O-GlcNAcylation regulates epidermal growth factor receptor intracellular trafficking and signaling.
Proc Natl Acad Sci U S A
; 119(10): e2107453119, 2022 03 08.
Article
em En
| MEDLINE
| ID: mdl-35239437
ABSTRACT
SignificanceEpidermal 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endossomos
/
Transdução de Sinais
/
Lisossomos
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article