Employment of the epidermal growth factor receptor in growth factor-independent signaling pathways.
Employment of the epidermal growth factor receptor in growth factor-independent signaling pathways.
复制标题
表皮生长因子受体在非生长因子独立的信号传导途径中的使用。
DOI：
10.1083/jcb.146.4.697
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发表时间：
1999-08-23
影响因子：
7.8
通讯作者：
Carpenter, G
中科院分区：
文献类型：
--
作者：
Carpenter, G
生长因子受体和激素受体的传统观点一般认为，特异性配体直接识别其同源受体上的高度选择性结合位点，从而激活受体依赖性信号传导和生物反应。在EGF受体的情况下，几种结构相关的蛋白质（EGF、转化生长因子α、双调蛋白、β细胞素、表皮调节蛋白、肝素结合EGF）被认为是直接激动剂。这些生长因子中的每一种都与EGF受体的胞外域结合，并通过涉及二聚化、受体酪氨酸激酶胞质结构域的活化和受体的自磷酸化的机制引起其活化。这一过程启动了导致有丝分裂的信号通路。最近已经很明显，EGF受体也是信号网络的一部分，由不直接与该受体相互作用的刺激激活。这些刺激包括特异性结合其他膜受体的激动剂、膜去极化剂和环境应激物。这些数据不仅显示了EGF受体的EGF非依赖性酪氨酸磷酸化，而且还提供了实验证据，表明EGF受体参与了由这些不同刺激引发的信号传导事件和细胞反应。总的来说，这些结果意味着在没有直接激动剂的情况下，EGF受体被用于广泛的生物信号传导过程。本文的目的是审查和评估这些非经典的EGF受体的用途。
THE traditional view of growth factor receptors and hormone receptors in general is that a specific ligand directly recognizes a highly selective binding site on its cognate receptor and, thereby, activates receptor-dependent signaling and biological responses. In the case of the EGF receptor, several structurally related proteins (EGF, transforming growth factor alpha, amphiregulin, betacellulin, epiregulin, heparin-binding EGF) are recognized as direct agonists. Each of these growth factors binds to the ectodomain of the EGF receptor and provokes its activation through a mechanism that involves dimerization, activation of the receptor tyrosine kinase cytosolic domain, and autophosphorylation of the receptor. This process initiates signaling pathways that lead to mitogenesis.Recently it has become apparent that the EGF receptor is also part of signaling networks activated by stimuli that do not directly interact with this receptor. These stimuli include agonists that specifically bind to other membrane receptors, membrane depolarization agents, and environmental stressors. The data not only show EGF-independent tyrosine phosphorylation of the EGF receptor, but also provide experimental evidence that the EGF receptor participates in the signaling events and cellular responses initiated by these various stimuli. Collectively, the results imply that in the absence of direct agonists the EGF receptor is employed in a wide array of biological signaling processes. The purpose of this article is to review and evaluate these nonclassical uses of the EGF receptor.