ArticleThrombosis and haemostasis2022
Katacine Is a New Ligand of CLEC-2 that Acts as a Platelet Agonist.
Article in Thrombosis and haemostasis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Hemin-induced platelet activation is regulated by the ACKR3 chemokine surface receptor and has implications for passivation of vulnerable atherosclerotic plaques.The FEBS journal · 2024Article
- Secondary Sites of the C-type Lectin-Like Fold.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Review
- C-type lectin-like receptor 2: roles and drug target.Thrombosis journal · 2024Review
- Factors Associated with Platelet Activation-Recent Pharmaceutical Approaches.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundCLEC-2 is a platelet receptor with an important role in thromboinflammation but a minor role in hemostasis. Two endogenous ligands of CLEC-2 have been identified, the transmembrane protein podoplanin and iron-containing porphyrin hemin, which is formed following hemolysis from red blood cells. Other exogenous ligands such as rhodocytin have contributed to our understanding of the role of CLEC-2.
objectivesTo identify novel CLEC-2 small-molecule ligands to aid therapeutic targeting of CLEC-2.
methodsALPHA screen technology has been used for the development of a high-throughput screening (HTS) assay recapitulating the podoplanin-CLEC-2 interaction. Light transmission aggregometry was used to evaluate platelet aggregation. Immunoprecipitation and western blot were used to evaluate direct phosphorylation of CLEC-2 and downstream protein phosphorylation. Autodock vina software was used to predict the molecular binding site of katacine and mass spectrometry to determine the polymeric nature of the ligand. RESULTS AND
conclusionWe developed a CLEC-2-podoplanin interaction assay in a HTS format and screened 5,016 compounds from a European Union-open screen library. We identified katacine, a mixture of polymers of proanthocyanidins, as a novel ligand for CLEC-2 and showed that it induces platelet aggregation and CLEC-2 phosphorylation via Syk and Src kinases. Platelet aggregation induced by katacine is inhibited by the anti-CLEC-2 monoclonal antibody fragment AYP1 F(ab)'2. Katacine is a novel nonprotein ligand of CLEC-2 that could contribute to a better understanding of CLEC-2 activation in human platelets.
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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.