Ras,PI(3) K和mTOR信号控制瘤细胞的生长
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
概括
细胞通过mTOR信号传递将生长与营养的可用性联系起来. 对于这一过程至关重要的Ras和PI(3) K通路的突变在癌症中很常见,这表明它在瘤发育中发挥了作用.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
背景情况:
- 细胞必须协调生长与环境营养水平.
- mTOR蛋白激酶作为细胞生长的中心调节剂.
- mTOR集成了来自生长因子 (通过Ras和PI(3) K) 和营养可用性 (氨基酸,葡萄糖,氧气) 的信号.
研究的目的:
- 突出mTOR在将细胞生长与营养可用性联系起来的关键作用.
- 强调Ras和PI(3) K信号通路在生长控制中的重要性.
- 提出这些途径的失调有助于瘤发生.
主要方法:
- 审查参与细胞生长调节的信号通路.
- 对人类癌症突变的分析.
- 整合营养感应和细胞生长控制数据.
主要成果:
- mTOR是整合生长因子和营养信号的关键节点.
- 在人类癌症中,Ras和PI(3) K通路组件经常发生突变.
- 这些突变破坏了生长控制检查点.
结论:
- 失去生长控制检查点和在营养限制下增强细胞存活率可能对癌症发展至关重要.
- 拉斯,PI(3) K和mTOR通路的相互联系强调了它们在瘤发生中的重要性.
- 了解这些途径对于癌症研究和治疗策略至关重要.
相关概念视频
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...


