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mTOR Signaling and Cancer Progression03:03

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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...
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PI3K/mTOR/AKT Signaling Pathway01:22

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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...
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Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

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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...
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Mitogens and the Cell Cycle02:38

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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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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...
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Amplifying Signals via Enzymatic Cascade01:22

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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成長制御におけるmTOR基板のリン酸化

Stefania Battaglioni1, Don Benjamin1, Matthias Wälchli1

  • 1Biozentrum, University of Basel, Spitalstrasse 41, 4056 Basel, Switzerland.

Cell
|May 17, 2022
PubMed
まとめ
この要約は機械生成です。

ラパミシン (TOR) キナーゼの標的は細胞の成長と代謝を調節する. 哺乳類のTOR複合体mTORC1とmTORC2は,触媒のサブユニットを共有しているにもかかわらず,共通のモチーフを使用して異なる基板をリン酸化します.

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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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科学分野:

  • 分子生物学
  • 細胞の代謝
  • 生物化学

背景:

  • ラパミシン (TOR) の標的は,細胞の成長と代謝を調節する重要なセリン/スレオニンキナーゼです.
  • TOR信号は栄養素,成長因子,細胞のエネルギーレベルによって活性化されます.
  • TORは2つの異なる複合体,TORC1とTORC2で存在し,異なる機能を持っています.

研究 の 目的:

  • 哺乳類のTOR (mTOR) の直接基板をすべて検討し,特定する.
  • mTORC1とmTORC2が異なる基質をリン酸化する方法を明らかにする.
  • 構造データに基づくmTOR複合体による基質採用メカニズムを理解する.

主な方法:

  • mTORシグナルに関する包括的な文献レビュー.
  • 直接的なmTOR基板の識別
  • mTOR複合体に関する構造情報の分析

主要な成果:

  • mTORの多くの直接基質を特定した.
  • mTORC1とmTORC2が異なる基板をリン酸化することを示した.
  • 両複合体は共通のリン酸化モチーフを使用することを示した.

結論:

  • mTORC1とmTORC2は,共有した触媒サブユニットにもかかわらず,基板特異性を示す.
  • この2つの複合体は異なるメカニズムで異なる基質を集めます.
  • 両方のmTOR複合体によって共通の最小モチーフがリン酸化され,調整された調節を示す.