The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C

  • Facchinetti V
  • Ouyang W
  • Wei H
 et al. 
  • 12


    Mendeley users who have this article in their library.
  • 309


    Citations of this article.


The target of rapamycin (TOR), as part of the rapamycin-sensitive TOR complex 1 (TORC1), regulates various aspects of protein synthesis. Whether TOR functions in this process as part of TORC2 remains to be elucidated. Here, we demonstrate that mTOR, SIN1 and rictor, components of mammalian (m) TORC2, are required for phosphorylation of Akt and conventional protein kinase C (PKC) at the turn motif (TM) site. This TORC2 function is growth factor independent and conserved from yeast to mammals. TM site phosphorylation facilitates carboxyl-terminal folding and stabilizes newly synthesized Akt and PKC by interacting with conserved basic residues in the kinase domain. Without TM site phosphorylation, Akt becomes protected by the molecular chaperone Hsp90 from ubiquitination-mediated proteasome degradation. Finally, we demonstrate that mTORC2 independently controls the Akt TM and HM sites in vivo and can directly phosphorylate both sites in vitro. Our studies uncover a novel function of the TOR pathway in regulating protein folding and stability, processes that are most likely linked to the functions of TOR in protein synthesis.

Author-supplied keywords

  • Akt
  • PKC
  • Protein folding
  • Turn motif
  • mTOR

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text


  • Valeria Facchinetti

  • Weiming Ouyang

  • Hua Wei

  • Nelyn Soto

  • Adam Lazorchak

  • Christine Gould

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free