ArticleBlood2011
Protein kinase C mediates platelet secretion and thrombus formation through protein kinase D2.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 60 citations in OpenAlex.
- ER-associated degradation pathway protein SEL1L plays an evolutionarily conserved role in platelet adhesion.The Journal of clinical investigation · 2026Article
- PKCα Induced the Generation of Extracellular Vesicles in Activated Platelets to Promote Breast Cancer Metastasis.International journal of biological sciences · 2024Article
- Loss of zinc transporters ZIP1 and ZIP3 augments platelet reactivity in response to thrombin and accelerates thrombus formationFrontiers in immunology · 2023Article
- Platelet-Derived Extracellular Vesicles in Arterial Thrombosis.Advances in experimental medicine and biology · 2023Article
- mTOR regulates GPVI-mediated platelet activation.Journal of translational medicine · 2021Article
- Protein Kinase D2 drives chylomicron-mediated lipid transport in the intestine and promotes obesity.EMBO molecular medicine · 2021Article
- Sanguinarine Attenuates Collagen-Induced Platelet Activation and Thrombus Formation.Biomedicines · 2021Article
- Phosphoproteomic identification of vasopressin-regulated protein kinases in collecting duct cells.British journal of pharmacology · 2021Article
- Embelin as a Novel Inhibitor of PKC in the Prevention of Platelet Activation and Thrombus Formation.Journal of clinical medicine · 2019Article
- The kinase PKD3 provides negative feedback on cholesterol and triglyceride synthesis by suppressing insulin signaling.Science signaling · 2019Article
- Comparative Analysis of Microfluidics Thrombus Formation in Multiple Genetically Modified Mice: Link to Thrombosis and Hemostasis.Frontiers in cardiovascular medicine · 2019Article
- Small GTPases in platelet membrane trafficking.Platelets · 2019Review
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- Identification of platelet function defects by multi-parameter assessment of thrombus formation.Nature communications · 2014Article
- Secrets of platelet exocytosis - what do we really know about platelet secretion mechanisms?British journal of haematology · 2013Article
- 12-lipoxygenase activity plays an important role in PAR4 and GPVI-mediated platelet reactivity.Thrombosis and haemostasis · 2013Article
- Thyrotropin regulates IL-6 expression in CD34+ fibrocytes: clear delineation of its cAMP-independent actions.PloS one · 2013Article
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12 authors at 4 institutions in 3 countries.
Funding
Abstract
Platelets are highly specialized blood cells critically involved in hemostasis and thrombosis. Members of the protein kinase C (PKC) family have established roles in regulating platelet function and thrombosis, but the molecular mechanisms are not clearly understood. In particular, the conventional PKC isoform, PKCα, is a major regulator of platelet granule secretion, but the molecular pathway from PKCα to secretion is not defined. Protein kinase D (PKD) is a family of 3 kinases activated by PKC, which may represent a step in the PKC signaling pathway to secretion. In the present study, we show that PKD2 is the sole PKD member regulated downstream of PKC in platelets, and that the conventional, but not novel, PKC isoforms provide the upstream signal. Platelets from a gene knock-in mouse in which 2 key phosphorylation sites in PKD2 have been mutated (Ser707Ala/Ser711Ala) show a significant reduction in agonist-induced dense granule secretion, but not in α-granule secretion. This deficiency in dense granule release was responsible for a reduced platelet aggregation and a marked reduction in thrombus formation. Our results show that in the molecular pathway to secretion, PKD2 is a key component of the PKC-mediated pathway to platelet activation and thrombus formation through its selective regulation of dense granule secretion.
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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.