EPH-Ephrin 信号通路
中文名称
通路描述
在细胞发育过程中，细胞迁移和粘附是细胞形态发生的关键力量。细胞迁移到正确目的地的能力高度依赖于细胞膜上的信号传导。红细胞生成素产生的人肝细胞癌（EPH）受体及其配体，即 Ephrins（ Eph 受体相互作用蛋白，EFNs），负责精确控制以引导细胞到达其目的地。它们在发育胚胎的所有组织中表达，并参与多种发育过程，如轴突导向、心血管和骨骼发育以及组织模式化。此外，EPH 受体和 EFNs 也在神经系统中发育和成熟的突触中表达，在那里它们可能在调节突触可塑性和长时程增强中发挥作用。神经元中 EPHB 受体的激活诱导突触小体的快速形成和扩大，以及突触的快速成熟（Dalva 等，2007）。另一方面，EPHA4 的激活导致突触小体的消除（Murai 等，2003，Fu 等，2007）。EPH 受体是已知最大的受体酪氨酸激酶（RTK）家族，共有十四种受体，分为 A 亚类或 B 亚类：EPHA（1-8 和 10）和 EPHB（1-4 和 6）。EPH 受体具有重叠的功能，失去一种受体可以通过另一种具有相似表达模式和配体结合特异性的 EPH 受体部分补偿。EPH 受体具有一个 N 端胞外结构域，通过其与 Ephrin 配体的结合，一个短跨膜结构域，以及一个包含经典酪氨酸激酶催化结构域和其他蛋白质相互作用位点的胞内信号结构。Ephrins 也被分为 A 亚类（A1-A5），它们通过糖基磷脂酰肌醇（GPI）锚定到细胞膜上，以及 B 亚类（B1-B3），其中成员具有跨膜结构域和一段短、高度保守的胞内尾部，缺乏内源性催化活性。EPH 受体与其配体之间的相互作用需要细胞 - 细胞相互作用，因为两者都是膜结合的。EPH 受体和 EFNs 之间的紧密接触是信号传导所必需的。EPH/EFN 引发的信号传导是双向的，可以进入表达 EPH 或 EFN 的细胞或轴突。进入表达 EPH 受体的细胞称为“前向信号”，而进入表达 EFN 的细胞称为“反向信号”。（Dalva 等，2000，Grunwald 等，2004，Davy & Robbins 2000，Cowan 等，2004）
英文描述
EPH-Ephrin signaling During the development process cell migration and adhesion are the main forces involved in morphing the cells into critical anatomical structures. The ability of a cell to migrate to its correct destination depends heavily on signaling at the cell membrane. Erythropoietin producing hepatocellular carcinoma (EPH) receptors and their ligands, the ephrins (EPH receptors interacting proteins, EFNs), orchestrates the precise control necessary to guide a cell to its destination. They are expressed in all tissues of a developing embryo and are involved in multiple developmental processes such as axon guidance, cardiovascular and skeletal development and tissue patterning. In addition, EPH receptors and EFNs are expressed in developing and mature synapses in the nervous system, where they may have a role in regulating synaptic plasticity and long-term potentiation. Activation of EPHB receptors in neurons induces the rapid formation and enlargement of dendritic spines, as well as rapid synapse maturation (Dalva et al. 2007). On the other hand, EPHA4 activation leads to dendritic spine elimination (Murai et al. 2003, Fu et al. 2007).
EPH receptors are the largest known family of receptor tyrosine kinases (RTKs), with fourteen total receptors divided into either A- or B-subclasses: EPHA (1-8 and 10) and EPHB (1-4 and 6). EPH receptors can have overlapping functions, and loss of one receptor can be partially compensated for by another EPH receptor that has similar expression pattern and ligand-binding specificities. EPH receptors have an N-terminal extracellular domain through which they bind to ephrin ligands, a short transmembrane domain, and an intracellular cytoplasmic signaling structure containing a canonical tyrosine kinase catalytic domain as well as other protein interaction sites. Ephrins are also sub-divided into an A-subclass (A1-A5), which are tethered to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor, and a B-subclass (B1-B3), members of which have a transmembrane domain and a short, highly conserved cytoplasmic tail lacking endogenous catalytic activity. The interaction between EPH receptors and its ligands requires cell-cell interaction since both molecules are membrane-bound. Close contact between EPH receptors and EFNs is required for signaling to occur. EPH/EFN-initiated signaling occurs bi-directionally into either EPH- or EFN-expressing cells or axons. Signaling into the EPH receptor-expressing cell is referred as the forward signal and signaling into the EFN-expressing cell, the reverse signal. (Dalva et al. 2000, Grunwald et al. 2004, Davy & Robbins 2000, Cowan et al. 2004)
EPH receptors are the largest known family of receptor tyrosine kinases (RTKs), with fourteen total receptors divided into either A- or B-subclasses: EPHA (1-8 and 10) and EPHB (1-4 and 6). EPH receptors can have overlapping functions, and loss of one receptor can be partially compensated for by another EPH receptor that has similar expression pattern and ligand-binding specificities. EPH receptors have an N-terminal extracellular domain through which they bind to ephrin ligands, a short transmembrane domain, and an intracellular cytoplasmic signaling structure containing a canonical tyrosine kinase catalytic domain as well as other protein interaction sites. Ephrins are also sub-divided into an A-subclass (A1-A5), which are tethered to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor, and a B-subclass (B1-B3), members of which have a transmembrane domain and a short, highly conserved cytoplasmic tail lacking endogenous catalytic activity. The interaction between EPH receptors and its ligands requires cell-cell interaction since both molecules are membrane-bound. Close contact between EPH receptors and EFNs is required for signaling to occur. EPH/EFN-initiated signaling occurs bi-directionally into either EPH- or EFN-expressing cells or axons. Signaling into the EPH receptor-expressing cell is referred as the forward signal and signaling into the EFN-expressing cell, the reverse signal. (Dalva et al. 2000, Grunwald et al. 2004, Davy & Robbins 2000, Cowan et al. 2004)
所含基因
26 个基因