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Molecular Mining and Functional Analysis of Cell Growth Control System

Research Project

Project/Area Number 15570116
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionKobe University

Principal Investigator

YOSHINO Ken-ichi  Kobe University, Biosignal Research Center, Assistant Professor, バイオシグナル研究センター, 助手 (90280792)

Co-Investigator(Kenkyū-buntansha) YONEZAWA Kazuyoshi  Kobe University, Biosignal Research Center, Professor, バイオシグナル研究センター, 教授 (70283900)
TOKUNAGA Chiharu  Kobe University, Biosignal Research Center, Assistant Professor, バイオシグナル研究センター, 助手 (70335462)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsmTOR / rapter / cell growth / mass spectrometry / amino acid / tuberous sclerosis / pyrimidine biosynthesi / heat shock protein 90
Research Abstract

The mammalian target of rapamycin (mTOR) controls cell growth (increase in cell mass or size) in response to availability of nutrient such as amino acids. The mTOR has been known to function as an integrator of larger signaling pathways for cell growth, however, little has been known about members of mTOR signaling.
We found the mammalian homolog protein of LST8, which was registered as Similar to G beta-like protein "Gable" in mammalian, is one of components mTOR complex. The mLST8 is a highly conserved 36 kDa protein that consists almost entirely seven WD40 repeats with high sequence similarity to those found in the beta subunit of heterotorimeric G proteins.
We identified an enzyme which takes part in pyrimidine biosynthesis as an interacting protein of mLST8 or WD40 domain of raptor. The pyrimidine ring is derived from Gln and Asp, and bicarbonate. This finding suggests that mTOR controls pyrimidine biosynthesis as well as protein synthesis,
The TSC1-TSC2 heterodimer (tuberous sclerosis gene products complex) and the small GTPase Rheb (Ras-homolog enriched in brain) have been known as upstream regulator of mTOR. The TSC2 acts as a GTPase activating protein against Rheb. We found another novel GTPase activating protein which interacts to TSC1,as well as TSC2. The molecular size of the novel GTPase activating protein was found to be 32 kDa, and it was shown that the protein interacts to the C-terminal coiled-coil (881-996) of TSC1.
We showed that the heat shock protein 90 (Hsp90) was co-purified with raptor. Geldanamycin, a potent inhibitor of Hsp90, disrupted the in vivo binding of Hsp90 to raptor without affecting the association of raptor and mTOR, and suppressed the phosphorylation by mTOR of the downstream translational regulators. It is suggested that the mTOR signaling pathway is a novel target of geldanamycin.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (62 results)

All 2004 2003 Other

All Journal Article (49 results) Book (3 results) Publications (10 results)

  • [Journal Article] Raptor,a binding partoner of target of rapamycin.2004

    • Author(s)
      Yonezawa, K.
    • Journal Title

      Biochem.Biophys.Res.Commun. 313・2

      Pages: 437-441

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] mTOR integrates amino acid-and energy-sensing pathways.2004

    • Author(s)
      Tokunaga, C.
    • Journal Title

      Biochem.Biophys.Res.Commun. 313・2

      Pages: 443-446

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dissociation of rapotor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR functon.2004

    • Author(s)
      Oshiro, N.
    • Journal Title

      Genes Cells 9・4

      Pages: 359-366

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells.2004

    • Author(s)
      Murakami, M.
    • Journal Title

      Mol.Cell Biol. 24・15

      Pages: 6710-6718

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Brain-derived neurotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synhesis in neuronal dendrites.2004

    • Author(s)
      Takei, N.
    • Journal Title

      J.neurosci. 24・44

      Pages: 9760-9769

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] mTOR signaling pathway.2004

    • Author(s)
      Yonezawa, K.
    • Journal Title

      Hepatol.Res. 30S

    • NAID

      10015455361

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ラパマイシン標的タンパク質mTORシグナル伝達系2004

    • Author(s)
      徳永 千春
    • Journal Title

      細胞工学 23・3

      Pages: 340-348

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] 細胞環境中のアミノ酸バランスを感知するmTORシグナル伝達機構2004

    • Author(s)
      中嶋 昭雄
    • Journal Title

      Bio Clinica 19・4

      Pages: 308-312

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 質量分析法と配列データベースを利用するタンパク質同定法2004

    • Author(s)
      吉野 健一
    • Journal Title

      J.Mass Spectrom.Soc.Jpn. 52・3

      Pages: 106-129

    • NAID

      10013283351

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] mTOR(mammalian Target of Rapamycin).2004

    • Author(s)
      米澤 一仁
    • Journal Title

      生体の科学 55・5

      Pages: 382-383

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 肝臓病の最近の話題「mTOR」について2004

    • Author(s)
      米澤 一仁
    • Journal Title

      Live 日常診療に診る肝臓病治療 6

      Pages: 11-11

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] mTOR integrates amino acid- and energy-sensing pathways.2004

