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細胞増殖制御系におけるシグナル伝達機構

Research Project

Project/Area Number 61010027
Research Category

Grant-in-Aid for Cancer Research

Allocation TypeSingle-year Grants
Research InstitutionThe University of Tokyo

Principal Investigator

上代 淑人  東大, 医科学研究所, 教授 (90012690)

Co-Investigator(Kenkyū-buntansha) 山本 正幸  東京大学, 医科学研究所, 助教授 (40114706)
宇野 功  東京大学, 応用微生物研究所, 助教授 (60114401)
西川 克三  金沢医科大学, 教授 (10029960)
鈴木 紘一  東京都臨床医学総合研究所, 部長 (80011948)
宇井 理生  東京大学, 薬楽部, 教授 (50001037)
Project Period (FY) 1986
Project Status Completed (Fiscal Year 1986)
Budget Amount *help
¥16,300,000 (Direct Cost: ¥16,300,000)
Fiscal Year 1986: ¥16,300,000 (Direct Cost: ¥16,300,000)
Keywordsシグナル伝達機構 / Gタンパク質 / インスリン受容体 / カルシウムプロテアーゼ / Cキナーゼ / 百日咳毒素(IAP) / ras遺伝子 / 酵母アデニル酸シクラーゼ遺伝子
Research Abstract

細胞増殖のシグナルは、細胞増殖因子の細胞膜レセプターへの結合によって標的細胞に伝えられ、さらに増幅されて二次的メッセンジャーを介して細胞核に到達する。細胞増殖因子カスケードとよばれるこの一連の反応系を解明することを目的とする本研究は、今年度、申請書に記載した研究計画に従い、以下に述べるような研究成果を得た。1.ヒトインスリン受容体遺伝子に変異を導入し、インスリン作用発現には受容体のチロシンキナーゼ活性が必須であることを明らかにした。2.カルシウムプロテアーゼ(CANP)は、二次的メッセンジャーである【Ca^(2+)】やりん脂質の存在下に自己消化がおこり活性が発現することを見出した。3.活性型CANPの基質であり、シグナル伝達過程において中心的な役割を担っていると考えられるCキナーゼ(ウサギ)のCDNAクローニングを行なった。この結果、少なくともα,β,γ,δとよばれる4種のCキナーゼ分子が存在すること、さらにこれら4分子種の組織特異的発現が明らかにされた。4.リン脂質分解、Ca動員に引続いて細胞内に発生する遅いシグナル伝達に、IAP基質であるG蛋白質が関与していることが3T3細胞について示された。5.G蛋白質(ラットGs,Gi,Go)のαサブユニットのCDNAクローニングを行ないG蛋白質に共通なドメインと各G蛋白質に固有なドメインの存在を明らかにした。6.ras遺伝子に変異を導入し、GTP結結合能がトランスフォーム活性に必須であることを示した。7.分子遺伝学的解析が容易である酵母のシグナル伝達系については(1)分裂酵母におけるras相同遺伝子が接合フェロモンからのシグナル伝達系に関与していることが示された。(2)パン酵母のアデニル酸シクラーゼ遺伝子の欠失変異の解析から触媒中心ドメインおよびras遺伝子産物による制御に必須なドメインの一次構造上での配置を明らかにした。今後は、以上の成果を総合し、さらに発展させる計画である。

Report

(1 results)
  • 1986 Annual Research Report
  • Research Products

    (57 results)

All Other

All Publications (57 results)

  • [Publications] Nagata,S.;Tsuchiya,M.;Asano,S.;Kaziro,Y.;Yamazaki,T.;Yamamoto,O.;Hirata,Y.et al.: Nature. 319. 415-417 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Fukui,M.;Kozasa,T.;Kaziro,Y.;Takeda,T.;Yamamoto,T.: Cell. 44. 329-336 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Itoh,H.;Kozasa,T.;Nagata,S.;Nakamura,S.;Katada,T.;Kaziro,Y.et al.: Proc.Natl.Acad.Sci.USA. 83. 3776-3780 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Fukui,Y.;Kaziro,Y.;Yamamoto,M.: The EMBO J.5. 1991-1993 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Nagashima,K.;Kasai,M.;Nagata,S.;Kaziro,Y.: Gene. 45. 265-273 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Tsuchiya,M.;Asano,S.;Kaziro,Y.;Nagata,S.: Proc.Natl.Acad.Sci.USA. 83. 7633-7637 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Katada,T.: J.Biol.Chem.261. 5215-5221 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Kurose,H.: J.Biol.Chem.261. 6423-6428 (1986)

