ArticleJournal of thrombosis and haemostasis : JTH2014
The β isoform of the catalytic subunit of protein phosphatase 2B restrains platelet function by suppressing outside-in αII b β3 integrin signaling.
Article in Journal of thrombosis and haemostasis : JTH, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
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- How Protein Depletion Balances Thrombosis and Bleeding Risk in the Context of Platelet's Activatory and Negative Signaling.International journal of molecular sciences · 2024Review
- Protective effects of curcumin on desipramine-induced islet β-cell damage via AKAP150/PKA/PP2B complex.Acta pharmacologica Sinica · 2024Article
- Depression proteomic profiling in adolescents with transcriptome analyses in independent cohorts.Frontiers in psychiatry · 2024Article
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- mTOR regulates GPVI-mediated platelet activation.Journal of translational medicine · 2021Article
- Calcineurin Aβ-Specific Anchoring Confers Isoform-Specific Compartmentation and Function in Pathological Cardiac Myocyte Hypertrophy.Circulation · 2020Article
- Calcineurin-AKAP interactions: therapeutic targeting of a pleiotropic enzyme with a little help from its friends.The Journal of physiology · 2020Review
- Wdr-1 is essential for F-actin interaction with focal adhesions in platelets.Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis · 2018Article
- Fluorescent labeling of endogenous platelets for intravital microscopy: Effects on platelet function.Microcirculation (New York, N.Y. : 1994) · 2018Article
- Functional cyclophilin D moderates platelet adhesion, but enhances the lytic resistance of fibrin.Scientific reports · 2018Article
- Unlocking Aspirin's Chemopreventive Activity: Role of Irreversibly Inhibiting Platelet Cyclooxygenase-1.Cancer prevention research (Philadelphia, Pa.) · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCalcium-dependent signaling mechanisms play a critical role in platelet activation. Unlike calcium-activated protease and kinase, the contribution of calcium-activated protein serine/threonine phosphatase in platelet activation is poorly understood.
objectiveTo assess the role of catalytic subunit of protein phosphatase 2B (PP2B) or calcineurin in platelet function.
resultsHere, we showed that an increase in PP2B activity was associated with agonist-induced activation of human and murine platelets. Pharmacological inhibitors of the catalytic subunit of protein phosphatase 2B (PP2B-A) such as cyclosporine A or tacrolimus (FK506) potentiated aggregation of human platelets. Murine platelets lacking the β isoform of PP2B-A (PP2B-Aβ(-/-) ) displayed increased aggregation with low doses of agonist concentrations. Loss of PP2B-Aβ did not affect agonist-induced integrin αII b β3 inside-out signaling, but increased basal Src activation and outside-in αII b β3 signaling to p38 mitogen-activated protein kinase (MAPK), with a concomitant enhancement in platelet spreading on immobilized fibrinogen and greater fibrin clot retraction. Fibrinogen-induced increased p38 activation in PP2B-Aβ(-/-) platelets were blocked by Src inhibitor. Both PP2B-Aβ(-/-) platelets and PP2B-Aβ-depleted human embryonal kidney 293 αII b β3 cells displayed increased adhesion to immobilized fibrinogen. Filamin A, an actin crosslinking phosphoprotein that is known to associate with β3 , was dephosphorylated on Ser(2152) in fibrinogen-adhered wild-type but not in PP2B-Aβ(-/-) platelets. In a FeCl3 injury thrombosis model, PP2B-Aβ(-/-) mice showed decreased time to occlusion in the carotid artery.
conclusionThese observations indicate that PP2B-Aβ by suppressing outside-in αII b β3 integrin signaling limits platelet response to vascular injury.
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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.