1995 Fiscal Year Annual Research Report

サイトカインによるシグナル伝達機構の解析

Research Project

Project/Area Number	07409001
Research Category	Grant-in-Aid for General Scientific Research (A)
Research Institution	The University of Tokyo
Principal Investigator	宮島篤東京大学, 分子細胞生物学研究所, 教授 (50135232)
Co-Investigator(Kenkyū-buntansha)	若尾宏東京大学, 分子細胞生物学研究所, 助手原孝彦東京大学, 分子細胞生物学研究所, 助手
Keywords	サイトカイン / サイトカイン受容体 / シグナル伝達 / 細胞増殖 / アポトーシス / 造血
Research Abstract	サイトカインによるシグナル伝達経路の解析を行うため、IL-3,Epoなどにより誘導される初期遺伝子を我々が開発したcDNAライブラリーサブトラクション法により検索した結果、c-myc,pim-1,Id-1など既存の遺伝子に加え、新たにSH-2ドメインをもつ分子を見いだし、CIS(cytokine inducible SH-2 protein)と名付けた。CISはチロシンリン酸化されたサイトカインレセプターに結合し、過剰発現させると細胞の増殖を抑制した。従って、CISはサイトカインのシグナルをフィードバック制御する因子である可能性が考えれるが、この分子の生理機能、作用機構についてはさらに検討を加える必要がある。また、これらのサイトカイン誘導遺伝子の中にオンコスタチンM(OSM)を見い出した。マウスOSMは遺伝子が単離されていなかったので、その生理機能の解析が進んでおらず、本研究でマウスOSMcDNAが得られたことで、遺伝子ターゲッテイング、トランスジェニックマウス作成などによる機能解析が可能となった。これはOSMの生理機能を探る上で極めて重要な意義を持つものである。さらに、造血細胞がIL-3やEpoなどの刺激によりオンコスタチンM-(OSM)を産生する現象を見い出したが、造血細胞からサイトカインによりOSMが産生されることの生理的な意味は不明であり、現在検討中である。造血細胞の細胞死の抑制にはRasの活性化が重要であることを見い出していたが、さらに細胞死抑制因子であるBcl-2,Bcl-Xの発現がRasの活性化で誘導されるという結果を得た。Rasの活性化がどのようにしてBcl-2の発現につながるのか、Rasによる細胞死抑制はBcl-2の発現だけで説明できるのかなどの点につき検討中である。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] Yoshimura,A: "A novel cytokine-inducible gene encodes an SH2-containing protein that binds to the tyrosine phosphorylated interleukin-3 and erythropoietin receptors" EMBO J.14. 2816-2826 (1995)
[Publications] Mui,A.L-F: "Interleukin-3,granulocyte-macrophage colony stimulating factor, and interleukin-5 transduce signals through two STAT5 homologues." EMBO J.14. 1166-1175 (1995)
[Publications] Nishinakamura,R: "Mice deficient for the IL-3/GM-CSF/IL-5 βc recepor exhibit lung pathology and impaired immune response,while βIL3 receptor-deficient mice are normal" Immunity. 2. 211-222 (1995)
[Publications] Hara,T: "Interleukin-3(IL-3)nonresponder inbred mouse strains carry the identical deletion of a branch point in the the IL-3 receptor α subunit gene." Blood. 85. 2331-2336 (1995)
[Publications] Wakao,H: "Interleukin-2 and erythropoietin activate STAT5 via distinct pathways." EMBO J.14. 2527-2535 (1995)
[Publications] Ho,A.S.Y: "Functional regions of the mouse interleukin 10 receptor cytoplasmic domain." Mol.Cell.Biol.15. 5043-5053 (1995)
[Publications] Mui,A.L-F: "Interleukin-3,granulocyte-macrophage colony stimulating factor,and interleukin 5 transduce signals through two forms of STAT5." J.Leukocyte Biology.57. 799-803 (1995)
[Publications] Kinoshita,T: "Suppression of apoptotic death in hematopoietic cells by signaling through the IL-3 and GM-CSF receptors." EMBO.J.14. 266-275 (1995)
[Publications] Ichihara,M: "mpaired interleukin 3(IL-3)response of the A/J mouse is caused by a branch point deletion in the IL-3 receptor α subunit gene" EMBO.J.14. 939-950 (1995)
[Publications] Miyajima,I: "The murine interleukin-3 receptor α subunit gene:chromosomal localization,genomic structure and promoter function." Blood.85. 1246-1253 (1995)
[Publications] Takagi,M: "Multi-colony stimulating activity of interleukin-5(IL-5)on hematopoietic progenitors from transgenic mouse that express IL-5 receptor α subunit consititutively" J.Exp.Med.181. 889-899 (1995)
[Publications] Kinoshita T: "Regulation of Bcl-2 expression by oncogenic Ras protein in hematopoietic cells" Oncogene. 10. 2207-2212 (1995)
[Publications] Copeland N.G: "Distribution of the memmalian Stat gene family in mouse chromosomes." Genomics. 29. 225-228 (1995)
[Publications] Hara,T: "Molecular cloning and functional characterization of a novel member of the C-C chemokine family" J.Immunol.155. 5352-5358 (1995)
[Publications] Damen,J.E: "Tyrosine 343 in the erythropoietin receptor positively regulates erythropoietin-induced cell proliferation and STAT5 activation." EMBO J.14. 5557-5568 (1995)
[Publications] Kitamura T: "Efficient screening of retroviral cDNA expression libraries" Proc.Natl.Acad.Sci.USA.92. 9146-9150 (1995)

