人类pannexin 1通道在Tyr199和Tyr309中没有被Src氨酸激酶酸化
Zheng Ruan1, Junuk Lee1, Yangyang Li1
1Department of Structural Biology, Van Andel Institute, Grand Rapids, United States.
eLife
|May 23, 2024
概括
商业上可获得的Pannexin 1 (PANX1) 酸化抗体是非特异性的. 需要重新检查PANX1通道的氨酸酸化依赖激活.
科学领域:
- 分子生物学分子生物学
- 蜂信号传输是如何进行的
- 离子通道功能 离子通道功能
背景情况:
- 蛋白质酸化调节蛋白质的活性和功能.
- 泛素1 (PANX1) 通道与细胞死亡,炎症和肌肉收缩有关.
- 建议通过 Src 激酶介导的 PANX1 铁酸化来激活该通道.
研究的目的:
- 为了验证特定的氨酸酸化位在PANX1通道激活中的作用.
- 评估用于检测PANX1酸化的抗体的特异性.
- 重新评估目前的Src-依赖的PANX1通道激活模型.
主要方法:
- 测试商业抗体对酸化PANX1 Tyr198/Tyr308 (老鼠) 的特异性.
- 在异质表达系统中研究PANX1的Src酶酸化.
- 使用经过验证的方法分析内源性PANX1酸化.
主要成果:
- 针对 PANX1 酸化位点的商业抗体 Tyr198/Tyr308 是非特异性的.
- 在测试系统中,Tyr198和Tyr308都不是Src激酶的主要酸化部位.
- 关于PANX1酸化的现有数据可能需要重新解释.
结论:
- 通常用于PANX1酸化的抗体的特异性是可疑的.
- 通过Tyr198/308酸化对Src依赖的PANX1激活的拟议机制需要重新评估.
- 需要进一步的研究来阐明PANX1通道调节.
相关概念视频
Receptor Tyrosine Kinases
12.7K
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...
12.7K
The JAK-STAT Signaling Pathway
8.8K
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...
8.8K
Enzyme-linked Receptors
78.2K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
78.2K
PI3K/mTOR/AKT Signaling Pathway
3.5K
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...
3.5K
Transducer Mechanism: Enzyme-Linked Receptors
2.4K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.4K
Tension Response at Adherens Junctions
2.6K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.6K


