ArticleCell communication and signaling : CCS2019
cAMP- and cGMP-elevating agents inhibit GPIbα-mediated aggregation but not GPIbα-stimulated Syk activation in human platelets.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 24 citations in OpenAlex.
- Review
- Discovery of platelet glycoprotein VI receptor antagonists and their neuroprotective activity: an in silico, in vitro, and in vivo study.3 Biotech · 2025Article
- Effect of phosphodiesterase inhibitors on platelet function.Biochemistry and biophysics reports · 2025Article
- Multi-phased Kinetics and Interaction of Protein Kinase Signaling in Glycoprotein VI-Induced Platelet αIIbβ3 Integrin Activation and Degranulation.Thrombosis and haemostasis · 2025Article
- Rattlesnake Roundup: Point-of-Care Thrombelastographic Methods Define the Molecular Impacts on Coagulation ofToxins · 2025Review
- A review of natural compounds to regulate platelet aggregation: molecular mechanism and research advance.Frontiers in pharmacology · 2025Review
- ACKR3 agonism induces heterodimerization with chemokine receptor CXCR4 and attenuates platelet function.European journal of clinical investigation · 2025Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines.Life (Basel, Switzerland) · 2024Review
- Novel Knowledge about Molecular Mechanisms of Heparin-Induced Thrombocytopenia Type II and Treatment Targets.International journal of molecular sciences · 2023Review
- Differential Regulation of GPVI-Induced Btk and Syk Activation by PKC, PKA and PP2A in Human Platelets.International journal of molecular sciences · 2023Article
- Article
- Article
- ML355 Modulates Platelet Activation and Prevents ABT-737 Induced Apoptosis in Platelets.The Journal of pharmacology and experimental therapeutics · 2022Article
- The Serine/Threonine Protein Phosphatase 2A (PP2A) Regulates Syk Activity in Human Platelets.International journal of molecular sciences · 2020Article
- Feedback Regulation of Syk by Protein Kinase C in Human Platelets.International journal of molecular sciences · 2019Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe glycoprotein (GP) Ib-IX-V complex is a unique platelet plasma membrane receptor, which is essential for platelet adhesion and thrombus formation. GPIbα, part of the GPIb-IX-V complex, has several physiological ligands such as von Willebrand factor (vWF), thrombospondin and distinct coagulation factors, which trigger platelet activation. Despite having an important role, intracellular GPIb-IX-V signaling and its regulation by other pathways are not well defined. Our aim was to establish the intracellular signaling response of selective GPIbα activation in human platelets, in particular the role of the tyrosine kinase Syk and its regulation by cAMP/PKA and cGMP/PKG pathways, respectively. We addressed this using echicetin beads (EB), which selectively bind to GPIbα and induce platelet aggregation.
methodsPurified echicetin from snake Echis carinatus venom was validated by mass spectrometry. Washed human platelets were incubated with EB, in the presence or absence of echicetin monomers (EM), Src family kinase (SFK) inhibitors, Syk inhibitors and the cAMP- and cGMP-elevating agents iloprost and riociguat, respectively. Platelet aggregation was analyzed by light transmission aggregometry, protein phosphorylation by immunoblotting. Intracellular messengers inositolmonophosphate (InsP1) and Ca
resultsEB-induced platelet aggregation was dependent on integrin α
conclusionEB and EM are specific agonists and antagonists, respectively, of GPIbα-mediated Syk activation leading to platelet aggregation. The cAMP/PKA and cGMP/PKG pathways do not inhibit but enhance GPIbα-/GPVI-initiated, SFK-dependent Syk activation, but strongly inhibit further downstream responses including aggregation. These data establish an important intracellular regulatory network induced by GPIbα.
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