ArticleArteriosclerosis, thrombosis, and vascular biology2012
Protein kinase C isoform ε negatively regulates ADP-induced calcium mobilization and thromboxane generation in platelets.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 56 citations in OpenAlex.
- TNIK as a molecular switch regulating platelet function in hemostasis and hyperlipidemia-associated thrombosis.Blood advances · 2026Article
- Mendelian randomization identifies causal effects of phospholipids on portal vein thrombosis risk: FADS1/2-mediated pathways and their potential as diagnostic biomarkers.Nutrition & metabolism · 2026Article
- Neuroprotective effects of Apigenin on prenatal Valproic acid-induced autism spectrum disorder in rats.IBRO neuroscience reports · 2024Article
- Involvement of platelet signaling pathways in colorectal cancer and new therapeutic targets.American journal of cancer research · 2024Review
- Reversible Platelet Integrin αIIbβ3 Activation and Thrombus Instability.International journal of molecular sciences · 2022Review
- The Predominant Role of Arrestin3 in General GPCR Desensitization in Platelets.Journal of clinical medicine · 2021Article
- mTOR regulates GPVI-mediated platelet activation.Journal of translational medicine · 2021Article
- CaNaunyn-Schmiedeberg's archives of pharmacology · 2020Article
- Prevention of platelet aggregation and arterial thrombosis using a modified Shenzhu Guanxin Formula.The Journal of international medical research · 2020Article
- Role of GRK6 in the Regulation of Platelet Activation through Selective G Protein-Coupled Receptor (GPCR) Desensitization.International journal of molecular sciences · 2020Article
- Responses of Plasma Catecholamine, Serotonin, and the Platelet Serotonin Transporter to Cigarette Smoking.Frontiers in neuroscience · 2019Review
- TC21/RRas2 regulates glycoprotein VI-FcRγ-mediated platelet activation and thrombus stability.Journal of thrombosis and haemostasis : JTH · 2018Article
- PDK1 governs thromboxane generation and thrombosis in platelets by regulating activation of Raf1 in the MAPK pathway.Journal of thrombosis and haemostasis : JTH · 2018Article
- PKC-epsilon deficiency alters progenitor cell populations in favor of megakaryopoiesis.PloS one · 2017Article
- Greater collagen-induced platelet aggregation following cyclooxygenase 1 inhibition predicts incident acute coronary syndromes.Clinical and translational science · 2015Article
- Article
- Platelet aggregation measurement for assessment of hemostasis failure mechanisms in patients with gastroduodenal ulcer bleeding.Clinical and experimental gastroenterology · 2013Article
- Protein kinase Cε and protein kinase Cθ double-deficient mice have a bleeding diathesis.Journal of thrombosis and haemostasis : JTH · 2012Article
- Protein kinase C ε expression in platelets from patients with acute myocardial infarction.PloS one · 2012Article
- Phosphorylation of protein kinase Cδ Tyr311 positively regulates thromboxane generation in platelets.The Journal of biological chemistryArticle
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
objectiveMembers of the protein kinase C (PKC) family are shown to positively and negatively regulate platelet activation. Although positive regulatory roles are extensively studied, negative regulatory roles of PKCs are poorly understood. We investigated the mechanism and specific isoforms involved in PKC-mediated negative regulation of ADP-induced functional responses. METHODS AND
resultsA pan-PKC inhibitor, GF109203X, potentiated ADP-induced cPLA(2) phosphorylation and thromboxane generation as well as ERK activation and intracellular calcium (Ca(2+)(i)) mobilization, 2 signaling molecules, upstream of cPLA(2) activation. Thus, PKCs inhibit cPLA(2) activation by inhibiting ERK and Ca(2+)(i) mobilization. Because the inhibitor of classic PKC isoforms, GO-6976, did not affect ADP-mediated thromboxane generation, we investigated the role of novel class of PKC isoforms. ADP-induced thromboxane generation, calcium mobilization, and ERK phosphorylation were potentiated in PKCε null murine platelets compared with platelets from wild-type littermates. Interestingly, when thromboxane release is blocked, ADP-induced aggregation in PKCε knockout and wild-type was similar, suggesting that PKCε does not affect ADP-induced aggregation directly. PKCε knockout mice exhibited shorter times to occlusion in an FeCl(3)-induced arterial injury model and shorter bleeding times in tail-bleeding experiments.
conclusionsWe conclude that PKCε negatively regulates ADP-induced thromboxane generation in platelets and offers protection against thrombosis.
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