Cholesterol modulates type I/II TGF-ß receptor complexes and alters the balance between Smad and Akt signaling in hepatocytes.
Commun Biol
; 7(1): 8, 2024 01 02.
Article
em En
| MEDLINE
| ID: mdl-38168942
ABSTRACT
Cholesterol mediates membrane compartmentalization, affecting signaling via differential distribution of receptors and signaling mediators. While excessive cholesterol and aberrant transforming growth factor-ß (TGF-ß) signaling characterize multiple liver diseases, their linkage to canonical vs. non-canonical TGF-ß signaling remained unclear. Here, we subjected murine hepatocytes to cholesterol depletion (CD) or enrichment (CE), followed by biophysical studies on TGF-ß receptor heterocomplex formation, and output to Smad2/3 vs. Akt pathways. Prior to ligand addition, raft-dependent preformed heteromeric receptor complexes were observed. Smad2/3 phosphorylation persisted following CD or CE. CD enhanced phospho-Akt (pAkt) formation by TGF-ß or epidermal growth factor (EGF) at 5 min, while reducing it at later time points. Conversely, pAkt formation by TGF-ß or EGF was inhibited by CE, suggesting a direct effect on the Akt pathway. The modulation of the balance between TGF-ß signaling to Smad2/3 vs. pAkt (by TGF-ß or EGF) has potential implications for hepatic diseases and malignancies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-akt
/
Hepatopatias
Limite:
Animals
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Israel