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  • The EMBO Journal (2008) 27, 1919 - 1931
  • doi:10.1038/emboj.2008.119

Published online: 19 June 2008

Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling

Tsuneo Ikenoue1, Ken Inoki1, Qian Yang1,2, Xiaoming Zhou1 and Kun-Liang Guan1,2,3

  1. Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA
  2. Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA
  3. Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA

Correspondence to:

Kun-Liang Guan, Department of Pharmacology and Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Dr., La Jolla, CA 92093-0815, USA. Tel.: +1 858 822 7945; Fax: +1 858 534 7628; E-mail: kuguan@ucsd.edu

Received 30 January 2008; Accepted 28 May 2008

Protein kinase C (PKC) is involved in a wide array of cellular processes such as cell proliferation, differentiation and apoptosis. Phosphorylation of both turn motif (TM) and hydrophobic motif (HM) are important for PKC function. Here, we show that the mammalian target of rapamycin complex 2 (mTORC2) has an important function in phosphorylation of both TM and HM in all conventional PKCs, novel PKCalt epsilon as well as Akt. Ablation of mTORC2 components (Rictor, Sin1 or mTOR) abolished phosphorylation on the TM of both PKCalpha and Akt and HM of Akt and decreased HM phosphorylation of PKCalpha. Interestingly, the mTORC2-dependent TM phosphorylation is essential for PKCalpha maturation, stability and signalling. Our study demonstrates that mTORC2 is involved in post-translational processing of PKC by facilitating TM and HM phosphorylation and reveals a novel function of mTORC2 in cellular regulation.

  • Keywords:

    • Akt,
    • mTOR,
    • PKC,
    • TORC2