Ras,PI(3) K,mTORのシグナリングは,腫瘍細胞の成長を制御する
Reuben J Shaw1, Lewis C Cantley
1Dulbecco Laboratory for Cancer Research, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, California 9203, USA. shaw@salk.edu
Nature
|May 26, 2006
まとめ
ユカリオット細胞は,mTORシグナル伝達を通じて,成長と栄養素の供給を結びつける. このプロセスに不可欠なRasとPI(3) K経路の変異は,がんでは一般的であり,腫瘍発達の役割を示唆しています.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- 癌生物学 癌生物学について
背景:
- ユカリオット細胞は,成長と環境の栄養分レベルを調整しなければなりません.
- mTORタンパク質キナーゼは,細胞成長の中央調節剤として作用する.
- mTORは,成長因子 (RasとPI(3) K経由) と栄養素の利用可能性 (アミノ酸,グルコース,酸素) の信号を統合しています.
研究 の 目的:
- 細胞の成長と栄養素の供給を結びつける上でmTORの重要な役割を強調する.
- 成長制御におけるRasとPIのシグナル伝達経路の重要性を強調する.
- これらの経路の不調が腫瘍発生に寄与することを提案する.
主な方法:
- 細胞成長の調節に関与する信号伝達経路のレビュー.
- 人間のがんにおける変異の分析.
- 栄養素センシングと細胞成長制御に関するデータの統合.
主要な成果:
- mTORは,成長因子と栄養信号を統合するキーノードです.
- RasとPI(3) K経路のコンポーネントは,ヒトの癌で頻繁に変異する.
- これらの変異は,成長制御のチェックポイントを乱します.
結論:
- 成長制御チェックポイントの喪失と栄養素の制限下で細胞生存の強化は,がんの発症に不可欠である可能性が高い.
- Ras,PI(3) K,mTOR経路の相互接続性は,腫瘍発生におけるその重要性を強調しています.
- これらの経路を理解することは,がん研究と治療戦略において極めて重要です.
関連する概念動画
The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
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...
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...


