ArticleThe Journal of biological chemistry2010
Functional divergence of platelet protein kinase C (PKC) isoforms in thrombus formation on collagen.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 123 citations in OpenAlex.
- Glaucocalyxin A inhibits platelet activation and thrombus formation preferentially via GPVI signaling pathway.PloS one · 2013Trial
- PKC isoforms in hematopoietic lineages and myeloid/lymphoid leukemias: mechanistic insights and therapeutic prospects.Frontiers in oncology · 2026Review
- Multi-phased Kinetics and Interaction of Protein Kinase Signaling in Glycoprotein VI-Induced Platelet αIIbβ3 Integrin Activation and Degranulation.Thrombosis and haemostasis · 2025Article
- Suppressed ORAI1-STIM1-dependent CaThe Journal of biological chemistry · 2024Article
- Platelet Activation Pathways Controlling Reversible Integrin αIIbβ3 Activation.TH open : companion journal to thrombosis and haemostasis · 2024Article
- Ultra-high throughput-based screening for the discovery of antiplatelet drugs affecting receptor dependent calcium signaling dynamics.Scientific reports · 2024Article
- Regulation of Glycoprotein VI-Dependent Platelet Activation and Thrombus Formation by Heparan Sulfate Proteoglycan Perlecan.International journal of molecular sciences · 2023Article
- A gain-of-function filamin A mutation in mouse platelets induces thrombus instability.Journal of thrombosis and haemostasis : JTH · 2022Article
- Reversible Platelet Integrin αIIbβ3 Activation and Thrombus Instability.International journal of molecular sciences · 2022Review
- Modulation of Glycoprotein VI and Its Downstream Signaling Pathways as an Antiplatelet Target.International journal of molecular sciences · 2022Review
- Mechanisms Underlying Dichotomous Procoagulant COAT Platelet Generation-A Conceptual Review Summarizing Current Knowledge.International journal of molecular sciences · 2022Review
- Hemostatic Effect of 20(S)-Panaxadiol by Induced Platelet Aggregation Depending on Calcium Signaling Pathway.BioMed research international · 2022Article
- mTOR regulates GPVI-mediated platelet activation.Journal of translational medicine · 2021Article
- NADPH Oxidases Are Required for Full Platelet Activation In Vitro and Thrombosis In Vivo but Dispensable for Plasma Coagulation and Hemostasis.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Long-term platelet priming after glycoprotein VI stimulation in comparison to Protease-Activating Receptor (PAR) stimulation.PloS one · 2021Article
- Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome.Scientific reports · 2020Article
- Molecular Drivers of Platelet Activation: Unraveling Novel Targets for Anti-Thrombotic and Anti-Thrombo-Inflammatory Therapy.International journal of molecular sciences · 2020Review
- The Implications for Cells of the Lipid Switches Driven by Protein-Membrane Interactions and the Development of Membrane Lipid Therapy.International journal of molecular sciences · 2020Review
- Supramaximal calcium signaling triggers procoagulant platelet formation.Blood advances · 2020Article
- Antithrombotic effect and action mechanism ofChinese medicine · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
Arterial thrombosis, a major cause of myocardial infarction and stroke, is initiated by activation of blood platelets by subendothelial collagen. The protein kinase C (PKC) family centrally regulates platelet activation, and it is becoming clear that the individual PKC isoforms play distinct roles, some of which oppose each other. Here, for the first time, we address all four of the major platelet-expressed PKC isoforms, determining their comparative roles in regulating platelet adhesion to collagen and their subsequent activation under physiological flow conditions. Using mouse gene knock-out and pharmacological approaches in human platelets, we show that collagen-dependent alpha-granule secretion and thrombus formation are mediated by the conventional PKC isoforms, PKCalpha and PKCbeta, whereas the novel isoform, PKC, negatively regulates these events. PKCdelta also negatively regulates thrombus formation but not alpha-granule secretion. In addition, we demonstrate for the first time that individual PKC isoforms differentially regulate platelet calcium signaling and exposure of phosphatidylserine under flow. Although platelet deficient in PKCalpha or PKCbeta showed reduced calcium signaling and phosphatidylserine exposure, these responses were enhanced in the absence of PKC. In summary therefore, this direct comparison between individual subtypes of PKC, by standardized methodology under flow conditions, reveals that the four major PKCs expressed in platelets play distinct non-redundant roles, where conventional PKCs promote and novel PKCs inhibit thrombus formation on collagen.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.