细胞因子通过非受体蛋白铁氨酸激酶信号传递
1Department of Immunology, Faculty of Medicine, University of Tokyo, Japan.
Science (New York, N.Y.)
|April 14, 1995
概括
细胞因子通过缺乏内在激酶域的受体调解细胞通信. 这些受体激活非受体蛋白氨酸激酶 (PTKs),影响细胞反应和细胞因子活性.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子信号传输的方法
背景情况:
- 细胞因子是细胞间通信的关键可溶媒体,包括介质蛋白,干扰素和殖民地刺激因子.
- 细胞因子的关键特征包括功能冗余和性,这意味着它们可以产生多种效应,不同的细胞因子可以引起类似的反应.
- 大多数细胞因子受体缺乏内在的蛋白质氨酸激酶 (PTK) 域,这就提出了关于受体刺激如何导致细胞内氨酸酸化的问题.
研究的目的:
- 阐明细胞因子受体刺激导致细胞内蛋白质氨酸酸化的机制.
- 了解非受体蛋白氨酸激酶 (PTKs) 在细胞因子信号通路中的作用.
- 探索细胞因子受体的细胞体内结构如何促进下游信号传输.
主要方法:
- 摘要没有指定方法,但暗示分析细胞因子受体结构和相关的信号分子.
- 专注于细胞因子受体和细胞内蛋白氨酸激酶 (PTKs) 之间的相互作用.
主要成果:
- 细胞因子受体刺激触发了细胞内蛋白质的快速氨酸酸化,包括受体本身.
- 细胞因子受体招募或激活各种非受体PTK,以启动下游信号传输.
- 细胞因子受体的细胞体内结构使不同PTK家族的协调作用成为可能.
结论:
- 细胞因子受体缺乏内在的PTK域,但有效地利用非受体PTK进行信号转导.
- 细胞因子受体对PTK的招募和激活对于细胞反应至关重要.
- 细胞因子受体的进化的细胞体内结构允许通过多种PTK相互作用对细胞因子活性进行细胞类型特定的调节.
更多相关视频
相关概念视频
01:15Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:22Amplifying 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...
01:26Receptor 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...
01:07MAPK 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...
01:20The JAK-STAT Signaling Pathway
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...