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相关概念视频

The Ras Gene02:38

The Ras Gene

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The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
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Small GTPases - Ras and Rho01:24

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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
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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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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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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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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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相关实验视频

Updated: Jul 19, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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直接调节K-Ras膜相互作用的直接调节器.

Johannes Morstein1, Rebika Shrestha2, Que N Van2

  • 1Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California, San Francisco, California 94158, United States.

ACS chemical biology
|August 14, 2023
PubMed
概括

研究人员通过将脂质尾巴与K-Ras(G12C) 结合剂结合来调节蛋白质膜相互作用 (PMI). 这一策略改变了K-Ras (G12C) 形状和细胞膜相互作用,影响了信号通路.

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Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein
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Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
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科学领域:

  • 生物化学 生物化学
  • 细胞生物学 细胞生物学
  • 分子药理学分子药理学

背景情况:

  • 蛋白质膜相互作用 (PMI) 对细胞信号传输至关重要,特别是在启动信号转导级联时.
  • 暂时和动态的PMI调节了内部等离子体膜的信号热点.

研究的目的:

  • 开发一种直接准和调节蛋白质膜相互作用的方法.
  • 研究脂质结合对K-Ras (G12C) 行为和细胞信号传递的影响.

主要方法:

  • 一个中链脂质尾部与K-Ras (((G12C) 共价结合剂MRTX849.9的结合.
  • 分子动力学 (MD) 模拟和NMR研究,以分析形状变化.
  • 细胞测试以评估K-Ras (G12C) 横向移动性和纳米集群的形成.

主要成果:

  • 脂质结合通过改变K-Ras (G12C) 膜的方向和形状,成功调节了PMI.
  • 修改后的结合剂限制了K-Ras (G12C) 在细胞内的横向运动.
  • 观察到K-Ras ((G12C) 纳米集群的破坏.

结论:

  • 脂质结合是一种可行的策略,可以直接调节短暂的蛋白质膜相互作用.
  • 这种方法提供了一种潜在的方法,通过控制蛋白质定位和信号来开发向治疗方法.
  • 该策略可能广泛适用于其他参与过渡性PMI的蛋白质.