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mTORC2 phosphorylates protein kinase Cζ to regulate its stability and activity

Xin Li, Tianyan Gao

Author Affiliations

  1. Xin Li1 and
  2. Tianyan Gao*,1,2
  1. 1Markey Cancer Center, University of Kentucky, Lexington, KY, USA
  2. 2Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA
  1. *Corresponding author: Tel: +1 859 323 3454; Fax: +1 859 257 6030; E‐mail: tianyan.gao{at}
View Abstract


Protein kinase Cζ (PKCζ) is phosphorylated at the activation loop and the turn motif (TM). However, the TM kinase and functional relevance of TM phosphorylation remain largely unknown. We demonstrate that PKCζ TM is phosphorylated directly by the mTORC2 complex, and this phosphorylation is required for maintaining PKCζ kinase activity and stability. Functionally, mTORC2 regulates the activity of Rho family of GTPases, and therefore the organization of the actin cytoskeleton, through the control of PKCζ activity. Taken together, our findings identify PKCζ as a novel substrate and downstream effector of mTORC2 signaling.


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PKCζ is identified as a target of mTORC2, phosphorylation by which prevents PKCζ ubiquitination and degradation, and promotes kinase activity. mTORC2‐mediated control of Rho GTPase activity and actin cytoskeleton dynamics depends on this PKCζ phosphorylation.

  • mTORC2 phosphorylates the turn motif of PKCζ at Thr560

  • Phosphorylation of PKCζ downstream of mTORC2 signaling controls proper activation of Rac1, Cdc42 and RhoA

  • Thr560 phosphorylation is necessary for accurate organization of actin cytoskeleton and lamellipodia formation

  • Received April 2, 2013.
  • Revision received October 8, 2013.
  • Accepted October 22, 2013.
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