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相关概念视频

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...

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相关实验视频

Updated: May 7, 2026

Accurate and Simple Measurement of the Pro-inflammatory Cytokine IL-1β using a Whole Blood Stimulation Assay
06:29

Accurate and Simple Measurement of the Pro-inflammatory Cytokine IL-1β using a Whole Blood Stimulation Assay

Published on: March 2, 2011

促炎性刺激会诱导IKKalpha介导的PIAS1酸化,以限制炎症和免疫力.

Bin Liu1, Yonghui Yang, Vasili Chernishof

  • 1Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.

Cell
|June 2, 2007
PubMed
概括

炎症信号激活IKKalpha以化PIAS1,这是一个通过阻断基因激活来抑制炎症的关键调节器. 这种酸化对于PIAS1是必不可少的.

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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

相关实验视频

Last Updated: May 7, 2026

Accurate and Simple Measurement of the Pro-inflammatory Cytokine IL-1β using a Whole Blood Stimulation Assay
06:29

Accurate and Simple Measurement of the Pro-inflammatory Cytokine IL-1β using a Whole Blood Stimulation Assay

Published on: March 2, 2011

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

科学领域:

  • 免疫学 免疫学 免疫学
  • 分子生物学分子生物学
  • 转录条例 转录条例 转录条例

背景情况:

  • 炎症刺激向核发出信号以限制炎症的机制尚未完全理解.
  • 激活STAT1的蛋白抑制剂 (PIAS1) 是一种转录调节剂,具有小的泛素相关修饰剂 (SUMO) E3结合酶活性,通过阻断NF-kappaB和STAT1与基因促进体结合来抑制免疫反应.

研究的目的:

  • 阐明炎症刺激导致核抑制炎症的信号通路.
  • 研究PIAS1酸化在调节炎性基因激活中的作用.

主要方法:

  • 利用突变研究来评估PIAS1酸化在Ser90.0的功能.
  • 采用了TNF治疗,并分析了野生类型和突变PIAS1与基因促进者的关联.
  • 研究了IKKalpha,IKKbeta和PIAS1.1之间的体内相互作用.

主要成果:

  • 在响应炎症刺激时,PIAS1在Ser90上快速酸化.
  • 化Ser90对PIAS1的转录抑制活动至关重要.
  • 野生类型的PIAS1,但不是Ser90A突变,在TNF治疗时与NF-kappaB向基因促进体结合.
  • IKKalpha,而不是IKKbeta,与PIAS1相互作用,并调解Ser90酸化,这取决于PIAS1的SUMO结合酶活性.

结论:

  • 确定了一个信号通路,炎症刺激激活IKKalpha.
  • IKKalpha 在Ser90.0 处调解PIAS1的化,而这种化依赖于sumoylation.
  • 这一过程导致PIAS1.1立即抑制炎症基因激活.