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http://purl.uniprot.org/citations/30700416http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30700416http://www.w3.org/2000/01/rdf-schema#comment"Fucoidans are sulfated fucose-based polysaccharides that activate platelets and have pro- and anticoagulant effects; thus, they may have therapeutic value. In the present study, we show that 2 synthetic sulfated α-l-fucoside-pendant glycopolymers (with average monomeric units of 13 and 329) and natural fucoidans activate human platelets through a Src- and phosphatidylinositol 3-kinase (PI3K)-dependent and Syk-independent signaling cascade downstream of the platelet endothelial aggregation receptor 1 (PEAR1). Synthetic glycopolymers and natural fucoidan stimulate marked phosphorylation of PEAR1 and Akt, but not Syk. Platelet aggregation and Akt phosphorylation induced by natural fucoidan and synthetic glycopolymers are blocked by a monoclonal antibody to PEAR1. Direct binding of sulfated glycopolymers to epidermal like growth factor (EGF)-like repeat 13 of PEAR1 was shown by avidity-based extracellular protein interaction screen technology. In contrast, synthetic glycopolymers and natural fucoidans activate mouse platelets through a Src- and Syk-dependent pathway regulated by C-type lectin-like receptor 2 (CLEC-2) with only a minor role for PEAR1. Mouse platelets lacking the extracellular domain of GPIbα and human platelets treated with GPIbα-blocking antibodies display a reduced aggregation response to synthetic glycopolymers. We found that synthetic sulfated glycopolymers bind directly to GPIbα, substantiating that GPIbα facilitates the interaction of synthetic glycopolymers with CLEC-2 or PEAR1. Our results establish PEAR1 as the major signaling receptor for natural fucose-based polysaccharides and synthetic glycopolymers in human, but not in mouse, platelets. Sulfated α-l-fucoside-pendant glycopolymers are unique tools for further investigation of the physiological role of PEAR1 in platelets and beyond."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.org/dc/terms/identifier"doi:10.1182/bloodadvances.2018024950"xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Sun Y."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Watson S."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Eble J.A."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Haining E.J."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Rainger G.E."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Watson S.P."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Hoylaerts M.F."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Lindkvist M."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Ljungberg L.U."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Emsley J."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Barroso R."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Konradsson P."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Falker K."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Grenegard M."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Pahlsson P."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Criel M."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Kardeby C."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/author"Tengdelius M."xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/name"Blood Adv"xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/pages"275-287"xsd:string
http://purl.uniprot.org/citations/30700416http://purl.uniprot.org/core/title"Synthetic glycopolymers and natural fucoidans cause human platelet aggregation via PEAR1 and GPIbalpha."xsd:string
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