    • Author(s)
      Chiharu, Tokunaga
    • Journal Title

      Biochem.Biophys.Res.Commun. 313-2

      Pages: 443-446

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Raptor, a binding partner of target of rapamycin.2004

    • Author(s)
      Kazuyoshi, Yonezawa
    • Journal Title

      Biochem.Biophys.Res.Commun. 313-2

      Pages: 437-441

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function.2004

    • Author(s)
      Noriko, Oshiro
    • Journal Title

      Genes Cells 9-4

      Pages: 359-366

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Kinase activities associated with mTOR.2004

    • Author(s)
      Kazuyoshi, Yonezawa
    • Journal Title

      TOR : Target of Rapamycin(Curr.Top.Microbiol.Immunol.)(Thomas, G., Sabatini, D.M., & Hall, M.N.(Eds.)) 279

      Pages: 271-282

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells.2004

    • Author(s)
      Mirei, Murakami
    • Journal Title

      Mol.Cell Biol. 24-15

      Pages: 6710-6718

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Brain-derived neurotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synthesis in neuronal dendrites.2004

    • Author(s)
      Nobuyuki, Takei
    • Journal Title

      J.Neurosci. 24-44

      Pages: 9760-9769

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] mTOR signaling pathway.2004

    • Author(s)
      Kazuyoshi, Yonezawa
    • Journal Title

      Hepatol.Res. 30S

    • NAID

      10015455361

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mammalian Target of Rapamycin (mTOR) Signaling System.2004

    • Author(s)
      Chiharu, Tokunaga
    • Journal Title

      Cell Technol. 23-3

      Pages: 340-348

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Sensing of extra-cellular amino acid balance by mTOR signaling system.2004

    • Author(s)
      Akio, Nakashima
    • Journal Title

      Bio Clinica 19-4

      Pages: 18-22

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mass spectrometry-based protein identification by correlation with sequence database.2004

    • Author(s)
      Ken-ichi, Yoshino
    • Journal Title

      J.Mass Spectrom.Soc.Jpn. 52-3

      Pages: 106-129

    • NAID

      10013283351

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] mTOR (mammalian Target of Rapamycin).2004

    • Author(s)
      Kazuyoshi, Yonezawa
    • Journal Title

      Seitai no Kagaku 55-5

      Pages: 382-383

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] mTOR (as a Current topic in Liver Disease Research)2004

    • Author(s)
      Kazuyoshi, Yonezawa
    • Journal Title

      Liv Nichijo Shinryo ni miru Kanzobyochiryo 6

      Pages: 11-11

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Raptor, a binding partner of target of rapamycin.2004

    • Author(s)
      Yonezawa, K.
    • Journal Title

      Biochem.Biophys.Res.Commun. 313・2

      Pages: 437-441

    • Related Report
      2004 Annual Research Report
  • [Journal Article] mTOR integrates amino acid- and energy-sensing pathways.2004

    • Author(s)
      Tokunaga, C.
    • Journal Title

      Biochem.Biophys.Res.Commun. 313・2

      Pages: 443-446

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function.2004

    • Author(s)
      Oshiro, N.
    • Journal Title

      Genes Cells 9・4

      Pages: 359-366

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Molecular identification and characterization of Xenopus egg uroplakin III, an egg raft-associated transmembrane protein that is tyrosine-phosphorylated upon fertilization.2004

    • Author(s)
      Sakakibara, K.
    • Journal Title

      J.Biol.Chem. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A possible linkage between AMP-activated protein kinase(AMPK) and mammalian target of rapamycin(mTOR) signalling pathway.2003

    • Author(s)
      Kimura, N
    • Journal Title

      Genes Cells 8・1

      Pages: 65-79

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibition of amino acid-mTOR signaling by a Leucine derivativ induces G1 arrest in Jurkat cells.2003

    • Author(s)
      Hidayat, S.
    • Journal Title

      Biochem.Biophys.Res.Commun. 301・2

      Pages: 417-423

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The mammalian target of rapamycim (mTOR) partoner,rapotor,binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif.2003

    • Author(s)
      Nojima, H.
    • Journal Title

      J.Biol.Chem. 278・18

      Pages: 15461-15464

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Protein-tyrosine phosphatase a, RPTP a, is a Helicobacter pylori VacA receptor.2003

    • Author(s)
      Yahiro, K.
    • Journal Title

      J.Biol.Chem. 278・21

      Pages: 19183-19189

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of TOR-interacting proteins,2003

    • Author(s)
      Yonezawa, K.
    • Journal Title

      Mol.Interv. 3・4

      Pages: 189-193

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ラプター(raputor)2003

    • Author(s)
      米澤 一仁
    • Journal Title

      生化学 75・4

      Pages: 323-323

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 診断と治療性2003

    • Author(s)
      徳永 千春
    • Journal Title

      糖尿病学2003

      Pages: 168-168

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] mTOR/raptor-p70S6キナーゼ2003

    • Author(s)
      米澤 一仁
    • Journal Title

      栄養評価と治療 20・2

      Pages: 179-201

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 細胞成長を司る情報伝達システムの中央情報集積装置mTOR複合体2003

