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Regulation mechanisms of mTOR-mediated nutrient signaling by protein phosphatase PP2A

Research Project

Project/Area Number 20390081
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionKobe University

Principal Investigator

KIKKAWA Ushio  Kobe University, 自然科学系先端融合研究環バイオシグナル研究センター, 教授 (40150354)

Co-Investigator(Kenkyū-buntansha) KAMADA Shinji  神戸大学, 自然科学系先端融合研究環バイオシグナル研究センター, 准教授 (20243214)
OSHIRO Noriko  神戸大学, 自然科学系先端融合研究環バイオシグナル研究センター, 助教 (70372662)
NAKASHIMA Akio  神戸大学, 自然科学系先端融合研究環バイオシグナル研究センター, 助教 (70397818)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2009: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2008: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Keywordsシグナル伝達 / mTOR / 栄養 / ホスファターゼ / ラパマイシン / AMPK / mTIP41 / アミノ酸 / PP242 / TIP41 / Rheb / STAT3
Research Abstract

We studied the involvement of the protein dephosphorylation reaction in the regulation of the protein kinase named mTOR, that senses the intracellular concentrations of amino acids to control cell proliferation. It was revealed that mTIP41, a regulator of the protein dephosphorylation reaction, enhances the mTOR signaling pathway by not only suppressing the dephosphorylation of mTOR substrates but also playing a role in the upstream of the mTOR protein kinase. These results of nutrient signaling are important to elucidate the cellular regulation mechanisms by amino acids.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (36 results)

All 2011 2010 2009 2008 Other

All Journal Article (19 results) (of which Peer Reviewed: 16 results) Presentation (15 results) Remarks (2 results)

  • [Journal Article] Contribution of caspase(s) to the cell cycle regulation at mitotic phase.2011

    • Author(s)
      Hashimoto, T., Kikkawa, U., Kamada, S.
    • Journal Title

      PLoS ONE 6(3)

    • NAID

      120005465546

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Contribution of caspase(s) to the cell cycle regulation at mitotic phase.2011

    • Author(s)
      Hashimoto, T.
    • Journal Title

      PLoS ONE

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] アミノ酸センシングのシステムとしてのmTORC複合体1の機序2011

    • Author(s)
      原賢太
    • Journal Title

      実験医学

      Volume: 29 Pages: 865-870

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Signal transducer and activator of transcription 3 upregulates interleukin-8 expression at the level of transcription in human melanoma cells.2010

    • Author(s)
      Oka, M., Sakaguchi, M., Okada, T., Nagai, H., Ozaki, M., Yoshioka, T., Inoue, H., Mukaida, N., Kikkawa, U., Nishigori, C.
    • Journal Title

      Exp.Dermatol. 19(8)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mammalian Tti1 and Tel2 are critical factors in mTOR complex assembly.2010

    • Author(s)
      Kaizuka, T., Hara, T., Oshiro, N., Kikkawa, U., Yonezawa, K., Takehana, K., Iemura, S.I., Natsume, T., Mizushima, N.
    • Journal Title

      J.Biol.Chem. 285(26)

      Pages: 20109-20116

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mammalian Ttil and Te12 are critical factors in mTOR complex assembly.2010

    • Author(s)
      Kaizuka, T.
    • Journal Title

      J.Biol.Chem.

      Volume: 285 Pages: 20109-20116

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signal transducer and activator of transcription 3 upregulates interleukin-8 expression at the level of transcription in human melanoma cells2010

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

      Exp.Dermatol. (印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AMP-activated protein kinase phosphorylates glutamine : fructose-6-phosphate amidotransferase 1 at Ser243 to modulate its enzymatic activity.2009

    • Author(s)
      Eguchi, S., Oshiro, N., Miyamoto, T., Yoshino, K., Okamoto, S., Ono, T., Kikkawa, U., Yonezawa, K.
    • Journal Title

      Genes Cells 14(2)

      Pages: 179-189

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activation of mTORC1 in two steps : Rheb-GTP activation of catalytic function and increased binding of substrates to raptor.2009

    • Author(s)
      Avruch, J., Long, X., Lin, Y., Ortiz-Vega, S., Rapley, J., Papageorgiou, A., Oshiro, N., Kikkawa, U.
    • Journal Title

      Biochem.Soc.Trans. 37(1)

      Pages: 223-226

    • Related Report
      2010 Final Research Report
  • [Journal Article] AMP-activated protein kinase phosphorylates glutamine : fructose-6-phosphate amidotransferase l at Ser243 to modulate its enzymatic activity.2009

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

      Genes Cells 14

      Pages: 179-189

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of mTORCl in two steps : Rheb-GTP activation of catalytic function and increased binding of substrates to raptor.2009

    • Author(s)
      Avruch, J.
    • Journal Title

      Biochem. Soc. Trans. 37

      Pages: 223-226

    • Related Report
      2008 Annual Research Report
  • [Journal Article] AMP-activated protein kinase phosphorylates Golgi-specific brefeldin A resistance factor 1 at Thr1337 to induce disassembly of Golgi apparatus.2008

    • Author(s)
      Miyamoto, T., Oshiro, N., Yoshino, K., Nakashima, A., Eguchi, S., Takahashi, M., Ono, Y., Kikkawa, U., Yonezawa, K.
    • Journal Title

      J.Biol.Chem. 283(7)

      Pages: 4430-4438

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Calcineurin- mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation.2008

