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相关概念视频

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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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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Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
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Activation of Integrins01:15

Activation of Integrins

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Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
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Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

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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.
Some...
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T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
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相关实验视频

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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-&#946; Signaling
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潜伏的TGF-β结构和激活

Minlong Shi1, Jianghai Zhu, Rui Wang

  • 1Immune Disease Institute, Children's Hospital Boston and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Nature
|June 17, 2011
PubMed
概括

转化生长因子-β (TGF-β) 激活涉及整合素结合和力. 结构分析揭示了产域如何屏蔽TGF-β,需要机械力释放生长因子.

科学领域:

  • 生物化学 生物化学
  • 结构生物学 结构生物学
  • 细胞生物学 细胞生物学

背景情况:

  • 转化生长因子-β (TGF-β) 对于细胞生长和恒温至关重要.
  • TGF-β被存储在细胞外基质中,作为一个潜在的复合体与其原域.
  • 激活需要整合素结合和机械力.

研究的目的:

  • 阐明潜伏TGF-β复合体形成和激活的结构基础.
  • 了解产域在调节TGF-β可用性的作用.

主要方法:

  • 二维猪 proTGF-β1.1.的X射线晶体学
  • 分析蛋白质结构和相互作用.

主要成果:

  • 揭示了一种新的环形原域折叠,可以屏蔽生长因子.
  • 证明单独结合整合素不足以释放TGF-β.
  • 确定了一种依赖力量的机制,包括解开产域"束衣".

结论:

  • 产域的结构是调节TGF-β活性的关键.
  • 取决于力量的激活对于释放活跃的TGF-β至关重要.

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  • 对TGF-β调节的洞察力对发育和疾病有影响.