2001 年度実績報告書

マスト細胞の不活性化に関与する分子の同定

研究課題

研究課題/領域番号	13557040
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)
キーワード	マスト細胞 / シグナルシークエンストラップ / 膜蛋白質 / シグナル伝達 / アレルギー
研究概要	マスト細胞の不活化の分子メカニズムは、活性化のメカニズムに較べてほとんど解析が進んでいない。そこで我々は刺激前の定常状態および刺激後期(1〜2時間後)の細胞から抽出したmRNAを利用してシグナルシークエンストラップを行ない、マスト細胞の活性化の調節に関与する膜蛋白質あるいは分泌蛋白質を同定することを試みた。シグナルシークエンストラップは、我々が独自に開発したレトロウイルスベクターを利用した方法SST-REXを利用した。マウス骨髄由来培養マスト細胞の定常状態および刺激1〜2時間後のSSTライブラリーを作成しスクリーニングの結果得られた計2,000クローンうち95%以上のクローンがシグナルシークエンスを有するcDNAで膜蛋白質あるいは分泌蛋白質をコードしていると考えられた。約10%のクローンはest以外に通常のデータベ-スにはない未知のcDNAであった。未知のクローンの中では、細胞内に免疫シグナル抑制モチーフ(ITIM)を有するNK細胞受容体様分子(MASTIR)と未知の7回膜貫通型分子に注目して研究を進めている。現在までに、MASTIRにはその細胞外ドメインに相同性を有する分子MASTARが存在すること、MASTIRがチロシンフォスファターゼSHP1およびSHP2との会合を介しておそらく負のシグナルを伝えるのに対して、MASTARはDAP10およびDAP12という膜蛋白質と会合し細胞内に正のシグナルを伝えることを明らかにした。現在、マスト細胞活性化におけるMASTARおよびMASTIRの役割を明らかにするためにノックアウトマウスの作成も含め研究を進めている。

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"Cytogeneties 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 diffrentiation 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 charcterization 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. Biopbys. 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. 99814-9823 (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.: "Gnetic 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 ShIR, a vacuolar H+-ATPAse-like protein"Oncogene. (in press).
[文献書誌] Nakamura, T.: "Cytokine receptor common β subunit-mediated STAT5 a activation confers NFκB activation through IkB-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

マスト細胞の不活性化に関与する分子の同定

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"Cytogeneties 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 diffrentiation 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 charcterization 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. Biopbys. 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. 99814-9823 (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.: "Gnetic 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 ShIR, a vacuolar H+-ATPAse-like protein"Oncogene. (in press).

[文献書誌] Nakamura, T.: "Cytokine receptor common β subunit-mediated STAT5 a activation confers NFκB activation through IkB-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)