mTORC 2 phosphorylates protein kinase Cζ to regulate its stability and activity

• DOI: 10.1002/embr.201338119
• Publication Date: 2013-12-27T20:57:05Z
• Authors: Xin Li; Tianyan Gao
• Keywords: 0303 health sciences; TOR Serine-Threonine Kinases; Amino Acid Motifs; Mechanistic Target of Rapamycin Complex 2; Cell Line; Mice; 03 medical and health sciences; HEK293 Cells; Multiprotein Complexes; Enzyme Stability; Animals; Humans; Phosphorylation; Protein Kinase C; Signal Transduction

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.