Open AccessO-GlcNAcylation regulates epidermal growth factor receptor intracellular trafficking and signaling
Author(s) -
Liming Wu,
Yaxian Cheng,
Didi Geng,
Zhiya Fan,
Bingyi Lin,
Qiang Zhu,
Jingchao Li,
Weijie Qin,
Wen Yi
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2107453119
Subject(s) - endosome , microbiology and biotechnology , epidermal growth factor receptor , epidermal growth factor , internalization , signal transduction , erbb3 , growth factor receptor , growth factor , hepatocyte growth factor receptor , biology , protein kinase b , receptor tyrosine kinase , intracellular , hepatocyte growth factor , chemistry , receptor , biochemistry , c met
Significance Epidermal growth factor receptor (EGFR) is one of the most important membrane receptors that transduce growth signals into cells to sustain cell growth, proliferation, and survival. EGFR signal termination is initiated by EGFR internalization, followed by trafficking through endosomes, and degradation in lysosomes. How this process is regulated is still poorly understood. Here, we show that hepatocyte growth factor regulated tyrosine kinase substrate (HGS), a key protein in the EGFR trafficking pathway, is dynamically modified by a single sugar N-acetylglucosamine. This modification inhibits EGFR trafficking from endosomes to lysosomes, leading to the accumulation of EGFR and prolonged signaling. This study provides an important insight into diseases with aberrant growth factor signaling, such as cancer, obesity, and diabetes.