The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins.
J Cell Biol
; 166(2): 213-23, 2004 Jul 19.
Article
en En
| MEDLINE
| ID: mdl-15249583
Insulin-like growth factors elicit many responses through activation of phosphoinositide 3-OH kinase (PI3K). The tuberous sclerosis complex (TSC1-2) suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1), which generally requires PI3K signals for its activation. Here, we show that TSC1-2 is required for insulin signaling to PI3K. TSC1-2 maintains insulin signaling to PI3K by restraining the activity of S6K, which when activated inactivates insulin receptor substrate (IRS) function, via repression of IRS-1 gene expression and via direct phosphorylation of IRS-1. Our results argue that the low malignant potential of tumors arising from TSC1-2 dysfunction may be explained by the failure of TSC mutant cells to activate PI3K and its downstream effectors.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
Transducción de Señal
/
Fosfatidilinositol 3-Quinasas
/
Proteínas Supresoras de Tumor
/
Insulina
Límite:
Animals
Idioma:
En
Revista:
J Cell Biol
Año:
2004
Tipo del documento:
Article
Pais de publicación:
Estados Unidos