Akt phosphorylation at Thr308 and Ser473 is required for CHIP-mediated ubiquitination of the kinase

作者：Su Chih Hao; Wang Cheng Yi; Lan Keng Hsin; Li Chung Pin; Chao Yee; Lin Han Chieh; Lee Shou Dong; Lee Wei Ping^*

来源：Cellular Signalling, 2011, 23(11): 1824-1830.

DOI：10.1016/j.cellsig.2011.06.018

• Akt
• Hsp90
• CHIP
• Proteasome

Phosphorylation at Thr308 and Ser473 is known to activate Akt, a major kinase in mammalian cells. Once activated to turn on downstream signaling pathways, Akt returns to an inactive pool via PP2A-mediated dephosphorylation. We show here that Thr308 and Ser473 phosphorylations prompt Akt to enter the CHIP-mediated ubiquitin-proteasome pathway. Mutation at either Thr308 or Ser473 dampened its ability to bind to the U-box E3 ligase CHIP (C-terminal Hsp70 -interacting protein), and the Akt mutants revealed decreased rate of ubiquitination by CHIP. Our study unveils that the well-known phosphorylations responsible for Akt activation turn out to transduce recognition signals for Akt-CHIP binding and ensuing degradation.

• 出版日期2011-11