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Sorting nexin 16 regulates EGF receptor trafficking by phosphatidylinositol-3-phosphate interaction with the Phox domain

Title
Sorting nexin 16 regulates EGF receptor trafficking by phosphatidylinositol-3-phosphate interaction with the Phox domain
Authors
Choi, JHHong, WPKim, MJKim, JHRyu, SHSuh, PG
POSTECH Authors
Ryu, SH
Date Issued
Jan-2004
Publisher
COMPANY OF BIOLOGISTS LTD
Abstract
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.
Keywords
sorting nexin (SNX); epidermal growth factor (EGF); EGF receptor (EGFR); trafficking; phosphatidylinositol 3-phosphate (PtdIns(3)P); EPIDERMAL-GROWTH-FACTOR; SIGNAL-TRANSDUCTION; DOWN-REGULATION; SACCHAROMYCES-CEREVISIAE; MAP KINASE; ENDOCYTOSIS; DEGRADATION; ASSOCIATION; FAMILY; IDENTIFICATION
URI
http://oasis.postech.ac.kr/handle/2014.oak/17673
DOI
10.1242/JCS.01233
ISSN
0021-9533
Article Type
Article
Citation
JOURNAL OF CELL SCIENCE, vol. 117, no. 18, page. 4209 - 4218, 2004-01
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 RYU, SUNG HO
Dept of Life Sciences
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