通过STAT3-Smad1复合体在胎儿大脑中的协同信号传递,由p300桥接
K Nakashima1, M Yanagisawa, H Arakawa
1Department of Molecular Cell Biology, Cell Fate Modulation Research Unit, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
Science (New York, N.Y.)
|April 16, 1999
概括
白血病抑制因子 (LIF) 和骨形态遗传蛋白-2 (BMP2) 协同作用,诱导神经前代细胞进入星球细胞. 这一过程涉及联合激活器p300桥接STAT3和Smad1,促进合作信号.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 白血病抑制因子 (LIF) 和骨形态遗传蛋白-2 (BMP2) 是参与细胞分化的关键细胞因子.
- 这些细胞因子利用不同的受体和细胞内信号通路,分别涉及STAT和Smad.
- 神经前代细胞分化为星球细胞,这是大脑发育和修复的关键过程.
研究的目的:
- 研究LIF和BMP2在诱导神经前细胞的星球细胞分化中的协同机制.
- 阐明转录协同激活剂p300在LIF和BMP2通路之间的合作信号中介作用.
主要方法:
- 主要的胎儿神经前体细胞被用LIF和BMP2.2治疗.
- 共同免疫沉试验被用来检测p300,STAT3和Smad1.1.之间的蛋白质与蛋白质相互作用.
- 用西式涂抹和定量PCR分析基因表达和蛋白质水平.
主要成果:
- LIF和BMP2表现出协同效应,促进神经前代细胞分化为星球细胞.
- 转录协同激活器p300与STAT3和Smad1.1进行物理相互作用.
- p300与STAT3和Smad1形成了一个复合体,以细胞因子依赖的方式将这两个信号通路连接起来.
结论:
- 在天体细胞诱导中,LIF和BMP2的合作信号由STAT3-p300-Smad1复合体的形成介导.
- 这种分子复合体集成了来自两种细胞因子的信号,从而使神经原始细胞有效地分化为星球细胞.
- 了解这种途径为神经发育提供了洞察力,并为神经疾病提供了潜在的治疗策略.
相关概念视频
02:33Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
01:30Assembly of Signaling Complexes
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,...
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...
01:20The 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...
01:16TGF - 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...