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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
PubMed

Insights

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.
Keywords:
PKCautophosphorylationmTORC2phosphorylation

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