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

Journal of Cell Science
Jang Hyun ChoiPann-Ghill Suh

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.

References

Nov 20, 1998·Molecular and Cellular Biology·Carol Renfrew HaftS I Taylor
Dec 10, 1999·The Journal of Biological Chemistry·O KranenburgW H Moolenaar
Nov 22, 2000·The Journal of Biological Chemistry·S A PhillipsCarol Renfrew Haft
Feb 13, 2001·Trends in Pharmacological Sciences·P TsaoMark von Zastrow
Mar 15, 2001·Current Opinion in Cell Biology·W E Miller, R J Lefkowitz
Jun 8, 2001·Traffic·P S McPhersonN K Hussain
Aug 11, 2001·Biochemical Society Transactions·Alexander Sorkin
May 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Qi ZhongGordon N Gill
Jun 1, 2002·Science·Lewis C Cantley
Jun 12, 2002·Molecular Biology of the Cell·Yingjie WangJoAnn Trejo
Jun 29, 2002·Cellular and Molecular Life Sciences : CMLS·A Toker
Aug 3, 2002·Nature Reviews. Molecular Cell Biology·Alexander Sorkin, Mark von Zastrow
Dec 4, 2002·Nature Reviews. Molecular Cell Biology·Carolyn A Worby, Jack E Dixon

Citations

Oct 1, 2008·Immunology and Cell Biology·Adam J MacNeil, Bill Pohajdak
Jun 14, 2005·Nature Cell Biology·Isabelle Le BlancJean Gruenberg
Oct 15, 2010·Molecular Biology of the Cell·Keisuke TabataTamotsu Yoshimori
Jan 21, 2010·Molecular and Cellular Biology·Hiroshi TakeuchiMasato Hirata
Jan 1, 2013·Cell Regeneration·Leilei ZhangDuanqing Pei
Jun 22, 2012·PloS One·Véronique PonsJean Gruenberg
Nov 28, 2013·International Journal of Molecular Medicine·Jianhua WuDongfang Wu
Apr 6, 2011·The Journal of Cell Biology·Avital A RodalJ Troy Littleton
Oct 3, 2009·The EMBO Journal·Ning Sheng LiuWanjin Hong
Feb 21, 2006·Biochemical and Biophysical Research Communications·Hao LiuYong-Jian Liu
Jan 25, 2008·The Biochemical Journal·Jonathan M Backer
Mar 17, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·José J FusterVicente Andrés
Jun 30, 2019·The Journal of Cell Biology·ShiYu WangAvital A Rodal

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