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相关概念视频

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
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Cell-surface Signaling

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Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
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Hedgehog Signaling Pathway02:33

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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Water-soluble hormones cannot cross the plasma membrane, so they rely on protein receptors that span the membrane to trigger intracellular signaling pathways. These pathways then activate second messengers inside the cell, including cAMP or calcium ions.
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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
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Visualization and Quantification of TGF&#946;/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
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FGF激素信号的结构基础

Lingfeng Chen1,2, Lili Fu1,3,4, Jingchuan Sun1,5

  • 1Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.

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|June 7, 2023
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概括
此摘要是机器生成的。

肝素硫酸盐 (HS) 作为一个共受体,使纤维细胞生长因子 (FGF) 激素能够通过不对称的二分化激活FGF受体 (FGFR). 这一发现挑战了现有的模型,并为代谢疾病和癌症提供了新的治疗点.

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科学领域:

  • 生物化学
  • 结构生物学
  • 内分泌学

背景情况:

  • 纤维细胞生长因子 (FGF) 激素需要αKlotho核受体和肝酸盐 (HS) 蛋白质糖体进行代谢信号传递.
  • 作为FGF-FGFR复合体激活中的共受体,HS的精确分子机制尚不完全理解.

研究的目的:

  • 阐明HS在FGF23介导的信号传递中的核心受体功能的结构基础.
  • 确定FGFR受体二元化和激活的机制.

主要方法:

  • 电子显微镜 (cryo-EM) 解决FGF23-FGFR-αKlotho-HS四元复合物的结构.
  • 基于细胞的受体补充和异构化试验.

主要成果:

  • 对三种不同的FGF23-FGFR-αKlotho-HS复合体的结构确定显示出1:1:1的三元复合体,通过HS招募二次FGFR.
  • 一个单一的HS链促进了不对称的FGFR二分化和激活,这种机制也适用于膜FGF信号传递.
  • 发现αKlotho在二次受体招募或二元化中没有直接参与.

结论:

  • 这项研究推翻了对称的FGFR二元化模型,建立了由HS驱动的不对称机制.
  • 这些发现为开发针对代谢疾病和癌症的新疗法提供了结构基础.