2002)