mTORC2 phosphorylates protein kinase Cζ to regulate its stability and activity

Area of Science:

• Molecular Biology
• Cell Signaling
• Biochemistry

Background:

• Protein kinase Cζ (PKCζ) is known to be phosphorylated at its activation loop and turn motif (TM).
• The specific kinase responsible for TM phosphorylation and its functional significance have remained largely uncharacterized.

Purpose of the Study:

• To identify the kinase responsible for phosphorylating the turn motif of PKCζ.
• To elucidate the functional relevance of PKCζ turn motif phosphorylation in regulating kinase activity and cellular processes.

Main Methods:

• Biochemical assays to demonstrate direct phosphorylation of PKCζ by mTORC2.
• Analysis of PKCζ kinase activity and stability following mTORC2-mediated phosphorylation.
• Investigation of downstream effects on Rho GTPases and actin cytoskeleton organization.

Main Results:

• The mammalian target of rapamycin complex 2 (mTORC2) directly phosphorylates the turn motif of PKCζ.
• This phosphorylation event is critical for maintaining both the catalytic activity and stability of PKCζ.
• mTORC2, via PKCζ, regulates Rho family GTPases and consequently impacts actin cytoskeleton organization.

Conclusions:

• PKCζ is identified as a novel substrate of the mTORC2 complex.
• PKCζ acts as a downstream effector of mTORC2 signaling, linking mTORC2 to the regulation of the actin cytoskeleton.
• These findings establish a new regulatory axis within cellular signaling pathways.