• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

造血因子の構造と作用の分子生物学的検討と生体内作用

Research Project

Project/Area Number 03252101
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionThe University of Tokyo

Principal Investigator

新井 賢一  東京大学, 医科学研究所, 教授 (00012782)

Co-Investigator(Kenkyū-buntansha) 高津 聖志  東京大学, 医科学研究所, 教授 (10107055)
長田 重一  (財)大阪バイオサイエンス研究所, 部長 (70114428)
平野 俊夫  大阪大学, 医学部, 教授 (40136718)
間野 博行  東京大学, 医学部, 助手
Project Period (FY) 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥40,000,000 (Direct Cost: ¥40,000,000)
Fiscal Year 1991: ¥40,000,000 (Direct Cost: ¥40,000,000)
Keywords造血因子 / インタ-ロイキン / コロニ-刺激因子 / レセプタ- / 情報伝達 / サイトカイン / 発現クロ-ニング / 分子生物学
Research Abstract

1.新井らはこれまでILー3及びGMーCSFレセプタ-の解析と遺伝子の単離を行なってきた。その結果高親和性レセプタ-は低親和性結合能を持つα鎖と単独では結合能を持たないβ鎖の二つのサブユニットからなっており、さらにβ鎖を両者が共有することがそれぞれのサブユニットcDNAをクロ-ニングし高親和性レセプタ-を発現再構成することにより明らかとなった。シグナル伝達にはβ鎖が関与し、さらにαβに相互作用するチロシンキナ-ゼの存在が示唆された。ILー3,GMーCSF,ILー4遺伝子の調節領域と結合するタンパク質を同定しその解析を行なった。2.間野らはこれまでエリスロポエチン、GMーCSFのレセプタ-について、その生化学的特徴を明らかにした。さらに2種類のGMーCSFレセプタ-についてその精製、cDNAクロ-ニングを進めている。3.平野らはILー6の純化、cDNAクロ-ニングを行ない、その広範な生理作用の詳細な解析を行なってきた。さらにILー6レセプタ-と会合分子のcDNAクロ-ニングを行ない会合分子がシグナル伝達に関与する分子であることを明らかにした。4.長田らはGーCSFレセプタ-cDNAに種々の変異を導入しシグナル伝達に必須な領域を同定した。GーCSFおよびそのレセプタ-の染色体遺伝子の単離、構造解析を行なった。5.岡山らは真核細胞を宿主としたcDNA発現クロ-ニングシステムを完成しこのシステムを用いて3種のヒトの細胞周期G2期制御遺伝子を単離した。これらがタンパク質燐酸化酵素とその抑制遺伝子であることが明らかとなった。6.元吉らはヒト尿中にMーCSF(CSFー1)を発見し純化、cDNAクロ-ニングに成功した。ヒトhMーCSFの血中コレステロ-ル低下作用を発見した。7.高津らは低親和性ILー5レセプタ-α鎖cDNAをパニング法を用いてクロ-ニングした。高親和性ILー5レセプタ-をα鎖とβ鎖(AIC2B)を用いて再構成し、β鎖(AIC2B)が高親和性GMーCSF及びILー3レセプタ-の共通のコンポネントでもあることを示した。

Report

(1 results)
  • 1991 Annual Research Report
  • Research Products

    (62 results)

All Other

All Publications (62 results)

