期刊
CELLULAR SIGNALLING
卷 23, 期 11, 页码 1824-1830出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2011.06.018
关键词
Akt; Hsp90; CHIP; Proteasome
类别
资金
- National Science Council [NSC96-2314-B075-0720-MY3]
- Taipei Veterans General Hospital [VGH97C1-092, VGH97C1-063]
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. (C) 2011 Elsevier Inc. All rights reserved.
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