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      1986 Annual Research Report
  • [Publications] Katada,T.: J.Biol.Chem.261. 8182-8191 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Kikuchi,A.: J.Biol.Chem.261. 11558-11562 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Itoh,I.: Proc.Natl.Acad.Sci.USA. 83. 3776-3780 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Nogimori,K.: Biochemistry. 25. 1355-1363 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Hazeki,K.: Arch.Biochem.Biophys.246. 772-782 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Tsuda,M.: FEBS Lett.198. 5-10 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Oinuma,M.: FEBS Lett.207. 28-34 (1986)

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      1986 Annual Research Report
  • [Publications] Okada,F.: J.Neurochem.47. 454-459 (1986)

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      1986 Annual Research Report
  • [Publications] Emori,Y.: J.Biol.Chem.261. 9465-9471 (1986)

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      1986 Annual Research Report
  • [Publications] Emori,Y.: J.Biol.Chem.261. 9472-9476 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Kawasaki,H.: J.Biol.Chem.99. 1525-1532 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Imajoh,S.: J.Biochem.99. 1281-1284 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Imajoh,S.: J.Biochem.100. 633-642 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Aoki,K.: FEBS Lett.205. 313-317 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Ohno,S.: Nucl.Acid.Res.14. 5559 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] SuzuKi,K.: Biomed.Biochim.Acta. 110. 633-642 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Suzuki,K.: Int.J.Protein Chem.6. 7-15 (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] Miyake,S.: Nucl.Acid.Res.14. 8805-8817 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Ohno,S.: Nature. 325. 161-166 (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] Aoyama,T.: J.Kanazawa Med.Univ.11. 190-199 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] NishiKawa,K.: Methods in Enzymology. 146.

    • Related Report
      1986 Annual Research Report
  • [Publications] Matsumoto,K.: Yeast Cell Biol.101-111 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Uno,I.: Yeast Cell Biology. 113-123 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Matsumoto,K.: J.Bacteriol.

    • Related Report
      1986 Annual Research Report
  • [Publications] Shin,D.-Y.: Mol.Cell.Biol.

    • Related Report
      1986 Annual Research Report
  • [Publications] Ebina,Y.: Cell. 40. 747-758 (1985)

    • Related Report
      1986 Annual Research Report
  • [Publications] Ebina,Y.: Proc.Natl.Acad.Sci.USA. 82. 8014-8018 (1985)

    • Related Report
      1986 Annual Research Report
  • [Publications] Ebina,Y.: Proc.Natl.Acad.Sci.USA.

    • Related Report
      1986 Annual Research Report
  • [Publications] Nishida,Y.: Biochem.Biophys.Res.Commun.

    • Related Report
      1986 Annual Research Report
  • [Publications] Tominaga,S.: J.Biol.Chem.260. 1975-1978 (1985)

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      1986 Annual Research Report
  • [Publications] Tominaga.S.: J.Biol.Chem.260. 16406-16410 (1985)

    • Related Report
      1986 Annual Research Report
  • [Publications] Tominaga,S.: FEBS Lett.144. 112-116 (1982)

    • Related Report
      1986 Annual Research Report
  • [Publications] Tominaga,S.: J.Biochem.93. 1085-1092 (1983)

    • Related Report
      1986 Annual Research Report
  • [Publications] Tominaga,S.: J.Biochem.93. 1093-1100 (1983)

    • Related Report
      1986 Annual Research Report
  • [Publications] Fukui,Y.: Cell. 44. 329-336 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Sakai,K.: Agric.Biol.Chem.50. 1177-1182 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Yamamoto,M.: Microbiol.3. 234-237 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Fukui,Y.: The EMBO J.5. 1991-1993 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Shimoda,C.: J.Bacteriol.(1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] Abdel-Ghany,M.: Bioscience Report. 3. 275-282 (1983)

    • Related Report
      1986 Annual Research Report
  • [Publications] NaKamura,S.: Biochemistry. 23. 385-389 (1984)

    • Related Report
      1986 Annual Research Report
  • [Publications] Itoh,H.: Proc.Natl.Acad.Sci.USA. 83. 3776-3780 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Nakamura,S.: Arch.Biochem.Biophys.(1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] Hattori,S.: Mol.Cell.Biol.5. 1449-1455 (1985)

    • Related Report
      1986 Annual Research Report
  • [Publications] Beckner,S.K.: Nature. 317. 71-72 (1985)

    • Related Report
      1986 Annual Research Report
  • [Publications] Clanton,D.J.: Proc.Natl.Acad.Sci.USA. 83. 5076-5080 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Hattori,S.: J.Biol.Chem.261. 14582-14586 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Engel,D.: "The Interferon System" 73 (1985)

    • Related Report
      1986 Annual Research Report
  • [Publications] Tominaga,S.: "Biological Functions of Microtubules and Related Structures." Academic Press Japan, 11-22 (1982)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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