拉特:ZAP-70氨酸激酶基质,它将T细胞受体与细胞激活联系起来
W Zhang1, J Sloan-Lancaster, J Kitchen
1Section on Lymphocyte Signaling, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430, USA.
Cell
|March 7, 1998
概括
研究人员发现了一种新型蛋白质,LAT (T细胞激活链接器),对T细胞受体信号传递至关重要. 通过特定的激酶对LAT的酸化招募其他分子,这对于T细胞激活至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 通过T细胞受体 (TCR) 介导的信号传递对适应性免疫至关重要.
- 在TCR路径中的关键信号组件仍然难以捉摸.
- 之前的研究已经确定了与Grb2,脂酶C-玛1和PI3K p85子单元相关的36-38 kDa蛋白.
研究的目的:
- 为了识别和描述一种参与TCR信号传递的新型蛋白质.
- 阐明这种蛋白在T细胞激活中的作用.
主要方法:
- 为36-38 kDa的蛋白质克隆cDNA.
- 氨基酸序列分析以预测蛋白质结构和功能.
- 在实验室中使用ZAP-70/Syk蛋白氨酸激酶进行酸化试验.
- 在T细胞中蛋白质的野生类型和突变形式的过度表达研究.
主要成果:
- 这种新型蛋白质是一种高度氨酸酸化的整体膜蛋白,具有多个酸化位.
- 通过ZAP-70/Syk的酸化导致下游信号分子的招募.
- 缺少关键氨酸残留物的突变LAT的过度表达抑制了T细胞的激活.
- 这种蛋白质被命名为LAT (T细胞激活链接器).
结论:
- LAT是TCR信号综合体的关键组成部分.
- LAT作为适应蛋白质起作用,调解T细胞激活必需的信号分子的招募.
- LAT代表了理解和潜在调节T细胞反应的关键目标.
相关概念视频
Enzyme-linked Receptors
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...
Enzyme-linked Receptors
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...
Amplifying Signals via Enzymatic Cascade
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 the...
Receptor Tyrosine Kinases
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...
MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Transducer Mechanism: Enzyme-Linked Receptors
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:


