ArticleBritish journal of haematology2020
Inhibition of Band 3 tyrosine phosphorylation: a new mechanism for treatment of sickle cell disease.
Article in British journal of haematology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Safety, Pharmacokinetics, and Pharmacodynamics of Etavopivat (FT-4202), an Allosteric Activator of Pyruvate Kinase-R, in Healthy Adults: A Randomized, Placebo-Controlled, Double-Blind, First-in-Human Phase 1 Trial.Clinical pharmacology in drug development · 2022Trial
- Identification of scavenger receptor BI as a scavenger of free heme that is essential for protection against hemolysis.Nature communications · 2026Article
- Repurposing Tyrosine Kinase Inhibitors for Sickle Cell Disease: Focus on Band 3 Phosphorylation.Biomedicines · 2026Review
- Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities.Comprehensive Physiology · 2026Review
- SIRPα extracellular domain shed from neutrophils by ADAM10 aggravates sepsis via initiating nitric oxide release from erythrocyte.Journal of advanced research · 2026Article
- Mitapivat for sickle cell disease: the time is ripe for a new therapy.Annals of translational medicine · 2026Article
- Post-translational Modifications in Proteins: Prediction Methods, Biological Functions, and Diseases.MedComm · 2026Review
- An overview of hereditary spherocytosis and the curative effects of splenectomy.Frontiers in physiology · 2025Review
- Epicatechin Influence on Biochemical Modification of Human Erythrocyte Metabolism and Membrane Integrity.International journal of molecular sciences · 2024Article
- Activating pyruvate kinase improves red blood cell integrity by reducing band 3 tyrosine phosphorylation.Blood advances · 2024Article
- Article
- Tyrosine phosphorylation of band 3 impairs the storage quality of suspended red blood cells in the Tibetan high-altitude polycythemia population.Journal of translational medicine · 2023Article
- Catch bonds in sickle cell disease: Shear-enhanced adhesion of red blood cells to laminin.Biophysical journal · 2023Article
- Sickle red blood cell-derived extracellular vesicles activate endothelial cells and enhance sickle red cell adhesion mediated by von Willebrand factor.British journal of haematology · 2023Article
- In Humanized Sickle Cell Mice, Imatinib Protects Against Sickle Cell-Related Injury.HemaSphere · 2023Article
- A microfluidic device for assessment of E-selectin-mediated neutrophil recruitment to inflamed endothelium and prediction of therapeutic response in sickle cell disease.Biosensors & bioelectronics · 2023Article
- Erythrocyte mitogen-activated protein kinases mediate hemolytic events under osmotic and oxidative stress and in hemolytic diseases.Cellular signalling · 2022Article
- Cardiovascular consequences of sickle cell disease.Biophysics reviews · 2022Review
- Antithrombin-III mitigates thrombin-mediated endothelial cell contraction and sickle red blood cell adhesion in microscale flow.British journal of haematology · 2022Article
- Rapid degradation of protein tyrosine phosphatase 1B in sickle cells: Possible contribution to sickle cell membrane weakening.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
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13 authors at 7 institutions in 2 countries.
Funding
Abstract
Many hypotheses have been proposed to explain how a glutamate to valine substitution in sickle haemoglobin (HbS) can cause sickle cell disease (SCD). We propose and document a new mechanism in which elevated tyrosine phosphorylation of Band 3 initiates sequelae that cause vaso-occlusion and the symptoms of SCD. In this mechanism, denaturation of HbS and release of heme generate intracellular oxidants which cause inhibition of erythrocyte tyrosine phosphatases, thus permitting constitutive tyrosine phosphorylation of Band 3. This phosphorylation in turn induces dissociation of the spectrin-actin cytoskeleton from the membrane, leading to membrane weakening, discharge of membrane-derived microparticles (which initiate the coagulation cascade) and release of cell-free HbS (which consumes nitric oxide) and activates the endothelium to express adhesion receptors). These processes promote vaso-occlusive events which cause SCD. We further show that inhibitors of Syk tyrosine kinase block Band 3 tyrosine phosphorylation, prevent release of cell-free Hb, inhibit discharge of membrane-derived microparticles, increase sickle cell deformability, reduce sickle cell adhesion to human endothelial cells, and enhance sickle cell flow through microcapillaries. In view of reports that imatinib (a Syk inhibitor) successfully treats symptoms of sickle cell disease, we suggest that Syk tyrosine kinase inhibitors warrant repurposing as potential treatments for SCD.
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