1995 Fiscal Year Annual Research Report

サイトカインによるシグナル伝達機構の解析

Principal Investigator

宮島 篤 東京大学, 分子細胞生物学研究所, 教授 (50135232)

Research Products

[Publications] Yoshimura,A: "A novel cytokine-inducible gene encodes an SH2-containing protein that binds to the tyrosine phosphorylated interleukin-3 and erythropoietin receptors" EMBO J.14. 2816-2826 (1995)

[Publications] Mui,A.L-F: "Interleukin-3,granulocyte-macrophage colony stimulating factor, and interleukin-5 transduce signals through two STAT5 homologues." EMBO J.14. 1166-1175 (1995)

[Publications] Nishinakamura,R: "Mice deficient for the IL-3/GM-CSF/IL-5 βc recepor exhibit lung pathology and impaired immune response,while βIL3 receptor-deficient mice are normal" Immunity. 2. 211-222 (1995)

[Publications] Hara,T: "Interleukin-3(IL-3)nonresponder inbred mouse strains carry the identical deletion of a branch point in the the IL-3 receptor α subunit gene." Blood. 85. 2331-2336 (1995)

[Publications] Wakao,H: "Interleukin-2 and erythropoietin activate STAT5 via distinct pathways." EMBO J.14. 2527-2535 (1995)

[Publications] Ho,A.S.Y: "Functional regions of the mouse interleukin 10 receptor cytoplasmic domain." Mol.Cell.Biol.15. 5043-5053 (1995)

[Publications] Mui,A.L-F: "Interleukin-3,granulocyte-macrophage colony stimulating factor,and interleukin 5 transduce signals through two forms of STAT5." J.Leukocyte Biology.57. 799-803 (1995)

[Publications] Kinoshita,T: "Suppression of apoptotic death in hematopoietic cells by signaling through the IL-3 and GM-CSF receptors." EMBO.J.14. 266-275 (1995)

[Publications] Ichihara,M: "mpaired interleukin 3(IL-3)response of the A/J mouse is caused by a branch point deletion in the IL-3 receptor α subunit gene" EMBO.J.14. 939-950 (1995)

[Publications] Miyajima,I: "The murine interleukin-3 receptor α subunit gene:chromosomal localization,genomic structure and promoter function." Blood.85. 1246-1253 (1995)

[Publications] Takagi,M: "Multi-colony stimulating activity of interleukin-5(IL-5)on hematopoietic progenitors from transgenic mouse that express IL-5 receptor α subunit consititutively" J.Exp.Med.181. 889-899 (1995)

[Publications] Kinoshita T: "Regulation of Bcl-2 expression by oncogenic Ras protein in hematopoietic cells" Oncogene. 10. 2207-2212 (1995)

[Publications] Copeland N.G: "Distribution of the memmalian Stat gene family in mouse chromosomes." Genomics. 29. 225-228 (1995)

[Publications] Hara,T: "Molecular cloning and functional characterization of a novel member of the C-C chemokine family" J.Immunol.155. 5352-5358 (1995)

[Publications] Damen,J.E: "Tyrosine 343 in the erythropoietin receptor positively regulates erythropoietin-induced cell proliferation and STAT5 activation." EMBO J.14. 5557-5568 (1995)

[Publications] Kitamura T: "Efficient screening of retroviral cDNA expression libraries" Proc.Natl.Acad.Sci.USA.92. 9146-9150 (1995)

宮島篤東京大学, 分子細胞生物学研究所, 教授 (50135232)