    • Author(s)
      Huang, C.C, Wang, J.M., Kikkawa, U., Mukai, H., Shen, M.R., Morita, I., Chen, B.K., Chang, W.C.
    • Journal Title

      Oncogene 27(17)

      Pages: 2422-2429

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of caspase-7 in cell cycle progression at mitosis.2008

    • Author(s)
      Hashimoto, T., Yamauchi, L., Hunter, T., Kikkawa, U., Kamada, S.
    • Journal Title

      Genes Cells 13(6)

      Pages: 609-621

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The yeast Tor signaling pathway is involved in G2/M transition via polo-kinase.2008

    • Author(s)
      Nakashima, A., Maruki, Y., Imamura, Y., Kondo, C., Kawamata, T., Kawanishi, I., Takata, H., Matsuura, A., Lee, K.S., Kikkawa, U., Ohsumi, Y., Yonezawa, K., Kamada, Y.
    • Journal Title

      PLoS ONE 3(5)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation.2008

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

      Oncogene 27

      Pages: 2422-2429

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AMP-activated protein kinase phosphorylates Golgi-specific brefeldin A resistance factor I at Thr1337 to induce disassembly of Golgi apparatus.2008

    • Author(s)
      Miyamoto, T.
    • Journal Title

      J. Biol. Chem. 283

      Pages: 4430-4438

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of caspase-7 in cell cycle progression at mitosis.2008

    • Author(s)
      Hashimoto, T.
    • Journal Title

      Genes Cells 13

      Pages: 609-621

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The yeast Tor signaling pathway is involved in G2/M transition via polo-kinase.2008

    • Author(s)
      Nakashima, A.
    • Journal Title

      PLoS ONE 3

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Organization and closing remarks.2011

    • Author(s)
      吉川潮
    • Organizer
      2011 International Symposium on Cell Signaling and Gene Regulation.
    • Place of Presentation
      National Cheng Kung University, Tainan, Taiwan
    • Related Report
      2010 Final Research Report
  • [Presentation] Cdk5は結合する制御サブユニット、p35、p39又はCyclinI、により異なった細胞内局在を示す2010

    • Author(s)
      三橋真海子
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] 分裂酵母TORC1によるS6キナーゼPsk1の制御2010

    • Author(s)
      中嶋昭雄
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Caspase-3,6,7により切断されるプロテインカイネースの比較2010

    • Author(s)
      林祥太
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] カスパーゼの活性化阻害による細胞増殖の異常2010

    • Author(s)
      橋本季明
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] Screening of novel caspase substrates functioning at mitotic phase2009

    • Author(s)
      橋本季明
    • Organizer
      第32回日本分子生物学会年会(BMB2009)
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] Opening Remarks, The signaling mechanisms through the protein phosphorylation reaction2009

    • Author(s)
      Kikkawa, U.
    • Organizer
      2009 Japan-Taiwan Joint Symposium on Cell Signaling and Gene Regulation
    • Place of Presentation
      Kobe International Conference Center, Kobe, Japan
    • Year and Date
      2009-11-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] The signaling mechanisms through the protein phosphorylation reaction.2009

    • Author(s)
      吉川潮
    • Organizer
      2009 Japan-Taiwan Joint Symposium on Cell Signaling and Gene Regulation.
    • Place of Presentation
      Kobe International Conference Center, Kobe, Japan,
    • Related Report
      2010 Final Research Report
  • [Presentation] Screening of novel caspase substrates functioning at mitotic phase.2009

    • Author(s)
      橋本季明、吉田茂生、澤崎達也、遠藤弥重太、吉川潮、鎌田真司
    • Organizer
      第32回日本分子生物学会年会(BMB2009)
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 細胞分裂制御における活性化caspase-7の役割2008

    • Author(s)
      橋本季明
    • Organizer
      第31回日本分子生物学会、第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2008-12-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] Identification of phosphoproteins in nutritional signaling by the combination of the immunoprecipitation using the phosphorylation-site specific antibody and mass fingerprinting analvsis.2008

    • Author(s)
      Kikkawa, U.
    • Organizer
      2008 International Symposium on Cell Signaling and Gene Regulation.
    • Place of Presentation
      Tainan, Taiwan
    • Year and Date
      2008-11-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] The regulation of GFATl via AMPK signaling.2008

    • Author(s)
      Eguchi, S.
    • Organizer
      第60回日本細胞生物学会大会
    • Place of Presentation
      パシフイコ横浜
    • Year and Date
      2008-06-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] The regulation of GFAT1 via AMPK signaling.2008

    • Author(s)
      Eguchi, S., Oshiro, N., Miyamoto, T., Sasaki, T., Yonezawa, K., Kikkawa U.
    • Organizer
      第60回日本細胞生物学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] Identification of phosphoproteins in nutritional signaling by the combination of the immunoprecipitation using the phosphorylation-site specific antibody and mass fingerprinting analysis.2008

    • Author(s)
      吉川潮
    • Organizer
      2008 International Symposium on Cell Signaling and Gene Regulation
    • Place of Presentation
      National Cheng Kung University, Tainan, Taiwan
    • Related Report
      2010 Final Research Report
  • [Presentation] カスパーゼの活性化阻害による細胞増殖の異常2008

    • Author(s)
      橋本季明、吉川潮、鎌田真司
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ

    • URL

      http://www.biosig.kobe-u.ac.jp/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.biosig.kobe-u.ac.jp/lab_2.html

    • Related Report
      2010 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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