2001 年度実績報告書

サイトカイン作用の多様性とSTAT5

研究課題

研究課題/領域番号	13470070
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)
キーワード	サイトカイン / シグナル伝達 / START5 / IL6 / NFKB
研究概要	レトロウイルスによる発現スクリーニング法にPCRによる任意点変異導入法を組み合わせて同定した恒常的活性型STAT5(Onishi et al. Mal Cell Biol, 1998 ; Ariyoshi et al. J.Biol Chem, 2000)を利用してサイトカインの多様な作用のメカニズムを研究している。STAT5はさまざまな遺伝子の発現を誘導することが知られているが我々は以前に恒常的活性型STAT5を利用した実験によってSTAT5がpin-1、socs-1、p21の発現誘導を介して同じ細胞において増殖、アポトーシス、分化誘導という多彩な作用を有することを示した(Nosaka et al. EMBO J, 1999)。今回、我々は恒常的活性型STAT5がM1細胞のマクロファージ系への分化を誘導するメカニズムを解析してSTAT5の下流でIL-6の発現が誘導されオートクライン機構を介してM1細胞の分化を誘導することを示した(Kawashima et al. J. Immunol, 2001)。興味深いことにIL-6遺伝子の発現誘導はNFKB活性化を介していることが判明した。さらにこのメカニズムを解析中であるが現在までにSTAT5活性化により誘導される分泌蛋白質により二次的にIL-6発現が誘導されることが明らかになった(Nakamura et al. J Biol Chem, 2002)。

研究成果
(23件)

すべてその他

すべて文献書誌 (23件)

[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] Ishida, 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 from 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] Tulin, 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+-ATPAdse-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)

2001 年度 実績報告書

サイトカイン作用の多様性とSTAT5

研究代表者

北村 俊雄 東京大学, 医科学研究所, 教授 (20282527)

研究成果

[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] Ishida, 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 from 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] Tulin, 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+-ATPAdse-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)

2001 年度実績報告書

北村俊雄東京大学, 医科学研究所, 教授 (20282527)