ArticleThe Journal of biological chemistry2010
Protein kinase Ctheta negatively regulates store-independent Ca2+ entry and phosphatidylserine exposure downstream of glycoprotein VI in platelets.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Suppressed ORAI1-STIM1-dependent CaThe Journal of biological chemistry · 2024Article
- Sodium bicarbonate as a local adjunctive agent for limiting platelet activation, aggregation, and adhesion within cardiovascular therapeutic devices.Journal of thrombosis and thrombolysis · 2023Article
- Platelet-Derived Extracellular Vesicles in Arterial Thrombosis.Advances in experimental medicine and biology · 2023Article
- Mechanisms Underlying Dichotomous Procoagulant COAT Platelet Generation-A Conceptual Review Summarizing Current Knowledge.International journal of molecular sciences · 2022Review
- Blood platelets stimulate cancer extravasation through TGFβ-mediated downregulation of PRH/HHEX.Oncogenesis · 2020Article
- Supramaximal calcium signaling triggers procoagulant platelet formation.Blood advances · 2020Article
- Negative regulators of platelet activation and adhesion.Journal of thrombosis and haemostasis : JTH · 2018Review
- Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer.BMC cancer · 2016Article
- The role of plasma membrane STIM1 and Ca(2+)entry in platelet aggregation. STIM1 binds to novel proteins in human platelets.Cellular signalling · 2014Article
- RhoG protein regulates platelet granule secretion and thrombus formation in mice.The Journal of biological chemistry · 2013Article
- Tyrosine phosphorylation on spleen tyrosine kinase (Syk) is differentially regulated in human and murine platelets by protein kinase C isoforms.The Journal of biological chemistry · 2013Article
- Article
- Signalling properties of inorganic polyphosphate in the mammalian brain.Nature communications · 2013Article
- Intervention of PKC-θ as an immunosuppressive regimen.Frontiers in immunology · 2012Article
- Submaximal inhibition of protein kinase C restores ADP-induced dense granule secretion in platelets in the presence of Ca2+.The Journal of biological chemistry · 2011Article
- Critical role for CD38-mediated Ca2+ signaling in thrombin-induced procoagulant activity of mouse platelets and hemostasis.The Journal of biological chemistry · 2011Article
- Signaling during platelet adhesion and activation.Arteriosclerosis, thrombosis, and vascular biology · 2010Review
- The protective effects of curcumin in cerebral ischemia and reperfusion injury through PKC-θ signaling.Cell cycle (Georgetown, Tex.)Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Platelet activation must be tightly controlled to provide an effective, but not excessive, response to vascular injury. Cytosolic calcium is a critical regulator of platelet function, including granule secretion, integrin activation, and phosphatidylserine (PS) exposure. Here we report that the novel protein kinase C isoform, PKCtheta, plays an important role in negatively regulating Ca(2+) signaling downstream of the major collagen receptor, glycoprotein VI (GPVI). This limits PS exposure and so may prevent excessive platelet procoagulant activity. Stimulation of GPVI resulted in significantly higher and more sustained Ca(2+) signals in PKCtheta(-/-) platelets. PKCtheta acts at multiple distinct sites. PKCtheta limits secretion, reducing autocrine ADP signaling that enhances Ca(2+) release from intracellular Ca(2+) stores. PKCtheta thereby indirectly regulates activation of store-operated Ca(2+) entry. However, PKCtheta also directly and negatively regulates store-independent Ca(2+) entry. This pathway, activated by the diacylglycerol analogue, 1-oleoyl-2-acetyl-sn-glycerol, was enhanced in PKCtheta(-/-) platelets, independently of ADP secretion. Moreover, LOE-908, which blocks 1-oleoyl-2-acetyl-sn-glycerol-induced Ca(2+) entry but not store-operated Ca(2+) entry, blocked the enhanced GPVI-dependent Ca(2+) signaling and PS exposure seen in PKCtheta(-/-) platelets. We propose that PKCtheta normally acts to restrict store-independent Ca(2+) entry during GPVI signaling, which results in reduced PS exposure, limiting platelet procoagulant activity during thrombus formation.
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Registered trials
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.