在mTOR路径的结构机制
Karen Y Linde-Garelli1, Kacper B Rogala1
1Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA; Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Current opinion in structural biology
|August 12, 2023
概括
拉巴胺素 (mTOR) 途径的机械标调节细胞生长和新陈代谢. 结构研究揭示了mTOR复合物如何在膜上被激活,为疾病和潜在治疗提供了洞察力.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 拉巴胺素 (mTOR) 信号通路的机械性标对于调节哺乳动物细胞生长,增殖和新陈代谢至关重要.
- mTOR存在于两个不同的复合体,mTORC1和mTORC2,每一个都有独特的下游目标和功能.
- mTOR通路的调节失调与各种疾病有关,包括癌症和代谢障碍.
研究的目的:
- 阐明 mTOR 路径调节的基础结构机制.
- 了解mTOR复合体是如何组装,局部化到膜,并激活的.
- 探索针对治疗开发的mTOR途径的翻译潜力.
主要方法:
- 最近的结构研究采用了冷电子显微镜和X射线晶体学等技术.
- 生物化学试验用于研究蛋白质与蛋白质相互作用和基质招募.
- 细胞成像来追踪mTOR复杂的定位和动态.
主要成果:
- 详细的分子洞察力如何信号输入调节mTOR复杂组装和激活.
- 描述mTOR复合体被招募到生物膜中的机制,并在生物膜中发挥作用.
- 确定涉及基质结合和酸化的关键结构特征.
结论:
- 一个全面的了解mTOR结构机制正在出现.
- 这种知识对于破译mTOR在健康和疾病中的作用至关重要.
- 结构性洞察力正在为开发新的mTOR向治疗方法铺平道路.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.7K
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...
3.7K
mTOR Signaling and Cancer Progression
3.8K
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...
3.8K
Interactions Between Signaling Pathways
6.3K
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...
6.3K
MAPK Signaling Cascades
5.7K
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...
5.7K
The JAK-STAT Signaling Pathway
9.0K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
9.0K
Regulation of Expression Occurs at Multiple Steps
22.8K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.8K


