Kim Hong Joo, Taylor Laura J, Bar-Sagi Dafna
Graduate Program in Molecular and Cellular Biology, State University of New York at Stony Brook, Stony Brook, NY 11794-5222, USA.
Curr Biol. 2007 Mar 6;17(5):455-61. doi: 10.1016/j.cub.2007.01.059. Epub 2007 Feb 22.
Ligand-induced activation of the epidermal growth factor receptor (EGFR) initiates multiple signal-transduction pathways as well as trafficking events that relocalize the receptors from the cell surface to intracellular endocytic compartments. Although there is growing awareness that endocytic transport can play a direct role in signal specification, relatively little is known about the molecular mechanisms underlying this link. Here we show that human Sprouty 2 (hSpry2), a protein that has been implicated in the negative regulation of receptor tyrosine kinase (RTK) signaling [1], interferes with the trafficking of activated EGFR specifically at the step of progression from early to late endosomes. This effect is mediated by the binding of hSpry2 to the endocytic regulatory protein, hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), and leads to a block in intracellular signal propagation. These observations suggest that EGFR signaling is controlled by a novel mechanism involving trafficking-dependent alterations in receptor compartmentalization.
配体诱导的表皮生长因子受体（EGFR）激活引发多种信号转导途径以及运输事件，这些事件会使受体从细胞表面重新定位到细胞内吞小室。尽管人们越来越意识到内吞运输可能在信号特异性中发挥直接作用，但对于这种联系背后的分子机制却知之甚少。在这里，我们表明人类Sprouty 2（hSpry2），一种与受体酪氨酸激酶（RTK）信号的负调控有关的蛋白质[1]，在从早期内体到晚期内体的进展步骤中特异性地干扰活化的EGFR的运输。这种效应是由hSpry2与内吞调节蛋白，肝细胞生长因子调节的酪氨酸激酶底物（Hrs）的结合介导的，并导致细胞内信号传播受阻。这些观察结果表明，EGFR信号传导受一种新机制控制，该机制涉及受体区室化中依赖运输的改变。
