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Updated: Oct 1, 2025

Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy
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Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy

Published on: September 11, 2015

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O-GlcNAcylation regulates epidermal growth factor receptor intracellular trafficking and signaling

Liming Wu1, Yaxian Cheng2, Didi Geng2

  • 1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang Provincial Key Laboratory of Pancreatic Disease, School of Medicine, Zhejiang University, Hangzhou 310003, China.

Proceedings of the National Academy of Sciences of the United States of America
|March 3, 2022
PubMed

Insights

A sugar modification on hepatocyte growth factor regulated tyrosine kinase substrate (HGS) blocks epidermal growth factor receptor (EGFR) degradation. This prolonged EGFR signaling impacts diseases like cancer, obesity, and diabetes.

Area of Science:

  • Cell biology
  • Molecular signaling
  • Biochemistry

Background:

  • Epidermal growth factor receptor (EGFR) signaling is crucial for cell growth, proliferation, and survival.
  • EGFR signal termination involves internalization, endosomal trafficking, and lysosomal degradation.
  • The precise regulation of EGFR trafficking remains incompletely understood.

Purpose of the Study:

  • To investigate the regulatory mechanisms of EGFR trafficking.
  • To elucidate the role of hepatocyte growth factor regulated tyrosine kinase substrate (HGS) in EGFR signal termination.
  • To understand how post-translational modifications of HGS affect EGFR trafficking.

Main Methods:

  • Investigated the post-translational modification of HGS.
  • Utilized cell-based assays to track EGFR trafficking.
  • Analyzed the impact of HGS modification on EGFR localization and signaling.

Main Results:

  • Demonstrated that HGS is dynamically modified by N-acetylglucosamine.
  • Showed that this N-acetylglucosamine modification inhibits EGFR trafficking from endosomes to lysosomes.
  • Observed accumulation of EGFR and prolonged signaling due to inhibited degradation.

Conclusions:

  • Single N-acetylglucosamine modification of HGS is a critical regulator of EGFR trafficking.
  • Inhibition of EGFR degradation by modified HGS has implications for diseases with aberrant growth factor signaling.
  • This finding offers new insights into the pathogenesis of cancer, obesity, and diabetes.
Keywords:
EGFRO-GlcNAcylationendosomal sortingmembrane receptors

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