2001 Fiscal Year Annual Research Report

MgcRacGAP/Cyk4によるサイトキネシス制御と細胞分化・増殖

Research Project

Project/Area Number	13043010
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	シグナル伝達 / 遺伝子 / サイトキネシス / 細胞周期 / 分化
Research Abstract	我々が造血細胞の分化関連遺伝子として同定したマウスMgcRacGAPは間期の細胞では核内に存在し、細胞分裂期に分裂スピンドルの微小管に添ってmid body(中央体)に移動することが明らかになった。また、そのN末に存在するミオシン様ドメインを欠失し微小管に結合できない変異体やGAP活性陰性の変異体を細胞に強制発現するとサイキネシスがうまくいかなくなり、多核細胞が著明に増加することも判明した(Hirose et al.J.Biol.Chem.,2001)。これらの結果は、MgcRacGAPがサイトキネシスの完了に重要な役割を果たす分子であることを示している。最近、我々は中央体に移動したMgcRacGAPのみセリン残基にリン酸化を受けること見いだした。我々はこの実験結果に基づき、MgcRacGAPのセリンリン酸化がGAP活性の変化を誘導することがサイトキネシスの完了への引き金となっているという仮説をたて、リン酸化酵素の同定とリン酸化によるMgcRacGAPのGAP活性の変化を調べる予定で実験を行っている。リン酸化酵素の候補としてMgcRacGAPと同様の局在を示すCitronキナーゼ、AIM-1、Rhoキナ-ゼ、Polo様キナーゼの4つのリン酸化酵素を精製し、MgcRacGAPをリン酸化する活性を有するかどうか検討している。またリン酸化酵素を同定したあとは、リン酸化部位を同定し、MgcRacGAPのリン酸化によって何が惹起されるのかを調べていく予定である。

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"Cytogenetics 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 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+-ATPAse-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

MgcRacGAP/Cyk4によるサイトキネシス制御と細胞分化・増殖

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] 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 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+-ATPAse-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)