马尔 (MyD88-adapter-like) 对于托尔类受体-4信号传导是必要的
K A Fitzgerald1, E M Palsson-McDermott, A G Bowie
1Department of Biochemistry, Trinity College, Dublin 2, Ireland.
Nature
|September 7, 2001
概括
一种新发现的蛋白质Mal (MyD88-adapter-like),在Toll-like受体-4 (TLR-4) 信号传输中起到关键的适配器作用. 马尔通过调解下游信号通路,促进了对格拉姆阴性细菌的先天免疫反应.
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:
- 天生的免疫依赖于托尔类受体 (TLRs) 来通过病原体相关的分子模式检测微生物病原体.
- TLR-4 特别识别了格拉姆阴性细菌中的脂多糖,从而启动了一个信号级联.
- MyD88是TLR信号传输中已知的适配蛋白,但TLR-4信号转导的完整机制尚不清楚.
研究的目的:
- 为了识别和描述参与托尔类受体-4 (TLR-4) 信号传输的新型适配蛋白.
- 阐明新发现的Mal (MyD88-adapter-like) 蛋白在TLR-4介导免疫反应中的作用.
主要方法:
- 人类基因组中的蛋白质识别和表征.
- 对NF-kappaB,Jun氨基终端激酶和细胞外信号调节激酶激活的分析.
- 对蛋白质与蛋白质相互作用的研究,包括用MyD88.8进行同质化和异质化.
- 主导负抑制试验评估Mal在TLR-4信号通路中的作用.
主要成果:
- 识别Mal,一个含有TIR域的细胞质蛋白质,作为人类基因组的新组成部分.
- 马尔激活了关键的信号分子,包括NF-kappaB,JNK和ERK1/2.2.
- 马尔与MyD88形成同质体和异质体,并证实其与TLR-4的关联.
- 马尔的NF-kappaB激活取决于IRAK-2,但不是IRAK,它特别介导TLR-4,但不是IL-1RI或IL-18R,信号传递.
结论:
- 马尔作为TLR-4信号传导中的关键适配蛋白.
- 马尔在对格拉姆阴性细菌成分 (如脂多糖) 的天生的免疫反应中发挥着特定的作用.
- 了解马尔的功能为TLR-4信号传递的分子机制提供了新的见解.
相关概念视频
Cell-surface Signaling
92.8K
Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
92.8K
Assembly of Signaling Complexes
4.7K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
4.7K
MAPK Signaling Cascades
7.3K
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...
7.3K
The JAK-STAT Signaling Pathway
10.2K
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...
10.2K
TGF - β Signaling Pathway
7.2K
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...
7.2K
Calmodulin-dependent Signaling
5.0K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.0K


