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Analysis of amino acid-dependent signal transduction from transporters to mTOR by cell-free assay system

Research Project

Project/Area Number 26860171
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionOsaka University

Principal Investigator

OKUDA Suguru  大阪大学, 医学(系)研究科(研究院), 助教 (50511846)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsアミノ酸 / シグナル伝達 / mTOR / シグナル情報伝達 / トランスポーター
Outline of Final Research Achievements

We performed experiments to reveal the mechanism of mTORC1 stimulation by amino acids. The main results are described below. 1) The recognition moieties of leucine by an amino acid transporter LAT1, which localizes on the plasma membrane of cancer cells and is a main transporter to take leucine up into cells, were determined by the experiments with various leucine derivatives. The important moieties of leucine to activate mTORC1 were also revealed. 2) We established the cell-free assay to identify important factors for mTOR to sense amino acid availability, and to analyze its molecular mechanism. In this assay system, we could observe the effect of additives for mTOR activity. This system is expected to be used for analyzing how the amino acid sensing relates to cell growth and proliferation.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (9 results)

All 2016 2015 2014

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 4 results) Presentation (5 results)

  • [Journal Article] Transport of 3-fluoro-l-α-methyl-tyrosine (FAMT) by organic ion transporters explains renal background in [(18)F]FAMT positron emission tomography.2016

    • Author(s)
      Wei L, Tominaga H, Ohgaki R, Wiriyasermkul P, Hagiwara K, Okuda S, Kaira K, Kato Y, Oriuchi N, Nagamori S, Kanai Y.
    • Journal Title

      J Pharmacol Sci.

      Volume: 130 Issue: 2 Pages: 101-109

    • DOI

      10.1016/j.jphs.2016.01.001

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Specific transport of 3-fluoro-l-α-methyl-tyrosine by LAT1 explains its specificity to malignant tumors in imaging.2016

    • Author(s)
      Wei L, Tominaga H, Ohgaki R, Wiriyasermkul P, Hagiwara K, Okuda S, Kaira K, Oriuchi N, Nagamori S, Kanai Y.
    • Journal Title

      Cancer Sci.

      Volume: 107 Issue: 3 Pages: 347-352

    • DOI

      10.1111/cas.12878

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Novel cystine transporter in renal proximal tubule identified as a missing partner of cystinuria-related plasma membrane protein rBAT/SLC3A1.2016

    • Author(s)
      Nagamori S, Wiriyasermkul P, Guarch ME, Okuyama H, Nakagomi S, Tadagaki K, Nishinaka Y, Bodoy S, Takafuji K, Okuda S, Kurokawa J, Ohgaki R, Nunes V, Palacín M, Kanai Y.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 113 Issue: 3 Pages: 775-780

    • DOI

      10.1073/pnas.1519959113

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Structure-activity relations of leucine derivatives reveal critical moieties for cellular uptake and activation of mTORC1-mediated signaling.2016

    • Author(s)
      Nagamori S, Wiriyasermkul P, Okuda S, Kojima N, Hari Y, Kiyonaka S, Mori Y, Tominaga H, Ohgaki R, Kanai Y.
    • Journal Title

      Amino Acids.

      Volume: 48 Issue: 4 Pages: 279-286

    • DOI

      10.1007/s00726-015-2158-z

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Leucine transported by a cancer-type amino acid transporter LAT1 affects multiple cellular processes in pancreatic cancer cells2015

    • Author(s)
      Pornparn Kongpracha, Pattama Wiriyasermkul, Noriyoshi Isozumi, Kazuko Kaneda-Nakashima, Suguru Okuda, Ryuichi Ohgaki, Shushi Nagamori, Yoshikatsu Kanai
    • Organizer
      BMB2015 (第38回 日本分子生物学会年会、第88回 日本生化学会大会)
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Transport of 3-fluoro-l-α-methyl-tyrosine (FAMT) by organic ion transporters: a possible cause of renal background in 18F-FAMT PET2015

    • Author(s)
      Wei Ling、富永英之、Wiriyasermkul Pattama、大垣隆一、萩原浩平、奥田傑、永森收志、金井好克
    • Organizer
      第127回 日本薬理学会近畿部会
    • Place of Presentation
      岐阜
    • Year and Date
      2015-06-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Inhibition of the LAT1-mediated leucine transport affects multiple cellular processes in pancreatic cancer cells2015

    • Author(s)
      Pornparn Kongpracha, Pattama Wiriyasermkul, Noriyoshi Isozumi, Printip Wongthai, Suguru Okuda, Kenjiro Tadagaki, Ryuichi Ohgaki, Shushi Nagamori, Yoshikatsu Kanai
    • Organizer
      第62回 日本生化学会近畿支部例会
    • Place of Presentation
      草津
    • Year and Date
      2015-05-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] ロイシンによるmTOR活性化機構解明のためのロイシン誘導体とロイシン結合タンパク質との相互作用解析2015

    • Author(s)
      奥田 傑
    • Organizer
      第88回 日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-03-19
    • Related Report
      2014 Research-status Report
  • [Presentation] ロイシン結合タンパク質との相互作用とmTOR活性化に必要なロイシンの構造部位の同定とその相関2014

    • Author(s)
      奥田 傑
    • Organizer
      第87回 日本生化学会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-18
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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