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

• Project/Area Number: 20390081
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kobe 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: ¥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.

Research Products

• [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
  • 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)
  • 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
• [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)
  • 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
  • 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
  • Peer Reviewed
• [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.
  • Journal Title: Exp.Dermatol. (印刷中)
  • 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
  • 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
• [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
  • 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
• [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
  • 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
  • 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
  • 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)
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [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
• [Presentation] Screening of novel caspase substrates functioning at mitotic phase (2009)
  • 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
• [Presentation] Opening Remarks, The signaling mechanisms through the protein phosphorylation reaction (2009)
  • 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
• [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,
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Remarks] ホームページ
  • URL: http://www.biosig.kobe-u.ac.jp/
• [Remarks]
  • URL: http://www.biosig.kobe-u.ac.jp/lab_2.html