mTORC1のリン酸化部位は,飢餓とラパミシンに対する感受性をコードする
Seong A Kang1, Michael E Pacold, Christopher L Cervantes
1Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
Science (New York, N.Y.)
|July 27, 2013
まとめ
ラパマイシン (mTOR) 複合体1 (mTORC1) 経路のメカニズム的標的
科学分野:
- 細胞の信号伝達経路は,
- 細胞成長調節の分子メカニズム
背景:
- ラパミシン (mTOR) 複合体1 (mTORC1) のメカニスティックターゲットは,細胞成長の重要な調節因子である.
- ラパミシンは,mTORC1を標的とした薬で,モデル生物の寿命を延ばしますが,基板のリン酸化への影響は完全に理解されていません.
研究 の 目的:
- 特定のmTORC1基板がラパミシンに耐性がある理由を調査する.
- mTORC1経路調節器に対する基板感受性の決定因子を特定する.
主な方法:
- mTORC1のリン酸化部位を代表するペプチドを用いたインビトロキナーゼアッセイ.
- ラパミシンと飢餓に対する基質のリン酸化感受性を評価する細胞実験.
主要な成果:
- mTORC1キナーゼの活性度は,異なるリン酸化部位によって著しく変化します.
- 実験室内活性性は,ラパミシンに対する細胞内耐性および飢餓と強く相関しています.
- リン酸化部位の軽微な変化は,mTORC1の活性と経路調節剤に対する細胞の感受性を変化させます.
結論:
- リン酸化部位がmTORC1基質として作用する本質的な能力として定義される基質の質は,ラパミシンと飢餓に対する感受性の重要な決定因子です.
- この発見は,mTORC1エフェクタを共通の信号によって差異調節するメカニズムを示しています.
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