2001 Fiscal Year Annual Research Report

マスト細胞の不活性化に関与する分子の同定

Research Project

Project/Area Number	13557040
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)
Keywords	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
Research Abstract	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。

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"Cytogeneties and Cell Genetics. 93. 23-25 (2001)
[Publications] Ishido, 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 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)
[Publications] Kimura, M.: "Regulation of Th2 cell diffrentiation 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 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)
[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. Biopbys. 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. 99814-9823 (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.: "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)
[Publications] Tulin, E.E.: "Inhibition of human endothelial cell proliferation by ShIR, a vacuolar H+-ATPAse-like protein"Oncogene. (in press).
[Publications] 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).
[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

マスト細胞の不活性化に関与する分子の同定

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"Cytogeneties and Cell Genetics. 93. 23-25 (2001)

[Publications] Ishido, 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 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)

[Publications] Kimura, M.: "Regulation of Th2 cell diffrentiation 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 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)

[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. Biopbys. 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. 99814-9823 (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.: "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)

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

[Publications] 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).

[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)