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Published on: February 21, 2019
Protein kinase C pharmacology: refining the toolbox
Alyssa X Wu-Zhang1, Alexandra C Newton
1Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0721, USA.
The Biochemical Journal
|May 14, 2013
Summary
Protein kinase C (PKC) pharmacology is complex due to numerous modulators. This review clarifies genuine and discredited PKC activators and inhibitors, aiding research on PKC signaling dynamics.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Protein kinase C (PKC) is a key target for tumor-promoting phorbol esters.
- Phorbol esters activate specific PKC isoenzymes, serving as pharmacological tools.
- PKC modulator research is complicated by off-target effects and complex isoenzyme interactions.
Purpose of the Study:
- To clarify the current status of bona fide and discredited PKC modulators.
- To address the complexities in PKC pharmacology and tool development.
- To guide researchers in selecting appropriate tools for studying PKC isoenzyme activity.
Main Methods:
- Literature review of PKC modulators (activators, inhibitors, peptides).
- Analysis of phorbol ester-responsive proteins and small-molecule compounds.
- Discussion of genetically encoded reporters and PKC mutants for spatiotemporal analysis.
Main Results:
- Many compounds initially thought to modulate PKC directly have off-target effects.
- Distinguishing isoenzyme-specific PKC activity remains challenging.
- Confusion exists regarding the reliability of current pharmacological tools for PKC modulation.
Conclusions:
- A critical evaluation of PKC modulators is necessary for accurate research.
- Understanding isoenzyme-specific effects is crucial for advancing PKC signaling studies.
- Genetically encoded reporters and mutants offer precise methods for assessing PKC activity.
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