{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T22:27:51Z","timestamp":1782512871835,"version":"3.54.5"},"reference-count":21,"publisher":"Georg Thieme Verlag KG","issue":"08","license":[{"start":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T00:00:00Z","timestamp":1644883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"European Union's Horizon 2020 Research and Innovation Program","award":["766118"],"award-info":[{"award-number":["766118"]}]},{"name":"British Heart Foundation Chair","award":["CH03\/003"],"award-info":[{"award-number":["CH03\/003"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["204951\/Z\/16\/Z"],"award-info":[{"award-number":["204951\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"crossref","award":["PID2019\u2013108727RB-I00"],"award-info":[{"award-number":["PID2019\u2013108727RB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Interdisciplinary Center of Clinical Research (IZKF) of the University of M\u00fcnster","award":["Ebl-A\/009\/21"],"award-info":[{"award-number":["Ebl-A\/009\/21"]}]},{"DOI":"10.13039\/501100008425","name":"Conseller\u00eda de Cultura, Educaci\u00f3n e Ordenaci\u00f3n Universitaria, Xunta de Galicia","doi-asserted-by":"crossref","award":["ED431G 2019\/02"],"award-info":[{"award-number":["ED431G 2019\/02"]}],"id":[{"id":"10.13039\/501100008425","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Background\u2003CLEC-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.<\/jats:p><jats:p>Objectives\u2003To identify novel CLEC-2 small-molecule ligands to aid therapeutic targeting of CLEC-2.<\/jats:p><jats:p>Methods\u2003ALPHA screen technology has been used for the development of a high-throughput screening (HTS) assay recapitulating the podoplanin\u2013CLEC-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.<\/jats:p><jats:p>Results and Conclusion\u2003We developed a CLEC-2\u2013podoplanin 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\u2009F(ab)\u20322. Katacine is a novel nonprotein ligand of CLEC-2 that could contribute to a better understanding of CLEC-2 activation in human platelets.<\/jats:p>","DOI":"10.1055\/a-1772-1069","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T01:33:31Z","timestamp":1644975211000},"page":"1361-1368","source":"Crossref","is-referenced-by-count":10,"title":["Katacine Is a New Ligand of CLEC-2 that Acts as a Platelet Agonist"],"prefix":"10.1055","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5232-3376","authenticated-orcid":false,"given":"Luis A.","family":"Mor\u00e1n","sequence":"additional","affiliation":[{"name":"Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, and Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain"},{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Di","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin A.","family":"Sowa","sequence":"additional","affiliation":[{"name":"Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, and Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain"},{"name":"Institute for Cardiovascular and Metabolic Research (ICMR), School of Biological Sciences, University of Reading, Reading, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Hermida-Nogueira","sequence":"additional","affiliation":[{"name":"Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, and Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1701-6899","authenticated-orcid":false,"given":"Mar\u00eda N.","family":"Barrachina","sequence":"additional","affiliation":[{"name":"Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, and Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleyna","family":"Martin","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1912-7816","authenticated-orcid":false,"given":"Joanne C.","family":"Clark","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd H.","family":"Mize","sequence":"additional","affiliation":[{"name":"Advanced Mass Spectrometry Facility, Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9156-2137","authenticated-orcid":false,"given":"Johannes A.","family":"Eble","sequence":"additional","affiliation":[{"name":"Institute for Physiological Chemistry and Pathobiochemistry, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Moreira","sequence":"additional","affiliation":[{"name":"Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, and Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8706-5154","authenticated-orcid":false,"given":"Alice Y.","family":"Pollitt","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular and Metabolic Research (ICMR), School of Biological Sciences, University of Reading, Reading, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda I.","family":"Loza","sequence":"additional","affiliation":[{"name":"Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, and Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, and Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7846-7423","authenticated-orcid":false,"given":"Steve P.","family":"Watson","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1176-5917","authenticated-orcid":false,"given":"\u00c1ngel","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Center for Research in Molecular Medicine and Chronic 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