  • [Publications] Mauxion,F.et.al.: "Comparison of constitutive and inducible transcriptional enhancement mediated by KB-related sequences:modulation of activity in B cells by human T cell leukemia virus type I tax gene" Proceedings of National Academy of Science USA. 88. 2141-2145 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Miyatake,S.et.al.: "Characterization of the mouse GM-CSF promoter:nuclear factors that interact with an element shared by three lymphokine genes:GM-CSF,IL-4,and IL-5" Molecular and Cellular Biology. 11. 5894-5909 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kitamura,T.et.al.: "Expression cloning of human IL-3 receptor cDNA and reconstitution of high affinity receptors for human IL-3 and GM-CSF" Cell. 66. 1165-1174 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tsuboi,A.et.al.: "A nuclear factor NFGM2,essential for induction of GM-CSF gene in response to T-cell activation:purification from T cell leukemia line Jurkat cell and relationship to NF-kB" International Immunology. 3. 807-817 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nomura,N.et.al.: "Identification of eleven single strand initiation sequences(ssi) for priming of DNA replication in the F,R6K,R100 and ColE2 plasmids" Gene. 108. 15-22 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Arai,K.et.al.: "Cytokine network and regulation of inflammatory response" Excepta Medica. (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nishida,J.et.al.: "Definition of GC rich motif as regulatoy sequence of thehuman IL-3 gene:coordinate regulation of the IL-3 gene by CLE2/GC box of the GM-CSF gene in T cell activation" International Immunology. 3. 245-254 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Watanabe,S.et.al.: "Colony stimulating factors and cytokine receptor network" Current Opinion in Biotechnology. 2. 227-237 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kitamura,T.et.al.: "Reconstitution of functional receptors for human granulocytemacrophage colony stimulating factor:requirement of the b subunit for signaling" Proceedings of National Academy of Science USA. 88. 5082-5086 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Schreurs,J.et.al.: "AIC2A is a component of the purified high affinity mouse IL-3 receptor:temperature-dependent modulation of AIC2A structure" International Immunology. 3. 1231-1242 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ozu,M.et.al.: "Regulation of the IL-3 gene and structure and function of the IL-3 receptor" Advance in Neuroimmunology. 2. 32-52 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Wang,H.M.et.al.: "Structure of mouse IL-3 binding protein (AIC2A):Amino acid residues critical for IL-3 binding" Journal of Biological Chemistry. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Garret,K.P.et.al.: "The C-terminus of rat RAP30 is similar in sequence to region 4 of bacterial sigma factors and is required for function" submitted. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hisatsune,T.et.al.: "A suppressive lymphokine derived from Ts clone 13G2 is IL-10" Lymphokine Research. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Miyajima A.et.al.: "Cytokine receptors and signal transduction" Annual Review of Immunology. 10. 295-331 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Abe,E.et.al.: "Eleven-base pair DNA sequence motif unique to human IL-4 gene confers responsiveness to T cell activation signals" Proceedings of National Academy of Science USA. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ishihara,T.et.al.: "Molecular cloning and expression of a cDNA encoding the secretin receptor" EMBO J.10. 1635-1641 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Itoh,N.et al.: "The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis" Cell. 66. 233-243 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Chiba,S.et al: "Establishment and erythroid differentiation of a cytokinedependent humanleukemic cell line F-36:A parental line requiring granulocyte-macrophage colony-stimulating factor or interleukin-3,and a subline requiring erythropoietin" Blood. 78. 2261-2268 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Sasaki,K.et al.: "Identification of a solible GM-CSF binding protein in the supernatant of a human choriocarcinoma cell line" Biochem.Biophys.Res.Commun.

    • Related Report
      1991 Annual Research Report
  • [Publications] Taketazu,F.et al.: "IL-3 specifically inhibits GM-CSF binding to the higher affinity receptor" J.Cell.Physiol.146. 251-257 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tanaka,T.et al.: "Stimulatory effects of granulocyte colony-stimulating factor on CFU-S differentiation and pre-CSF-S proliferation in mice" Blood. 77. 2597-2602 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Sugiyama,H.et al.: "V-ABL does not abolish IL-6 requirement by murine plasmacytoma cells" Int.J.Cancer. 48. 234-238 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Fukunaga,M.et al.: "Signal transduction mechanism of interleukin 6 in cultured rat mesangial cells" FEBS Letter. 285. 265-267 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takenawa,J.et al.: "Enhanced expression of interleukin-6 in primary human renal cell carcinomas" J.Nat.Cancer Inst.83. 1668-1672 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hirano,T.: "Interleukin 6 (IL-6) and its receptor:Their role in plasma cell neoplasias" Int.J.Cell Cloning. 9. 166-184 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Oritani,K.et al.: "Retinoic acids inhibits IL-6-induced macrophage differentiation and apoptosis in a murine hematopoietic cell line,Y6" manuscript in preparation.

    • Related Report
      1991 Annual Research Report
  • [Publications] Nakajima,K.et al.: "Involvement of ETS and CREB/ATF families in the IL-6 signal transduction pathway resulting in the junB gene activation" manuscript in preparation.

    • Related Report
      1991 Annual Research Report
  • [Publications] Lee,M.Y.et al.: "Bone modulation in sustained hemopoietic stimulation in mice" Blood. 70. 2135-2141 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kinashi,T.et al.: "Premature expression of the macrophage colony-stimulating factor receptor on a multipotential stem cell line does not alter differentiation lineages controlled by stromal cells used for coculture" J.Exp.Med.173. 1267-1279 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Fukunaga,R.et al.: "Functional domains of the granulocyte colony-stimulating factor receptor" EMBO J.10. 2855-2865 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Asano,M.et al.: "Three individual regulatory elements of the promoter positively activates the transcription of the gene for granulocyte colony-stimulating factor" Gene. 107. 241-246 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shimano,H.et al.: "Plasma cholesterol-lowering activity of monocyte colony-stimulating factor (M-CSF)" Ann NY Acad Sci. 587. 362-370 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Masaoka,T.et al.: "Double-blind test of human urinary macrophage colony-stimulating factor for allogeneic and syngeneic bone marrow transplantation" Br J.Haematol.76. 501-505 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Suzu,S.et al.: "Characterization of macrophage colony-stimulating factor in body fluids by immunoblot analysis" Blood. 77. 2160-2165 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Saito,S.et al.: "Enhancing effects of human macrophage colony-stimulating factor on the secretion of human chorionic gonadotropin by human chorionic villous cells and tPA30-1 cells" Biochem.Biophys.Res.Commun.178. 1099-1104 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kayashima,S.et al.: "Effects of macrophage colony-stimulating factor on reduction of viable bacteria and survival of mice during Listeria monocytogenesis infection:Charactristics of monocyte subpopulations" Infection and Immunity. 59. 4677-4680 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ohsaka,A.et al.: "Enhanced neutrophil functions in a patient with colony stimulating factor-producing lung cancer" J.Int.Med.230. 459-462 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Konenaga,M.et al.: "The role of interleukin-5 (IL-5) in protective immunity to Strongyloides venezuelensis infection in mice" Immunology. 72. 502-507 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yamaguchi,N.et al.: "Murine interleukin 5 receptor isolated by immunoaffinity chromatography:comparison of determined N-terminal sequence and deduced primary sequence from cDNA and implication of a role of the intracytoplasmic domain" Int.Immunol.3. 889-898 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Murata,Y.et al.: "Molecular cloning and characterization of the human interleukin 5 receptor" J.Exp.Med.

