2002 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 / STAT5 / IL6 / NFKB
Research Abstract	レトロウイルスによる発現クローニング法に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. Mol 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た。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pim-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NFκB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

(13 results)

All Other

All Publications (13 results)

[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. 21. 844-848 (2002)
[Publications] Nosaka, T.: "Pim-1 expression is sufficient to induce cytokine independence in murin hematopoietic cells but is dispensable for BCB-ABL-medical transformation"Exp. Hematol.. 30. 697-702 (2002)
[Publications] Perez, O.D.: "Acitivation of the PKB/AKT pathway by ICAM-2"Immunity. 16. 51-65 (2002)
[Publications] Nagai, Y.: "Essential role of MD-2 in LPS responsiveness and TLR4 distribution"Nat. Immunol.. 3. 667-672 (2002)
[Publications] Gugasyan, R.: "Dok-related protein negatively regulates T cell development ts RasGTPase-activating protein and Nck docking sites"J. Cell Biol.. 158. 115-125 (2002)
[Publications] Stoeclin, G.: "Functional cloning of BRF-1, a regulator of ARE-dependent mRNA turnover"EMBO J.. 21. 4709-4718 (2002)
[Publications] Komano, H.: "A new functional screening system for identification of DNA encoding a regulator of γ-cleavage"J. Biol. Chem.. 277. 39627-39633 (2002)
[Publications] Ezoe, S.: "GATA-2 affects cytokine-dependent growth of hematopoietic cells through accumulation of p21^<WAF1> and p27^<Kip1> proteins"Blood. 100. 3512-3520 (2002)
[Publications] Yujiri, T.: "MEK kinase 1 interacts with focal adhesion kinase and regulates insulin receptor substrate-1 expression"J. Biol. Chem.. (in press). (2003)
[Publications] Minoshima, Y.: "Aurora B Phosphorylates MgcRacGAP and Induces RhoGAP Activity during M Phase : Identification of a RhoGAP Indispensable for Cytokinesis"Developmental Cell. (in press). (2003)
[Publications] Nosaka, T.: "Dwarfism and lymphoid deficiency in mice lacking twisted gastrulaiion"Mol. Cell. Biol.. (in press). (2003)
[Publications] Kitamura, T.: "Retrovirus-mediated gene transfer and expression cloning, powerful tools in functional genomics"Exp. Hematol.. (in press). (2003)

2002 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] 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. 21. 844-848 (2002)

[Publications] Nosaka, T.: "Pim-1 expression is sufficient to induce cytokine independence in murin hematopoietic cells but is dispensable for BCB-ABL-medical transformation"Exp. Hematol.. 30. 697-702 (2002)

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

[Publications] Nagai, Y.: "Essential role of MD-2 in LPS responsiveness and TLR4 distribution"Nat. Immunol.. 3. 667-672 (2002)

[Publications] Gugasyan, R.: "Dok-related protein negatively regulates T cell development ts RasGTPase-activating protein and Nck docking sites"J. Cell Biol.. 158. 115-125 (2002)

[Publications] Stoeclin, G.: "Functional cloning of BRF-1, a regulator of ARE-dependent mRNA turnover"EMBO J.. 21. 4709-4718 (2002)

[Publications] Komano, H.: "A new functional screening system for identification of DNA encoding a regulator of γ-cleavage"J. Biol. Chem.. 277. 39627-39633 (2002)

[Publications] Ezoe, S.: "GATA-2 affects cytokine-dependent growth of hematopoietic cells through accumulation of p21^<WAF1> and p27^<Kip1> proteins"Blood. 100. 3512-3520 (2002)

[Publications] Yujiri, T.: "MEK kinase 1 interacts with focal adhesion kinase and regulates insulin receptor substrate-1 expression"J. Biol. Chem.. (in press). (2003)

[Publications] Minoshima, Y.: "Aurora B Phosphorylates MgcRacGAP and Induces RhoGAP Activity during M Phase : Identification of a RhoGAP Indispensable for Cytokinesis"Developmental Cell. (in press). (2003)

[Publications] Nosaka, T.: "Dwarfism and lymphoid deficiency in mice lacking twisted gastrulaiion"Mol. Cell. Biol.. (in press). (2003)

[Publications] Kitamura, T.: "Retrovirus-mediated gene transfer and expression cloning, powerful tools in functional genomics"Exp. Hematol.. (in press). (2003)

北村俊雄東京大学, 医科学研究所, 教授 (20282527)