mTORはラプターと相互作用して,細胞成長機構に信号を送る栄養素に敏感な複合体を形成します
Do-Hyung Kim1, D D Sarbassov, Siraj M Ali
1Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
Cell
|August 2, 2002
まとめ
ラパミシン (mTOR) 経路のメカニスティックターゲットは,細胞の成長を調節する. この研究は,mTORと複合体を形成し,栄養素の利用可能性に基づいて細胞サイズを制御する重要なタンパク質としてラプターを特定しています.
科学分野:
- 細胞生物学 細胞生物学
- 分子シグナリング
- バイオケミストリー バイオケミストリー
背景:
- ラパミシン (mTOR) 経路のメカニズム的ターゲットは,栄養素やホルモンに対する反応として細胞成長の調節に不可欠です.
- mTORは,免疫抑制薬ラパミシンの標的である.
- mTORが栄養分レベルを感知する正確なメカニズムは,まだ完全に理解されていません.
研究 の 目的:
- mTORシグナル伝達経路における保存タンパク質ラプターの役割を調査する.
- ラプターがmTORとどのように相互作用し,その活動に影響を与えるかを明らかにする.
- mTOR-ラプター複合体の栄養素感知と細胞サイズ調節への貢献を決定する.
主な方法:
- mTORとラプター間のタンパク質複合体の形成の生化学分析.
- 様々な栄養条件下でのmTORキナーゼ活性を測定するためのアッセイ.
- S6K1や細胞サイズなどの下流効果因子に対するラプターの影響に関する研究.
主要な成果:
- mTORは,mTOR経路の保存されたタンパク質であるラプターとステキオメトリック複合体を形成します.
- ラプターは,S6K1,細胞サイズ維持,およびmTORタンパク質発現に対する栄養素刺激信号を正面に調節する.
- ラプターとmTORの結合は,mTORキナーゼの活性を否定的に調節する.
- 栄養素欠乏とミトコンドリア解離はmTOR-ラプター複合体を安定させ,mTORキナーゼの活性を抑制する.
結論:
- ラプターは,mTOR経路の重要な構成要素であり,栄養素の利用可能性のセンサーとして機能します.
- mTOR-ラプター複合体は,栄養分レベルに応じて細胞サイズを調節する上で重要な役割を果たします.
- mTOR-ラプター相互作用の理解は,細胞成長制御と潜在的な治療標的の洞察を提供します.
関連する概念動画
mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Receptor Tyrosine Kinases
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...


