Kuijper Sanne, Turner Christopher J, Adams Ralf H
Vascular Development Laboratory, Cancer Research UK, London Research Institute, London, UK.
Trends Cardiovasc Med. 2007 Jul;17(5):145-51. doi: 10.1016/j.tcm.2007.03.003.
The large families of Eph receptor tyrosine kinases and their ephrin ligands transduce signals in a cell-cell contact-dependent fashion and thereby coordinate the growth, differentiation, and patterning of almost every organ and tissue. Eph-ephrin interactions can trigger a wide array of cellular responses, including cell adhesion, boundary formation, and repulsion. The exact mechanisms leading to this diversity of responses are unclear but appear to involve differential signaling, proteolytic cleavage of ephrins, and endocytosis of the ligand-receptor complex. In the developing cardiovascular system, Eph and ephrin molecules control the angiogenic remodeling of blood vessels and lymphatic vessels and play essential roles in endothelial cells as well as in supporting pericytes and vascular smooth muscle cells. Recent evidence suggests that Ephs and ephrins may also be involved in pathological angiogenesis, in particular, the neovascularization of tumors. Consequently, the expression, interactions, or signaling of Eph-ephrin molecules might be targets for future therapeutic approaches.
Eph受体酪氨酸激酶大家族及其ephrin配体以细胞间接触依赖的方式转导信号，从而协调几乎每个器官和组织的生长、分化和模式形成。Eph-ephrin相互作用可引发一系列细胞反应，包括细胞黏附、边界形成和排斥。导致这种反应多样性的确切机制尚不清楚，但似乎涉及差异信号传导、ephrin的蛋白水解切割以及配体-受体复合物的内吞作用。在发育中的心血管系统中，Eph和ephrin分子控制血管和淋巴管的血管生成重塑，并在内皮细胞以及支持周细胞和血管平滑肌细胞中发挥重要作用。最近的证据表明，Eph和ephrin也可能参与病理性血管生成，特别是肿瘤的新生血管形成。因此，Eph-ephrin分子的表达、相互作用或信号传导可能成为未来治疗方法的靶点。
