Beta1-Integrin-collagen interaction suppresses FoxO3a by the coordination of Akt and PP2A.

ABSTRACT: When cells attach to the extracellular matrix (ECM) a proliferation permissive signal is engaged. The mechanism involves activation of the integrin/PI3K/Akt signal pathway. FoxO3a is a transcriptional activator and inhibits cell proliferation via up-regulating the expression of the cell cycle inhibitor p27. Furthermore, it is known that activated Akt can suppress FoxO3a function. However, it is not known whether integrin interaction with the ECM regulates FoxO3a function. We examined whether the beta1-integrin-mediated signaling pathway promotes fibroblast proliferation via FoxO3a suppression. We found that when fibroblasts are attached to collagen, PTEN protein expression and activity are inhibited due to promotion of PTEN degradation. This decrease in PTEN function permits FoxO3a suppres

SUBMITTER: Nho RS 

PROVIDER: S-EPMC2863165 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature