在T细胞受体信号传导和免疫中对Tec激酶Rlk和Itk的要求
E M Schaeffer1, J Debnath, G Yap
1National Human Genome Research Institute, National Cancer Institute, National Institute for Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
概括
铁基酶,RLK和ITK,对于T细胞受体 (TCR) 信号传递至关重要. 它们的缺失会损害T细胞增殖,细胞因子生产和适应性免疫,突出显示它们在TCR信号转导中的作用.
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:
- 对于适应性免疫来说,T细胞受体 (TCR) 信号传递至关重要.
- 已知Zap-70和Src家族激酶的激活,但其他激素激酶的作用尚不清楚.
- 泰克家族的激酶涉及到各种信号通路.
研究的目的:
- 研究特基激酶,特别是RLK和ITK在TCR信号传递中的作用.
- 为了确定Rlk和Itk综合缺乏对TCR介导细胞反应的影响.
- 阐明TCR激活下游由Tec激酶调节的特定分子事件.
主要方法:
- 使用一种小鼠模型,对Rlk和Itk基因进行联合删除 (rlk-/-itk-/-).
- 评估了TCR诱导的T细胞增殖,细胞因子的产生,以及体外的亡.
- 在体内对Toxoplasma gondii感染的评估适应性免疫反应.
- 分析了TCR下游的早期分子事件,包括内醇三酸盐生产,调动和MAPK激活.
主要成果:
- 结合Rlk和Itk的删除导致TCR反应存在显著缺陷.
- 在实验室中观察到T细胞增殖,细胞因子产生和亡的损伤.
- 对Toxoplasma gondii的自适应性免疫反应在体内显著减少.
- 虽然最初的TCR信号事件完好无损,但中间信号通路受损,包括脂酶C-玛激活.
结论:
- 技术酶,RLK和ITK,是TCR信号的重要调节者.
- 这些激酶对于下游信号事件至关重要,包括调动和MAPK激活.
- 对于有效的T细胞激活和适应性免疫,RLK和ITK是不可或缺的.
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...
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...
TGF - β Signaling Pathway
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 are of three kinds RI, RII, and RIII. The RI...
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:
T Cell Types and Functions
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...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Cytotoxic T Cells-mediated Immune Response
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...


