関連する実験動画
Updated: Jun 30, 2026

11:13
Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
リクター-mTOR複合体によるAkt/PKBのリン酸化と調節
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.
まとめ
ラパミシン (TOR) 複合体の標的は,リクターと哺乳類のTOR (mTOR) を含むが,Ser473.3でAkt/タンパク質キナーゼB (PKB) のリン酸化に不可欠である. この複合体は,PTENが欠けているがんの治療標的である可能性があります.
科学分野:
- 分子生物学は分子生物学である.
- 細胞シグナル伝達 細胞信号伝達
- 腫瘍学 腫瘍学
背景:
- Akt/タンパク質キナーゼB (PKB) 経路の緩和は,がんや糖尿病と関連しています.
- Akt/PKBの活性化には,PDK1によるThr308のリン酸化と,未知のキナーゼによるSer473のリン酸化が必要です.
研究 の 目的:
- Akt/PKB Ser473のリン酸化に起因するキナーゼを特定する.
- Akt/PKB活性化におけるラパミシン (TOR) 複合体の標的の役割を調査する.
主な方法:
- ドロソフィラとヒトの細胞で実施された実験.
- リクターと哺乳類のTOR (mTOR) 発現と機能の分析.
- リクター-mTOR複合体によるAkt/PKBのインビトロリン酸化測定.
主要な成果:
- RictorとmTORは,Akt/PKB Ser473のリン酸化に不可欠である.
- リクターまたはmTOR発現の減少は,Akt/PKBエフェクター活性を抑制する.
- リクター-mTOR複合体は,Ser473でAkt/PKBを直接リン酸化し,PDK1.1によってThr308のリン酸化を促進した.
結論:
- リクトル-mTOR複合体は,Akt/PKB Ser473のリン酸化を司るキナーゼである.
- Rictor-mTORは,Akt/PKBの活性化の重要な調節剤として作用する.
- Rictor-mTORは,PTEN欠乏性腫瘍における潜在的な治療標的を代表しています.
関連する概念動画
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...

