2002 Fiscal Year Annual Research Report

Th2細胞優位に発現されるサイトカインレセプターδ1の解析

Research Project

Project/Area Number	13037011
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	Th1 / Th2 / 生物・生体工学 / 遺伝子 / シグナル伝達 / ウイルス
Research Abstract	我々は自ら開発したシグナルシークエンストラップ法SST-REX(Kojima and Kitamura, Nat Biotech, 1999)を利用してTh2細胞優位に発現しているマウス新規サイトカインレセプターδ1を同定した(Fujio et al. Blood, 2001)。その後δ1がTSLP(Thymic Stroma Lymph opoietein)というサイトカインのレセプターのサブユニットであることが判明した。δ1がIL7レセプターとヘテロダイマーを形成し機能性TSLPレセプターを形成する。δ1がIL2/IL4/IL7/IL9/IL15レセプターの共通のサブユニットである共通γ鎖と相同性を有することから、他のサイトカインのレセプターにも関与している可能性を考え検索を行っているが現在までにこの可能性を示唆するデータは得られていない。米国NIHグループとの共同研究でδ1/TSLPレセプターのノックアウトマウスを作製したが現在までのところ胸腺がやや小さい以外は目立った表現型は見つかっていない。ヒトでもδ1/TSLPレセプターと構造上の類似性を有するサイトカインレセプターのcDNAを単離したが、遺伝子座はXYの偽常染色体上のGM-CSFレセプターおよびIL-3レセプターαサブユニットの近傍に存在することが判明した(Tonozuka et al. Cytogenet and Cell Genet, 2001)。今後、最近作製したマウスδ1に対するモノクローナル抗体を利用して種々の細胞における発現を調べる予定である。

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 murine hematopoietic cells, but is dispensable for BCR-ABL-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 its 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

Th2細胞優位に発現されるサイトカインレセプターδ1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 murine hematopoietic cells, but is dispensable for BCR-ABL-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 its 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)