准备打击:蛇形受体对血栓素A2的信号传递中的急性事件
1Division of Cardiovascular Medicine, Lankenau Institute for Medical Research, Rm 128, 100 E Lancaster Ave, Wynnewood, PA 19096, USA; Division of Perinatal Research, Kolling Institute of Medical Research, Faculty of Medicine and Health, University of Sydney, St Leonards, NSW 2065, Australia.
Pharmacology & therapeutics
|June 15, 2023
概括
血红素A2 (TP) 信号传递,曾经仅限于血小板激活,现在影响许多疾病. 最近的发现揭示了超越G蛋白合的复杂信号通路,突出了TP受体.
科学领域:
- 生物化学和分子生物学
- 生理学 生理学 生理学
- 免疫学 免疫学 免疫学
背景情况:
- 血栓素A2 (TP) 信号已经从血小板激活剂演变为各种生理和病理过程中的关键参与者.
- TP信号与主要疾病的发病有关,包括癌症,动脉样硬化,心血管疾病,喘和寄生虫感染.
- 两种TP受体异型,TPα和TPβ,通过替代拼接从TBXA2R基因产生,调解不同的细胞反应.
研究的目的:
- 审查了解TP受体信号传导机制的最新进展.
- 探索G蛋白合和TP受体的翻译后修改的结构基础.
- 要突出涉及TP受体及其相互作用蛋白的非G蛋白合信号通路的新兴领域.
主要方法:
- 关于氨酸A2受体信号传导的最近研究的文献综述.
- 对阐明G蛋白合机制和受体翻译后修改的研究进行分析.
- 检查识别TP受体相互作用蛋白和非G蛋白结合通路的研究.
主要成果:
- 已经建立了对TP受体G蛋白合的结构洞察.
- 翻译后的修改显著调节TP受体信号传递.
- 已经确定了70多种相互作用的蛋白质,揭示TP受体是G蛋白激活之外的多种信号通路的关联点.
结论:
- TP信号是一个复杂的网络,其作用远远超出了最初的描述.
- 最近的发现正在彻底改变对TP受体信号传播的理解.
- TP信号领域正在迅速发展,揭示了新的治疗点和对疾病机制的洞察力.
相关概念视频
Intracellular Signaling Affects Focal Adhesions
2.7K
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...
Some...
2.7K
Formation of the Platelet Plug
6.7K
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
6.7K
Amplifying Signals via Enzymatic Cascade
8.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.5K
Vascular Spasm
1.5K
The vascular phase, also known as vasospasm, is the initial stage of hemostasis, crucial for preventing excessive bleeding when a blood vessel is injured. After a vessel is cut, nerves in the damaged area trigger pain and other sensory impulses. Simultaneously, the smooth muscles in the vessel wall contract, resulting in a vascular spasm. This contraction reduces the vessel's diameter at the injury site, slowing or stopping blood loss through the vessel wall. Vascular spasms typically last...
1.5K
Intracellular Signaling Cascades
47.1K
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
47.1K
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
204
Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
204


