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Protein kinase C: release from quarantine by mTORC2
Timothy R Baffi1, Alexandra C Newton2
1Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093, USA; Division of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92093, USA.
Trends in Biochemical Sciences
|April 1, 2022
Summary
Protein kinase C (PKC) is primed for signaling through a newly discovered TOR interaction motif (TIM) and mechanistic target of rapamycin complex 2 (mTORC2) mediated phosphorylation. This process activates PKC by releasing its autoinhibitory pseudosubstrate.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Signaling
Background:
- Protein kinase C (PKC) isozymes exist in an autoinhibited state, requiring activation by second messengers.
- PKC activation involves a 'ready-to-go' conformation achieved through complex priming phosphorylations, the mechanism of which was previously unclear.
Purpose of the Study:
- To elucidate the enigmatic mechanism of PKC priming phosphorylations.
- To highlight new insights into how phosphorylation controls PKC activity and AGC kinase regulation.
Main Methods:
- Review of recent findings on PKC phosphorylation.
- Analysis of the TOR interaction motif (TIM) and its role in PKC priming.
- Examination of mechanistic target of rapamycin complex 2 (mTORC2) involvement.
Main Results:
- A novel mechanism for PKC priming has been identified, involving the TOR interaction motif (TIM).
- Mechanistic target of rapamycin complex 2 (mTORC2) plays a crucial role in priming PKC through phosphorylation.
- Autophosphorylation is confirmed as a key mechanism in priming PKC for signaling.
Conclusions:
- Phosphorylation, mediated by mTORC2 and involving TIM, is essential for activating PKC by releasing its autoinhibitory pseudosubstrate.
- This study clarifies a critical step in PKC activation and provides context for AGC kinase regulation.
- Understanding these phosphorylation events offers new perspectives on cellular signaling pathways controlled by PKC.
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