We recently demonstrated that the tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) helps maintenance of cell survival by regulating glycogen synthase kinase 3β (GSK3β) activity during TNF signaling. However, the molecular linkage between TRAF6 and GSK3β signaling is unknown. Herein, we showed that TRAF6 positively regulated cell survival by modulating PI3K-Akt-GSK3β cascades. In 3T3 cells lacking TRAF6, but not those lacking TRAF2, TNF stimulation led to prolonged hyperphosphorylation of Akt, which coincided with the activation of upstream PI3K. Pharmacologically blocking PI3K significantly inhibited Akt and GSK3β phosphorylation. Importantly, PI3K inhibition rescued cell death in TRAF6-null 3T3 cells. These data suggested TRAF6 regulates TNF-mediated cell survival through PI3K-Akt-GSK3β cascades.
|Number of pages||4|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - 20 Jun 2008|
Bibliographical noteFunding Information:
We thank Dr. Wen-Chen Yeh for providing TRAF2-deficient 3T3 cells. This work was supported in part by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2006-C00309), and by NCRC program of MOST/KOSEF (Grant No. R15-2006-020-00000-0) through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University. K.Y. was supported by BK21 fellowship.
- Cell survival
- PI3 kinase