Davy A, Robbins S M
Departments of Oncology and Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada.
EMBO J. 2000 Oct 16;19(20):5396-405. doi: 10.1093/emboj/19.20.5396.
The ephrins are membrane-tethered ligands for the Eph receptor tyrosine kinases, which play important roles in patterning of the nervous and vascular systems. It is now clear that ephrins are more than just ligands and can also act as signalling-competent receptors, participating in bidirectional signalling. We have recently shown that ephrin-A5 signals within caveola-like domains of the plasma membrane upon engagement with its cognate Eph receptor, leading to increased adhesion of the cells to fibronectin. Here we show that ephrin-A5 controls sequential biological events that are consistent with its role in neuronal guidance. Activation of ephrin-A5 induces an initial change in cell adhesion followed by changes in cell morphology. Both effects are dependent on the activation of beta1 integrin involving members of the Src family of protein tyrosine kinases. The prolonged activation of ERK-1 and ERK-2 is required for the change in cell morphology. Our work suggests a new role for class A ephrins in specifying the affinity of the cells towards various extracellular substrates by regulating integrin function.
Ephrin是Eph受体酪氨酸激酶的膜结合配体，在神经和血管系统的模式形成中发挥重要作用。现在很清楚，ephrin不仅仅是配体，还可以作为具有信号传导能力的受体，参与双向信号传导。我们最近发现，ephrin-A5与其同源Eph受体结合后，在质膜的小窝样结构域内发出信号，导致细胞与纤连蛋白的粘附增加。在这里，我们表明ephrin-A5控制着与其在神经元导向中的作用相一致的一系列生物学事件。ephrin-A5的激活诱导细胞粘附的初始变化，随后是细胞形态的变化。这两种效应都依赖于涉及蛋白酪氨酸激酶Src家族成员的β1整合素的激活。细胞形态的变化需要ERK-1和ERK-2的长期激活。我们的工作表明，A类ephrin通过调节整合素功能，在确定细胞对各种细胞外基质的亲和力方面具有新的作用。