    • Related Report
      1991 Annual Research Report
  • [Publications] Sonoda,E.et al.: "Differential regulation of IgA production by TGFB and IL-5:TGFB induces class switch of surface IgA B cells,whereas IL-5 promotes postswitch maturation into IgA-secreting cells" Cell.Immunol.

    • Related Report
      1991 Annual Research Report
  • [Publications] Migita,M.et al.: "Characterization of the human interleukin 5(IL-5) receptors on eosinophils" Cell.Immunol.133. 484-497 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hitoshi,Y.et al.: "In vivo administration of antibody to murine IL-5 receptor inhibits eosinophilia of IL-5 transgenic mice" Int.Immunol.3. 135-139 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tominaga,A.et al.: "Transgenic mice expressing a B cell growth and differntiation factor (interleukin 5) gene develop eosinophilia and autoantibody production" J.Exp.Med.173. 429-438 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Mita,S.et al.: "Molecular characterization of the B chain of the murine interleukin 5 (IL-5) receptor" Int.Immunol.3. 665-672 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takaki,S.et al.: "Identification of the second subunit of the murine interleukin 5 receptor:Interleukin-3 receptor-like protein,AIC2B is the component of the high affinity interleukin-5 recptor" EMBO J.10. 2833-2838 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takatsu,K.: "Interleukin 5 and its receptor" Microbiol.Immunol.35. 593-606 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takamizawa,A.et al.: "Structure and organization of the hepatitis C virus genome isolated from human carriers" J.Virology. 65. 1105-1113 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nagata,A.et al.: "An additional homolog of the fission yeast cdc25+ gene exists in human and is over-expressed in some cancer cells" New Biologist. 3. 959-968 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Igarashi,M.et al.: "Weel+-like gene in human cells" Nature. 353. 80-83 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Eiden,M.V.et al.: "Suppression of the chemically transformed phenotype of BHK cells by a human cDNA" Mol.Cell.Biol.11. 5321-5329 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Okazaki,N.et al.: "The ste4+ gene,essential for sexual differentiation of Schizsaccharomyces pombe,encodes a protein with a leucine zipper motif" Nucleic Acids Res.19. 7043-7047 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Masuda,A.et al.: "Signal transduction cascade shared by epidermal growth factor and platelet-derived growth factor is major pathway for oncogenic transformation in NRK cells" New Biologist.

    • Related Report
      1991 Annual Research Report
  • [Publications] Hatake,K.et.al.: "Human Cytokines" Blackwell Scientific Publications Inc.(Aggarwal,B.B.and Gutterman,J.U.,eds), 135-142(8) (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Miyatake,S.et.al.: "Molecular Biology of Lymphokines" VCH Publishers,Inc., 35-37(3) (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yokota,T.et.al.: "Cytokines and Infectious Disease" Marcel Decker Inc.(Bermudes,L.Z.and Steems,P.,eds), (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Motoyoshi,K.: "Frontiers of Mucosal Immunology" Elsevier Science Publishers, 903 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hanazono,Y.et al.: "Myelodysplastic syndrome and cytokines" Elsevier Science Publishers B.V., 3-12(10) (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hirano,T.,and Kishimoto,T.(Talal,N.ed): "Autoimmunity:Molecular,Virology,Genetics,Immunologic and Clinical Aspects" Academic Press, 17 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hirano,T.: "The Cytokine Handbook" Academic Press(Thompson,A.ed), 22 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Motoyoshi,K.: "Hematopoietic Growth Factors in Clinical Applications" Marcel Dekker Inc., 469 (1991)

    • Related Report
      1991 Annual Research Report

URL: 

Published: 1991-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi