1991 Fiscal Year Annual Research Report

活性化T細胞におけるシグナル伝達とILー3とGMーCSF遺伝子の発現機構の解析

Research Project

Project/Area Number	03454544
Research Institution	The University of Tokyo
Principal Investigator	横田崇東京大学, 医科学研究所, 助教授 (50134622)
Co-Investigator(Kenkyū-buntansha)	村松正明東京大学, 医科学研究所, 教務職員 (50230008) 新井賢一東京大学, 医科学研究所, 教授 (00012782)
Keywords	インタ-ロイキン3 / コロニ-刺激因子 / シグナル伝達 / DNA結合タンパク質 / 転写因子 / エンハンサ-配列 / トランスアクチベ-タ- / シス調節領域
Research Abstract	GMーCSF遺伝子においてはCLE2/GC boxがT細胞活性化シグナルに必要なエンハンサ-配列として同定されていたが、さらにCLE2/GC boxとTATA box間に存在するCLEO配列が両者を連結するブリッジ配列として構成的に必要であることが明らかとなった。さらにGMーCSF遺伝子のcis調節領域[誘導的エンハンサ-(CLE2/GC box),Bridge(CLE0)]とILー3遺伝子で同定されたcis調節領域[CTエレメント=GC rich region]の両者が機能的に同一であるかどうかを検討した。その結果CLE0とCTエレメントは機能的に同一ではないことが明らかとなった。さらにILー3遺伝子を活性化するGMーCSF遺伝子の誘導的エンハンサ-としてCLE1,CLE2/GC box,CLE0までの領域が必要であることが示唆された。さらにT細胞活性化シグナルあるいはp40taxやBPV E2等のウイルスタンパク質等に反応してGMーCSF遺伝子のcis調節領域に誘導的(NFーGM2)あるいは構成的(A1,A2,B)に結合するDNA結合タンパク質を同定し、NFーGM2とNFーкBあるいはrel遺伝子との関連、A1とSp1との関連を示した。現在同時に活性化T細胞から調製した試験管内転写系を用いてGMーCSF,ILー3プロモ-タ-の調節領域の同定とそれに結合するタンパク質のcDNAクロ-ンをSouthwestern法を用いて単離しその解析を行っている。また。p40tax等のウイルス産物がシグナル伝達系と相互作用することにより直接的にリンホカイン遺伝子を活性化する可能性を示唆した。

Research Products

(19 results)

All Other

All Publications (19 results)

[Publications] Mauxion,F.et.al.: "Comparison of constitutive and inducible transcriptional enhancement mediated by KBー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)
[Publications] Miyatake,S.et.al.: "Characterization of the mouse GMーCSF promoter:nuclear factors that interact with an element shared by three lymphokine genes:GMーCSF,ILー4,and ILー5" Molecular and Cellular Biology. 11. 5894-5909 (1991)
[Publications] Kitamura,T.et.al.: "Expression cloning of human ILー3 receptor cDNA and reconstitution of high affinity receptors for human ILー3 and GMーCSF" Cell. 66. 1165-1174 (1991)
[Publications] Tsuboi,A.et.al.: "A nuclear factor NFGM2,essential for induction of GMーCSF gene in response to Tーcell activation:purification from T cell leukemia line Jurkat cell and relationship to NFーkB" International Immunology. 3. 807-817 (1991)
[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)
[Publications] Arai,K.et.al.: "Cytokine network and regulation of inflammatory response" Excepta Medica. (1991)
[Publications] Nishida,J.et.al.: "Definition of GC rich motif as regulatoy sequence of thehuman ILー3 gene:coordinate regulation of the ILー3 gene by CLE2/GC box of the GMーCSF gene in T cell activation" International Immunology. 3. 245-254 (1991)
[Publications] Watanabe,S.et.al.: "Colony stimulating factors and cytokine receptor network" Current Opinion in Biotechnology. 2. 227-237 (1991)
[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)
[Publications] Schreurs,J.et.al.: "AIC2A is a component of the purified high affinity mouse ILー3 receptor:temperatureーdependent modulation of AIC2A structure" International Immunology. 3. 1231-1242 (1991)
[Publications] Ozu,M.et.al.: "Regulation of the ILー3 gene and structure and function of the ILー3 receptor" Advance in Neuroimmunology. 2. 32-52 (1992)
[Publications] Wang,H.M.et.al.: "Structure of mouse ILー3 binding protein(AIC2A):Amino acid residues critical for ILー3 binding" Journal of Biological Chemistry. (1992)
[Publications] Garret,K.P.et.al.: "The Cーterminus of rat RAP30 is similar in sequence to region 4 of bacterial sigma factors and is required for function" submitted. (1992)
[Publications] Hisatsune,T.et.al.: "A suppressive lymphokine derived from Ts clone 13G2 is ILー10" Lymphokine Research. (1992)
[Publications] Miyajima A.et.al.: "Cytokine receptors and signal transduction" Annual Review of Immunology. 10. 295-331 (1992)
[Publications] Abe,E.et.al.: "Elevenーbase pair DNA sequence motif unique to human ILー4 gene confers responsiveness to T cell activation signals" Proceedings of National Academy of Science USA. (1992)
[Publications] Hatake,K.et.al.: "Human Cytokines" Blackwell Scientific Publications Inc.(Aggarwal,B.B.and Gutterman,J.U.,eds), 135-142(8) (1991)
[Publications] Miyatake,S.et.al.: "Molecular Biology of Lymphokines" VCH Publishers,Inc., 35-37(3) (1991)
[Publications] Yokota,T.et.al.: "Cytokines and Infectious Disease" Marcel Decker Inc.(Bermudes,L.Z.and Steems,P.,eds), (1992)

1991 Fiscal Year Annual Research Report

活性化T細胞におけるシグナル伝達とILー3とGMーCSF遺伝子の発現機構の解析

Principal Investigator

横田 崇 東京大学, 医科学研究所, 助教授 (50134622)

Research Products

[Publications] Mauxion,F.et.al.: "Comparison of constitutive and inducible transcriptional enhancement mediated by KBー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)

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

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

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

[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)

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

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

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

[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)

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

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

[Publications] Wang,H.M.et.al.: "Structure of mouse ILー3 binding protein(AIC2A):Amino acid residues critical for ILー3 binding" Journal of Biological Chemistry. (1992)

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

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

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

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

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

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

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

横田崇東京大学, 医科学研究所, 助教授 (50134622)