| http://purl.uniprot.org/citations/25795918 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25795918 | http://www.w3.org/2000/01/rdf-schema#comment | "Platelet aggregation at sites of vascular injury is not only essential for hemostasis, but may also cause acute ischemic disease states such as myocardial infarction or stroke. The hemi-immunoreceptor tyrosine-based activation motif-containing C-type lectinlike receptor 2 (CLEC-2) mediates powerful platelet activation through a Src- and spleen tyrosine kinase (Syk)-dependent tyrosine phosphorylation cascade. Thereby, CLEC-2 not only contributes to thrombus formation and stabilization but also plays a central role in blood-lymphatic vessel development, tumor metastasis, and prevention of inflammatory bleeding, making it a potential pharmacologic target to modulate these processes. We have previously shown that injection of the anti-CLEC-2 antibody, INU1, results in virtually complete immunodepletion of platelet CLEC-2 in mice, which is, however, preceded by a severe transient thrombocytopenia thereby limiting its potential therapeutic use. The mechanisms underlying this targeted CLEC-2 downregulation have remained elusive. Here, we show that INU1-induced CLEC-2 immunodepletion occurs through Src-family kinase-dependent receptor internalization in vitro and in vivo, presumably followed by intracellular degradation. In mice with platelet-specific Syk deficiency, INU1-induced CLEC-2 internalization/degradation was fully preserved whereas the associated thrombocytopenia was largely prevented. These results show for the first time that CLEC-2 can be downregulated from the platelet surface through internalization in vitro and in vivo and that this can be mechanistically uncoupled from the associated antibody-induced thrombocytopenia."xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2014-11-611905"xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/author | "Witke W."xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/author | "Kiefer F."xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/author | "Nieswandt B."xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/author | "Watson S.P."xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/author | "Stritt S."xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/author | "Walzog B."xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/author | "Stegner D."xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/author | "Schymeinsky J."xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/author | "Vogtle T."xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/author | "Lorenz V."xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/pages | "4069-4077"xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/title | "Targeted downregulation of platelet CLEC-2 occurs through Syk-independent internalization."xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://purl.uniprot.org/core/volume | "125"xsd:string |
| http://purl.uniprot.org/citations/25795918 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25795918 |
| http://purl.uniprot.org/citations/25795918 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25795918 |
| http://purl.uniprot.org/uniprot/#_A0A0A6YVS1-mappedCitation-25795918 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25795918 |
| http://purl.uniprot.org/uniprot/#_A0T1G3-mappedCitation-25795918 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25795918 |
| http://purl.uniprot.org/uniprot/#_A2AIM2-mappedCitation-25795918 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25795918 |
| http://purl.uniprot.org/uniprot/#_E9PWE9-mappedCitation-25795918 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25795918 |
| http://purl.uniprot.org/uniprot/#_F6S1V7-mappedCitation-25795918 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25795918 |