ArticleJournal of thrombosis and haemostasis : JTH2013
Specific inhibition of ectodomain shedding of glycoprotein Ibα by targeting its juxtamembrane shedding cleavage site.
Article in Journal of thrombosis and haemostasis : JTH, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Nascent ADAM17 synthesis potentiates GPIbα cleavage in resting and stimulated stored platelets.Blood vessels, thrombosis & hemostasis · 2026Article
- Specific O-glycans in the mechanosensory domain of glycoprotein Ibα are important for its stability and function.Haematologica · 2023Article
- Autoinhibitory module underlies species difference in shear activation of von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2022Article
- Overlapping and unique substrate specificities of ST3GAL1 and 2 during hematopoietic and megakaryocytic differentiation.Blood advances · 2022Article
- Fast clearance of platelets in a commonly used mouse model for GPIbα is impeded by an anti-GPIbβ antibody derivative.Journal of thrombosis and haemostasis : JTH · 2022Article
- Desialylation of O-glycans activates von Willebrand factor by destabilizing its autoinhibitory module.Journal of thrombosis and haemostasis : JTH · 2022Article
- Differential regulation of the platelet GPIb-IX complex by anti-GPIbβ antibodies.Journal of thrombosis and haemostasis : JTH · 2021Article
- Activation of von Willebrand factor via mechanical unfolding of its discontinuous autoinhibitory module.Nature communications · 2021Article
- Short-Acting Anti-VWF (von Willebrand Factor) Aptamer Improves the Recovery, Survival, and Hemostatic Functions of Refrigerated Platelets.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry.Journal of visualized experiments : JoVE · 2019Article
- Force-Regulated Refolding of the Mechanosensory Domain in the Platelet Glycoprotein Ib-IX Complex.Biophysical journal · 2019Article
- Platelet heterogeneity in activation-induced glycoprotein shedding: functional effects.Blood advances · 2018Article
- Novel antibodies against GPIbα inhibit pulmonary metastasis by affecting vWF-GPIbα interaction.Journal of hematology & oncology · 2018Article
- Effect of Pneumatic Tubing System Transport on Platelet Apheresis Units.Cardiovascular engineering and technology · 2018Article
- Review
- Article
- Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- A discontinuous autoinhibitory module masks the A1 domain of von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2017Article
- SheddomeDB: the ectodomain shedding database for membrane-bound shed markers.BMC bioinformatics · 2017Review
- Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor.Nature communications · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundEctodomain shedding of glycoprotein Ibα (GPIbα), a proteolytic event in which metalloprotease ADAM17 cleaves the Gly464-Val465 bond and releases glycocalicin to the plasma, is considered a critical step in mediating clearance of stored platelets. Supporting evidence has largely come from studies using ADAM17 inhibitors. However, the definitive proof is lacking due to the broad substrate specificity of ADAM17.
aimTo achieve substrate-specific inhibition of GPIbα shedding.
methodsDevelopment of monoclonal antibodies that directly bind the sequence around the GPIbα shedding cleavage site and inhibit GPIbα shedding by blocking ADAM17 access to the cleavage site.
resultsSix anti-GPIbα monoclonal antibodies with varying binding affinities were obtained. The prototypic clone, designated 5G6, and its monomeric Fab fragment bind specifically purified GPIb-IX complex, human platelets, and transgenic murine platelets expressing human GPIbα. The clone 5G6 showed similar inhibitory potency as a widely used shedding inhibitor GM6001 in both constitutive and induced GPIbα shedding in human platelets. It does not recognize mouse GPIbα or inhibit shedding of other platelet receptors. Finally, 5G6 binding displays no detectable effect on platelet activation and aggregation.
conclusionsThe clone 5G6 specifically inhibits GPIbα shedding with no detectable effect on platelet functions. The method of substrate-specific shedding inhibition by macromolecular binding of the shedding cleavage site can be applicable to many other transmembrane receptors undergoing ectodomain shedding.
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