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. 2011 Nov;23(11):1824-30.
doi: 10.1016/j.cellsig.2011.06.018. Epub 2011 Jul 13.

Akt Phosphorylation at Thr308 and Ser473 Is Required for CHIP-mediated Ubiquitination of the Kinase

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Akt Phosphorylation at Thr308 and Ser473 Is Required for CHIP-mediated Ubiquitination of the Kinase

Chih-Hao Su et al. Cell Signal. .

Abstract

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.

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