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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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関連する実験動画

Updated: May 1, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-&#946; Signaling
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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

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潜伏TGF-β構造と活性化について

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
まとめ

変形成長因子β (TGF-β) の活性化には,インテグリン結合と力がある. 構造分析により,プロドメインがTGF-βをどのように遮断し,成長因子を放出するには機械的な力が必要です.

科学分野:

  • バイオケミストリー バイオケミストリー
  • 構造生物学 構造生物学とは
  • 細胞生物学 細胞生物学

背景:

  • 変形成長因子β (TGF-β) は,細胞の成長とホメオスタシスに不可欠です.
  • TGF-βは細胞外マトリックスに潜伏複合体としてプロドメインで保存されます.
  • アクティベーションには,インテグリン結合と機械的な力が必要です.

研究 の 目的:

  • 潜伏のTGF-β複合体の形成と活性化の構造的基礎を解明する.
  • TGF-βの可用性を調節するプロドメインの役割を理解する.

主な方法:

  • 二次元豚 proTGF-β1.1.のX線結晶学
  • タンパク質の構造と相互作用の分析.

主要な成果:

  • 成長因子を遮断する新しい環状プロドメインの折りたたみを明らかにした.
  • インテグリン結合だけではTGF-βの放出には不十分であることが示された.
  • プロドメイン"ストレートジャケット"の解錠を含む力に依存するメカニズムを特定しました.

結論:

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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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Visualization and Quantification of TGF&#946;/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
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Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

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  • プロドメインの構造は,TGF-βの活性を調節する鍵です.
  • 活性TGF-βの放出には,力に依存した活性化が不可欠である.
  • TGF-βの調節に関する洞察は,発達と疾患に影響を及ぼします.