Inhibitory regulation of EGF receptor degradation by sorting nexin 5

Hao Liu, Zu Qiang Liu, Carol X.Q. Chen, Stephen Magill, Yu Jiang, Yong Jian Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Endosomal trafficking of EGF receptor (EGFR) upon stimulation is a highly regulated process during receptor-mediated signaling. Recently, the sorting nexin (SNX) family has emerged as an important regulator in the membrane trafficking of EGFR. Here, we report the identification of a novel interaction between two members of the family, SNX1 and SNX5, which is mediated by the newly defined BAR domain of both SNXs. We have also shown that the PX domain of SNX5 binds specifically to PtdIns other than to PtdIns(3)P. Furthermore, the BAR domain but not the PX domain of SNX5 is sufficient for its subcellular membrane association. Functionally, overexpression of SNX5 inhibits the degradation of EGFR. This process appears to be independent of its interaction with SNX1. However, overexpression of SNX1 is able to attenuate the effect of SNX5 on EGFR degradation, suggesting the two proteins may play antagonistic roles in regulating endosomal trafficking of the receptor.

Original languageEnglish (US)
Pages (from-to)537-546
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume342
Issue number2
DOIs
StatePublished - Apr 7 2006
Externally publishedYes

Funding

We gratefully acknowledge Dr. Alan H. Wells at the University of Pittsburgh for providing NR6/EGFR cell lines. We thank Drs. Linton Traub and Sanjay Mishra for generous help in the establishment of liposomal binding assay in the laboratory. This work was supported by Grants from the National Institutes of Health (MH62092-01A1 to Y.L. and GM068832-01A2 to Y.J.), the Scaife Foundations and CMRF of the University of Pittsburgh Medical Center (to Y.L.), and American Cancer Society (RSG-03-169-TBE to Y.J.).

Keywords

  • EGFR
  • Endosomal trafficking
  • PX domain
  • Phosphoinositides
  • Sorting nexin 1
  • Sorting nexin 5

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry
  • Cell Biology

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