Protein Kinase C as a Molecular Machine for Decoding Calcium and Diacylglycerol Signals
Open accessAbstract
The specificity of many signal transduction pathways relies on the temporal coordination of different second messenger signals. Here we found a molecular mechanism which guarantees that conventional protein kinase C (PKC) isoforms are sequentially activated by calcium and diacylglycerol signals. Receptor stimuli that triggered repetitive calcium spikes induced a parallel repetitive translocation of GFP-tagged PKCgamma to the plasma membrane. While calcium acted rapidly, diacylglycerol binding to PKCgamma was initially prevented by a pseudosubstrate clamp, which kept the diacylglycerol-binding site inaccessible and delayed calcium- and diacylglycerol-mediated kinase activation. After termination of calcium signals, bound diacylglycerol prolonged kinase activity. The properties of this molecular decoding machine make PKCgamma responsive to persistent diacylglycerol increases combined with high- but not low-frequency calcium spikes.
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Chimeric constructs of GFP with defined lipid-binding domains of proteins can monitor the distribution of phospholipids and their metabolites in transfected cells.
“Recent and elegant reports have introduced the use of chimeric constructs of GFP with defined lipid-binding domains of proteins to monitor the distribution of phospholipids and their metabolites in transfected cells (Oancea and Meyer 1998; Oancea et al. 1998; Stauffer et al. 1998; Varnai et al. 1999; Czech 2000).”
From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Oancea and Meyer 1998
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- Authors
- Oancea, E., & Meyer, T.
- Affiliations
- Duke Medical Center (US)
- Corresponding author
- Meyer, Tobias
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1998-10
- Volume
- 95
- Issue
- 3
- Pages
- 307-318
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2097331211
- Cited by
- 640
- References
- 0
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 6 · 2023: 9 · 2022: 6 · 2021: 9 · 2020: 9 · 2019: 10 · 2018: 18 · 2017: 15 · 2016: 16 · 2015: 20 · 2014: 22 · 2013: 28 · 2012: 22
- FWCI
- 10.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01gm051457-04)
- National Institute of General Medical Sciences (GM 51457)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- protein kinase C, PKC gamma, calcium signaling, diacylglycerol, second messenger signaling, signal decoding, pseudosubstrate, plasma membrane translocation, kinase activation, calcium spikes
- MeSH terms
- Animals, Binding Sites, Calcium, Cell Membrane, Cytosol, Diglycerides, Enzyme Activation, Isoenzymes, Kinetics, Luminescent Proteins, Microscopy, Fluorescence, Models, Biological, Protein Kinase C, Recombinant Fusion Proteins, Substrate Specificity, Tumor Cells, Cultured, Phorbol 12,13-Dibutyrate, Signal Transduction, Calcium Signaling, Catalytic Domain, Green Fluorescent Proteins
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