Sorting nexin 16 regulates EGF receptor trafficking by phosphatidylinositol-3-phosphate interaction with the Phox domain
Sorting nexin 16 regulates EGF receptor trafficking by phosphatidylinositol-3-phosphate interaction with the Phox domain
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DOI：
10.1242/jcs.01233
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发表时间：
2004-08-15
影响因子：
4
通讯作者：
Suh, PG
中科院分区：
文献类型：
--
作者：
Choi, JH;Hong, WP;Suh, PG
含有Phox （PX）结构域的分类连接蛋白（SNXs）参与上皮生长因子受体（EGFR）的膜运输和分类过程的调节。在这项研究中，我们研究了SNX16是否通过调节EGFR运输来调节egf诱导的细胞信号传导。SNX16通过其PX结构域定位于早期和再循环核内体。PX结构域的突变破坏了SNX16与磷脂酰肌醇3-磷酸之间的关联[PtdIns(3)P]。用wortmannin（一种PtdIns 3-激酶抑制剂）治疗可以消除SNX16的内体定位，这表明SNX16的细胞内定位受PtdIns 3-激酶活性的调节。在COS-7细胞中，经EGF刺激后发现SNX16与EGFR相关。此外，SNX16的过表达增加了egf诱导的EGFR降解速率，抑制了egf诱导的ERK和血清反应因子（SRE）的上调。此外，PX结构域突变显著阻断了SNX16对egf诱导的ERK和SRE活化的抑制作用。根据这些结果，我们认为SNX16引导EGFR的分选到内体室，从而调节egf诱导的细胞信号传导。
Sorting nexins (SNXs) containing the Phox (PX) domain are implicated in the regulation of membrane trafficking and sorting processes of epithelial growth factor receptor (EGFR). In this study, we investigated whether SNX16 regulates EGF-induced cell signaling by regulating EGFR trafficking. SNX16 is localized in early and recycling endosomes via its PX domain. Mutation of the PX domain disrupted the association between SNX16 and phosphatidylinositol 3-phosphate [PtdIns(3)P]. Treatment with wortmannin, a PtdIns 3-kinase inhibitor, abolished the endosomal localization of SNX16, suggesting that the intracellular localization of SNX16 is regulated by PtdIns 3-kinase activity. SNX16 was found to associate with EGFR after stimulation with EGF in COS-7 cells. Moreover, overexpression of SNX16 increased the rate of EGF-induced EGFR degradation and inhibited the EGF-induced up-regulation of ERK and serum response element (SRE). In addition, mutation in the PX domain significantly blocked the inhibitory effect of SNX16 on EGF-induced activation of ERK and SRE. From these results, we suggest that SNX16 directs the sorting of EGFR to the endosomal compartment and thus regulates EGF-induced cell signaling.