转化抑制剂PHAS-I的酸化由哺乳动物目标的拉帕素
G J Brunn1, C C Hudson, A Sekulić
1Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Science (New York, N.Y.)
|July 4, 1997
概括
免疫抑制药物拉巴胺通过阻断哺乳动物目标拉巴胺 (mTOR) 激酶来抑制细胞循环的进展. 这种作用防止PHAS-I的酸化,PHAS-I是一种控制蛋白质合成的关键蛋白质.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 拉帕米辛是一种免疫抑制剂,可以阻止细胞循环的进展.
- 哺乳动物的目标拉巴胺素 (mTOR) 是一个关键的信号蛋白,参与细胞生长和增殖.
- mTOR作为终端激酶,在细胞刺激与蛋白质合成调节的途径中起作用.
研究的目的:
- 阐明mTOR在调节细胞周期进展中的作用.
- 调查拉巴胺抑制G1阶段进展的机制.
- 定义mTOR在翻译控制中的功能.
主要方法:
- 研究了拉巴胺对淋巴细胞和其他细胞类型G1相进展的影响.
- 确定了mTOR在调节PHAS-I酸化的信号通路中的位置.
- 研究了对胰岛素刺激细胞中PHAS-I酸化的拉巴素敏感mTOR激酶活性的要求.
- 通过mTOR进行了PHAS-I的体外酸化试验.
主要成果:
- 拉帕米辛通过抑制mTOR功能来抑制G1阶段的进展.
- mTOR是一种终端酶,将线性刺激与PHAS-I酸化合起来.
- 对于响应胰岛素的PHAS-I酸化,mTOR激酶活性是必不可少的.
- mTOR在氨酸和氨酸残留物上化PHAS-I.
- 通过mTOR的PHAS-I酸化抑制了它与真核生物启动因子 (eIF) -4E的结合.
结论:
- mTOR在翻译控制中起着至关重要的作用.
- 拉巴胺素对G1阶段进展的抑制是由其对mTOR及其随后的翻译调节的影响来介导的.
- 这些发现提供了对拉帕素对细胞循环进展作用的分子机制的洞察.
相关概念视频
01:02Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
01:02Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
03:03mTOR 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...
01:07MAPK 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...
01:20The JAK-STAT Signaling Pathway
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...
01:22PI3K/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...