Pyk2 and FAK regulate neurite outgrowth induced by growth factors and integrins
Pyk2 and FAK regulate neurite outgrowth induced by growth factors and integrins
复制标题
DOI：
10.1038/35023515
复制
发表时间：
2000-09-01
影响因子：
21.3
通讯作者：
Dikic, I
中科院分区：
文献类型：
--
作者：
Ivankovic-Dikic, I;Grönroos, E;Dikic, I
由受体酪氨酸激酶和整合素启动的信号通路的整合对于生长因子介导的生物反应是必不可少的。在这里，我们发现，生长因子受体和整合素的共同刺激激活了粘着斑激酶(FAK)家族，促进了PC12和SH-SY5Y细胞中神经突起的生长。PYK2和FAK通过其羧基和氨基末端结构域与含有表皮生长因子(EGF)受体的粘附型复合体结合。PYK2或FAK的C末端区域的表达足以阻止轴突生长，但不能阻止细胞外信号调节激酶(ERK)的激活。此外，Pyk2/FAK的激活和自动磷酸化，以及它们的黏附靶向结构域的效应物，如paxlin，对于控制轴突形成的信号的传播是重要的。因此，Pyk2/FAK在神经元整合素/生长因子受体复合体附近的信号整合中具有重要作用。
Integration of signalling pathways initiated by receptor tyrosine kinases and integrins is essential for growth-factor-mediated biological responses. Here we show that co-stimulation of growth-factor receptors and integrins activates the focal-adhesion kinase (FAK) family to promote outgrowth of neurites in PC12 and SH-SY5Y cells. Pyk2 and FAK associate with adhesion-based complexes that contain epidermal growth factor (EGF) receptors, through their carboxy- and amino-terminal domains. Expression of the C-terminal domain of Pyk2 or of FAK is sufficient to block neurite outgrowth, but not activation of extracellular-signal-regulated kinase (ERK). Moreover, activation and autophosphorylation of Pyk2/FAK, as well as of effecters of their adhesion-targeting domains, such as paxillin, ave important for propagation of signals that control neurite formation. Thus, Pyk2/FAK have important functions in signal integration proximal to integrin/growth-factor receptor complexes in neurons.