Studies of PRAS40, the novel substrate of mTOR that senses the nutritional environments and regulates cellular functions

• Project/Area Number: 19790213
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Kobe University
• Principal Investigator: OSHIRO Noriko 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, 助教 (70372662)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 細胞内シグナル伝達 / 栄養化学 / アミノ酸 / mTOR / ラパマイシン / プロテインキナーゼ / PRAS40 / リン酸化部位特異的抗体

Research Abstract

mTORは免疫抑制剤ラパマイシンの細胞内標的として同定されたプロテインキナーゼであり、アミノ酸濃度の上昇により活性化され翻訳調節因子である4E-BP1およびS6Kのリン酸化を介してタンパク合成を制御している。本研究では第3のmTOR 基質としてPRAS40を同定し、mTORによるリン酸化残基(Ser183)を決定した。PRAS40 はタンパク合成調節以外のmTORによる細胞機能制御に関与する可能性が高く、今後、その機能解明が重要な課題である。

Research Products

• [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 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 Pages: 223-226
• [Journal Article] Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy (2009)
  • Author(s): Hosokawa N., Hara T., Kaizuka T., Kishi C., Takamura A., Miura Y., Iemura S. I., Natsume T., Takehana K., Yamada N., Guan J. L., Oshiro N., Mizushima N.
  • Journal Title: Mol. Biol. Cell (in press)
  • Peer Reviewed
• [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 Pages: 4430-4438
  • Peer Reviewed
• [Journal Article] The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1 (2007)
  • Author(s): Oshiro N., Takahashi R., Yoshino K., Tanimura K., Nakashima A., Eguchi S., Miyamoto T., Hara K., Takehana K., Avruch J., Kikkawa U., Yonezawa K.
  • Journal Title: J. Biol. Chem. 282 Pages: 20329-20339
  • Peer Reviewed
• [Journal Article] Identification of TBC7 having TBC domain as a novel binding protein to TSC1-TSC2 complex (2007)
  • Author(s): Nakashima A., Yoshino K., Miyamoto T., Eguchi S., Oshiro N., Kikkawa U., Yonezawa K.
  • Journal Title: Biochem Biophys Res Commun 361 Pages: 218-223
  • Peer Reviewed
• [Journal Article] The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1 (2007)
  • Author(s): Oshiro, N.
  • Journal Title: J. Biol. Chem. 282・28 Pages: 20329-20339
  • Peer Reviewed
• [Journal Article] Identification of TBC7 having TBC domain as a novel binding protein to TSC1-TSC2 complex (2007)
  • Author(s): Nakashima, A.
  • Journal Title: Biochem. Biophys. Res. Commun. 361・1 Pages: 218-223
  • Peer Reviewed
• [Journal Article] AMP-activated protein kinase phosphorylates Golgi-specific brefeldin A resistance fector 1 at Thrl337 to induce disassembly of Golgi apparatus (2007)
  • Author(s): Miyamoto, T.
  • Journal Title: J. Biol. Chem. 283・7 Pages: 4430-4438
  • Peer Reviewed
• [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
• [Presentation] Identification of PRAS40 (Proline-Rich Akt Substrate of 40 kDa) as a novel substrate of mTORC1 (2007)
  • Author(s): 大城 紀子
  • Organizer: Biochemistry and Molecular Biology 2007
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-12
• [Presentation] Identification of PRAS40 (Proline-Rich Akt Substrate of 40 kDa) as a novel substrate of mTORC1 (2007)
  • Author(s): 大城紀子, 吉川 潮
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学大会合同大会(BMB2007)
• [Presentation] AMPKの新規基質GFAT1の同定と機能解析 (2007)
  • Author(s): 江口賢史, 大城紀子, 米澤一仁, 吉川 潮
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学大会合同大会(BMB2007)
• [Presentation] AMPK regulates the morphology of Golgi through the phosphorylation of GBF1 (2007)
  • Author(s): 宮本嵩史, 大城紀子, 米澤一仁, 吉川 潮
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学大会合同大会(BMB2007)