相关实验视频
Updated: Jun 30, 2026

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Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
阿克特/PKB的酸化和调节由rictor-mTOR复合体进行
D D Sarbassov1, David A Guertin, Siraj M Ali
1Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA.
概括
拉巴胺素 (TOR) 复合物的标,包括鱼和哺乳动物TOR (mTOR),对于Ser473.3的Akt/蛋白激酶B (PKB) 酸化至关重要. 这种复合物可能是缺乏PTEN的癌症的治疗点.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 在瘤学瘤学.
背景情况:
- Akt/蛋白激酶B (PKB) 途径的放松调节与癌症和糖尿病有关.
- 激活Akt/PKB需要PDK1在Thr308酸化,而Ser473则需要一个未知的激酶酸化.
研究的目的:
- 为了确定负责Akt/PKB Ser473酸化的激酶.
- 调查拉巴胺复合体 (TOR) 标在 Akt/PKB 激活中的作用.
主要方法:
- 实验在多虫和人类细胞中进行.
- 对鱼和哺乳动物TOR (mTOR) 表达和功能的分析.
- 通过Rictor-mTOR复合体对Akt/PKB进行体外酸化试验.
主要成果:
- 里克托和mTOR对于Akt/PKB Ser473酸化至关重要.
- 减少了rictor或mTOR表达抑制了Akt/PKB效应器活性.
- 瑞克托-mTOR复合物在Ser473直接化了Akt/PKB,并通过PDK1.1促进了Thr308的化.
结论:
- 里克托-mTOR复合体是负责Akt/PKB Ser473酸化的激酶.
- 瑞克托-mTOR作为Akt/PKB激活的关键调节者.
- 在PTEN缺陷瘤中,Rictor-mTOR代表了一个潜在的治疗标.
相关概念视频
Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
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...
Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
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...
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...

