2002 Fiscal Year Annual Research Report

冠動脈および大動脈の血管内皮に発現する新規接着分子の解析

Research Project

Project/Area Number	14657240
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	TGFβ / 大動脈 / 血管平滑筋 / 心臓 / 膜蛋白質 / レセプター / シグナル
Research Abstract	我々のグループが開発した効率のよいシグナルシークエンスタラップ法SST-REX法を利用して心臓で発現する膜蛋白質・分泌蛋白質をスクリーニングした。約300同定しえた膜蛋白質・分泌蛋白質のうち11種の未知の分子に関して分子構造や発現を解析した。これらの11種の未知の分子のうちI型膜蛋白質バゾリンを解析した。In situハイブリダイゼーションによってバゾリンは大動脈の平滑筋層に特異的に発現していることが判明した。またその発現は胎生期にも強く認められ、細胞の脱分化でその発現が抑制されることからバゾリンの発現はdevelopmentalに制御を受けていることが示唆された。興味深いことにバゾリンはTGFβと約1nMの親和性で結合することが判明した。さらに詳細な解析を行うことにより、バゾリンはTGFβのTGFβレセプターへの結合を競合的に阻害することによってTGFβシグナルを負に調節することが明らかとなった。今後バゾリンが血管障害モデルにおいてTGFβのシグナルを抑制することができるかなどを調べていく予定である。

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 BCR-ABI-mediated 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 the 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 gastrulation"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

冠動脈および大動脈の血管内皮に発現する新規接着分子の解析

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 BCR-ABI-mediated 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 the 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 gastrulation"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)