ArticleBritish journal of pharmacology2007
Modulation of protein kinase C by curcumin; inhibition and activation switched by calcium ions.
Article in British journal of pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 63 citations in OpenAlex.
- Curcumin: multifaceted biological actions and therapeutic implications-a narrative review.Inflammopharmacology · 2025Review
- Review
- Functional characterization of nutraceuticals using spectral clustering: Centrality of caveolae-mediated endocytosis for management of nitric oxide and vitamin D deficiencies and atherosclerosis.Frontiers in nutrition · 2022Article
- The assessment of antidiabetic properties of novel synthetic curcumin analogues: α-amylase and α-glucosidase as the target enzymes.Journal of diabetes and metabolic disorders · 2020Article
- Compounds from Natural Sources as Protein Kinase Inhibitors.Biomolecules · 2020Review
- Article
- Classical Protein Kinase C: a novel kinase target in breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- Curcumin Acts as a Positive Allosteric Modulator ofThe Journal of pharmacology and experimental therapeutics · 2018Article
- Presenting a New Standard Drug Model for Turmeric and Its Prized Extract, Curcumin.International journal of inflammation · 2018Review
- Curcumin Inhibits Protein Kinase Cα Activity by Binding to Its C1 Domain.Biochemistry · 2016Article
- Polyphenol compounds and PKC signaling.Biochimica et biophysica acta · 2016Review
- NDS27 combines the effect of curcumin lysinate and hydroxypropyl-β-cyclodextrin to inhibit equine PKCδ and NADPH oxidase involved in the oxidative burst of neutrophils.FEBS open bio · 2014Article
- The natural stilbenoid piceatannol decreases activity and accelerates apoptosis of human neutrophils: involvement of protein kinase C.Oxidative medicine and cellular longevity · 2013Article
- Identification of Siah-interacting protein as a potential regulator of apoptosis and curcumin resistance.Oncogene · 2010Article
- Curcumin inhibits ACTH- and angiotensin II-stimulated cortisol secretion and Ca(v)3.2 current.Journal of natural products · 2009Article
- Purification and characterization of a new Ca2+-dependent protein kinase C in mussel (Mytilus galloprovincialis Lmk.) mantle.Molecular and cellular biochemistry · 2009Article
- Curcumin as a Natural Therapeutic Agent: A Rapid Review of Potential Clinical Uses and Mechanisms of Action.Iranian journal of pharmaceutical research : IJPRReview
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposePrevious studies have identified the natural polyphenol curcumin as a protein kinase C (PKC) inhibitor. In contrast, we found significant stimulation of PKC activity following curcumin treatment. Thus, the mechanism of curcumin interaction with PKC was investigated. EXPERIMENTAL APPROACH: We employed phosphorylation assays in the presence of soluble or membrane-bound PKC substrates, followed by SDS-PAGE, autoradiography and phosphorylation intensity measurements. KEY
resultsCurcumin inhibited PKC in the absence of membranes whereas stimulation was observed in the presence of membranes. Further analysis indicated that curcumin decreased PKC activity by competition with Ca(2+) stimulation of the kinase, resulting in inhibition of activity at lower Ca(2+) concentrations and stimulation at higher Ca(2+) concentrations. The role of the membrane is likely to be facilitation of Ca(2+)-binding to the kinase, thus relieving the curcumin inhibition observed at limited Ca(2+) concentrations. Curcumin was found to mildly stimulate the catalytic subunit of PKC, which does not require Ca(2+) for activation. In addition, studies on Ca(2+)-independent PKC isoforms as well as another curcumin target (the sarcoplasmic reticulum Ca(2+)-ATPase) confirmed a correlation between Ca(2+) concentration and the curcumin effects. CONCLUSIONS AND IMPLICATIONS: Curcumin competes with Ca(2+) for the regulatory domain of PKC, resulting in a Ca(2+)-dependent dual effect on the kinase. We propose that curcumin interacts with the Ca(2+)-binding domains in target proteins. To our knowledge, this is the first study that defines an interaction domain for curcumin, and provides a rationale for the broad specificity of this polyphenol as a chemopreventive drug.
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