    • Author(s)
      吉野 健一
    • Journal Title

      蛋白質核酸酵素 48・10

      Pages: 1378-1385

    • NAID

      40005884433

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] アミノ酸と細胞内シグナル伝達-蛋白質合成を中心に2003

    • Author(s)
      大城 紀子
    • Journal Title

      栄養評価と治療 20・5

      Pages: 478-482

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway.2003

    • Author(s)
      Naoki, Kimura
    • Journal Title

      Genes Cells 8-1

      Pages: 65-79

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibition of amino acid-mTOR signaling by a leucine derivative induces G1 arrest in Jurkat cells.2003

    • Author(s)
      Sujuti, Hidayat
    • Journal Title

      Biochem.Biophys Res.Commun. 301-2

      Pages: 417-423

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The mammalian target of rapamycin (mTOR) partner, rapter, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif.2003

    • Author(s)
      Hiroki, Nojima
    • Journal Title

      J.Biol.Chem. 278-18

      Pages: 15461-15464

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Protein-tyrosine phosphatase α,RPTP α,is a Helicobacter pylori VacA receptor.2003

    • Author(s)
      Kinnosuke, Yahiro
    • Journal Title

      J.Biol.Chem. 278-21

      Pages: 19183-19189

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of TOR-interacting proteins.2003

    • Author(s)
      Kazuyoshi, Yonezawa
    • Journal Title

      Mol.Interv. 3-4

      Pages: 189-193

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] raptor.2003

    • Author(s)
      Kazuyoshi, Yonezawa
    • Journal Title

      Seikagaku 75-4

      Pages: 323-323

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] mTOR signaling network and insulin action2003

    • Author(s)
      Chiharu, Tokunaga
    • Journal Title

      Tonyobyogaku 2003

      Pages: 21-31

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] mTOR/raptor-p 70S6 kinase.2003

    • Author(s)
      Kazuyoshi, Yonezawa
    • Journal Title

      Jpn.J.Nutr.Assess. 20-2

      Pages: 179-201

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] mTOR complex as an integrating controller of cell growth.2003

    • Author(s)
      Ken-ichi, Yoshino
    • Journal Title

      Tanpakushitsu Kakusan Koso 48-10

      Pages: 1378-1385

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of protein synthesis by amino acid-dependent signaling system.2003

    • Author(s)
      Noriko, Oshiro
    • Journal Title

      Jpn.J.Nutr.Assess. 20-5

      Pages: 478-482

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif.2003

    • Author(s)
      Nojima, H.
    • Journal Title

      J.Biol.Chem. 278・18

      Pages: 15461-15464

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Protein-tyrosine phosphatase α, RPTP α, is a Helicobacter pylori VacA receptor.2003

    • Author(s)
      Yahiro, K.
    • Journal Title

      J.Biol.Chem. 278・21

      Pages: 19183-19189

    • Related Report
      2004 Annual Research Report
  • [Book] TOR : Target of Rapamycin(Curr.Top.Microbiol.Immunol.)2004

    • Author(s)
      Yonezawa, K.
    • Total Pages
      366
    • Publisher
      Springer-Verlag
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] TOR : Target of Rapamycin (Curr.Top.Microbiol.Immunol.)2004

    • Author(s)
      Yonezawa, K.
    • Total Pages
      366
    • Publisher
      Springer-Verlag
    • Related Report
      2004 Annual Research Report
  • [Book] 糖尿病学 20032003

    • Author(s)
      徳永 千春
    • Total Pages
      168
    • Publisher
      診断と治療社
    • Related Report
      2004 Annual Research Report
  • [Publications] Nojima, H.: "The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif"Journal of Biological Chemistry. 278・18. 15461-15464 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yahiro, K.: "Protein-tyrosine phosphatase α, RPTP α, is a Helicobacter pylori VacA receptor"Journal of Biological Chemistry. 278・21. 19183-19189 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 吉野 健一: "細胞成長を司る情報伝達システムの中央情報集積装置mTOR複合体"蛋白質 核酸 酵素. 48・10. 1378-1385 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 大城 紀子: "アミノ酸と細胞内シグナル伝達-蛋白質合成を中心に"栄養評価と治療. 20・5. 478-482 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yonezawa, K.: "Raptor, binding partner of target of rapamycin"Biochemical and Biophysical Research Communications. 313・2. 437-441 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tokunaga, C.: "mTOR integrates amino acid- and energy-sensing pathways"Biochemical and Biophysical Research Communications. 313・2. 443-446 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 徳永 千春: "ラパマイシン標的タンパク質mTORシグナル伝達系"細胞工学. 23・3. 340-348 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Oshiro, N.: "Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function"Genes to Cells. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] 徳永 千春: "糖尿病学2003"(株)診断と治療社. 168 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yonezawa, K.: "TOR : Target of Rapamycin (Current Topics in Microbiology and Immunology)"Springer-Verlag. 366 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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