Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
Traffic. 2012 Apr;13(4):576-85. doi: 10.1111/j.1600-0854.2011.01322.x. Epub 2012 Jan 17.
The epidermal growth factor receptor (EGFR) is an important regulator of normal growth and differentiation, and it is involved in the pathogenesis of many cancers. Endocytic downregulation is central in terminating EGFR signaling after ligand stimulation. It has been shown that p38 MAPK activation also can induce EGFR endocytosis. This endocytosis lacks many of the characteristics of ligand-induced EGFR endocytosis. We compared the two types of endocytosis with regard to the requirements for proteins in the internalization machinery. Both types of endocytosis require clathrin, but while epidermal growth factor (EGF)-induced EGFR internalization also required Grb2, p38 MAPK-induced internalization did not. Interestingly, AP-2 knock down blocked p38 MAPK-induced EGFR internalization, but only mildly affected EGF-induced internalization. In line with this, simultaneously mutating two AP-2 interaction sites in EGFR affected p38 MAPK-induced internalization much more than EGF-induced EGFR internalization. Thus, it seems that EGFR in the two situations uses different sets of internalization mechanisms.
表皮生长因子受体（EGFR）是正常生长和分化的重要调节因子，它参与了许多癌症的发病机制。内吞作用的下调是配体刺激后终止 EGFR 信号的关键。已经表明，p38 MAPK 的激活也可以诱导 EGFR 的内吞作用。这种内吞作用缺乏配体诱导的 EGFR 内吞作用的许多特征。我们比较了这两种内吞作用在摄取机制中的蛋白质要求。两种内吞作用都需要网格蛋白，但表皮生长因子（EGF）诱导的 EGFR 内吞作用还需要 Grb2，而 p38 MAPK 诱导的内吞作用则不需要。有趣的是，AP-2 敲低阻断了 p38 MAPK 诱导的 EGFR 内吞作用，但对 EGF 诱导的内吞作用的影响较小。与此一致的是，同时突变 EGFR 中的两个 AP-2 相互作用位点对 p38 MAPK 诱导的内吞作用的影响远大于 EGF 诱导的 EGFR 内吞作用。因此，似乎 EGFR 在这两种情况下使用不同的内吞作用机制。
