Regulation of endocytosis, nuclear translocation, and signaling of fibroblast growth factor receptor 1 by E-cadherin
Regulation of endocytosis, nuclear translocation, and signaling of fibroblast growth factor receptor 1 by E-cadherin
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DOI：
10.1091/mbc.e04-09-0845
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发表时间：
2005-01-01
影响因子：
3.3
通讯作者：
Stow, JL
中科院分区：
文献类型：
--
作者：
Bryant, DM;Wylie, FG;Stow, JL
成纤维细胞生长因子（FGF）受体（FGFR）信号调节多种细胞功能，包括上皮细胞形态发生。在上皮细胞中，E-cadherin在细胞-细胞粘附中起关键作用，其功能可通过内吞运输来调节。在这项研究中，我们研究了FGFR 1和E-钙粘蛋白的位置、运输和功能，并报告了一种基于内吞运输的新机制，用于E-钙粘蛋白和FGFR 1信号的共调节。FGF诱导表面FGFR 1和表面E-钙粘蛋白的内化，随后是FGFR 1的核转位。这两种蛋白质的内化受共同的内吞机制调节，导致FGFR 1和E-钙粘蛋白共同内化到早期内体中。通过阻断内吞作用，我们发现这是FGFR 1核转位的必要的初始步骤。E-cadherin的过表达阻断E-cadherin和FGFR 1的共内吞作用、FGFR 1的核转位和FGF诱导的信号传导至丝裂原活化蛋白激酶途径。此外，通过过表达p120（ctn）稳定表面粘附性E-钙粘蛋白，也阻断了FGFR 1的内化和核转位。这些数据表明，联合内吞和贩运是一种新的机制，在细胞信号转导和形态发生过程中的E-cadherin和FGFR 1的共调节。
Fibroblast growth factor (FGF) receptors (FGFRs) signal to modulate diverse cellular functions, including epithelial cell morphogenesis. In epithelial cells, E-cadherin plays a key role in cell-cell adhesion, and its function can be regulated through endocytic trafficking. In this study, we investigated the location, trafficking, and function of FGFR1 and E-cadherin and report a novel mechanism, based on endocytic trafficking, for the coregulation of E-cadherin and signaling from FGFR1. FGF induces the internalization of surface FGFR1 and surface E-cadherin, followed by nuclear translocation of FGFR1. The internalization of both proteins is regulated by common endocytic machinery, resulting in cointernalization of FGFR1 and E-cadherin into early endosomes. By blocking endocytosis, we show that this is a requisite, initial step for the nuclear translocation of FGFR1. Overexpression of E-cadherin blocks both the coendocytosis of E-cadherin and FGFR1, the nuclear translocation of FGFR1 and FGF-induced signaling to the mitogen-activated protein kinase pathway. Furthermore, stabilization of surface adhesive E-cadherin, by overexpressing p120(ctn), also blocks internalization and nuclear translocation of FGFR1. These data reveal that conjoint endocytosis and trafficking is a novel mechanism for the coregulation of E-cadherin and FGFR1 during cell signaling and morphogenesis.