2001 Fiscal Year Annual Research Report

サイトカイン作用の多様性とSTAT5

Research Project

Project/Area Number	13470070
Research Institution	The 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)
Keywords	サイトカイン / シグナル伝達 / START5 / IL6 / NFKB
Research Abstract	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)。

Research Products

(23 results)

All Other

All Publications (23 results)

[Publications] Kagami, S.: "Role of Stat5a in T Helper Cell Differentiation"Blood. 97. 2358-2365 (2001)
[Publications] Hirose, K.: "MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody"J.Biol.Chem.. 276. 5821-5828 (2001)
[Publications] Kamizono, S.: "The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAk2"J.Biol.Chem.. 276. 12530-12538 (2001)
[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)
[Publications] Tonozuka, Y.: "Molecular cloning of a human novel type I cytokine receptor related to Delta1"Cytogenetics and Cell Genetics. 93. 23-25 (2001)
[Publications] Ishida, M.: "Cholesterol requirement for receptor transport from multivesicular late endosomes to the Golgi"J.Cell Science.. 114. 1965-1976 (2001)
[Publications] 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)
[Publications] Kimura, M.: "Regulation of Th2 cell differentiation by mel-18, a mammalian polycomb group gene"Immunity. 15. 275-287 (2001)
[Publications] Senga, T.: "JAK/Stat3 dependent activation of RalGDS/Ral pathway in M1 mouse myeloid leukemic cells"J.Biol.Chem.. 276. 32678-32681 (2001)
[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)
[Publications] Yamamoto, S.: "Proleferation of parenchymal neural progenitors in response to injury in the adult rat spinal cord"Exp.Neurol. 172. 115-127 (2001)
[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)
[Publications] Yamashita, Y.: "Sak serine-threonine kinase acts as an effector of Tec tyrosine kinase"J.Biol.Chem. 276. 39012-39020 (2001)
[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)
[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)
[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)
[Publications] 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)
[Publications] Arakawa, M.: "Negamycin can restore dystrophin in mdx sskeletal muscle"Acta Myologica. 20. 154-158 (2001)
[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)
[Publications] Tulin, E.E.: "Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H+-ATPAdse-like protein"Oncogene. (in press).
[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).
[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).
[Publications] Perez, O.D.: "Acitivation of the PKB/AKT pathway by ICAM-2"Immunity. 16. 51-65 (2002)

2001 Fiscal Year Annual Research Report

サイトカイン作用の多様性とSTAT5

Principal Investigator

北村 俊雄 東京大学, 医科学研究所, 教授 (20282527)

Research Products

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

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

[Publications] Kamizono, S.: "The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAk2"J.Biol.Chem.. 276. 12530-12538 (2001)

[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)

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

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

[Publications] 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)

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

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

[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)

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

[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)

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

[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)

[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)

[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)

[Publications] 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)

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

[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)

[Publications] Tulin, E.E.: "Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H+-ATPAdse-like protein"Oncogene. (in press).

[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).

[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).

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

北村俊雄東京大学, 医科学研究所, 教授 (20282527)