TRAF6-mediated regulation of the PI3 kinase (PI3K)-Akt-GSK3β cascade is required for TNF-induced cell survival

Kwiyeom Yoon, Eun Joo Jung, Soo Young Lee

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)118-121
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume371
Issue number1
DOIs
StatePublished - 20 Jun 2008

Keywords

  • Akt
  • Cell survival
  • GSK3β
  • PI3 kinase
  • TNF
  • TRAF6

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