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http://purl.uniprot.org/citations/28928125http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28928125http://www.w3.org/2000/01/rdf-schema#comment"Platelets, anucleated megakaryocyte (MK)-derived cells, play a major role in hemostasis and arterial thrombosis. Although protein kinase casein kinase 2 (CK2) is readily detected in MKs and platelets, the impact of CK2-dependent signaling on MK/platelet (patho-)physiology has remained elusive. The present study explored the impact of the CK2 regulatory β-subunit on platelet biogenesis and activation. MK/platelet-specific genetic deletion of CK2β (ck2β-/- ) in mice resulted in a significant macrothrombocytopenia and an increased extramedullar megakaryopoiesis with an enhanced proportion of premature platelets. Although platelet life span was only mildly affected, ck2β-/- MK displayed an abnormal microtubule structure with a drastically increased fragmentation within bone marrow and a significantly reduced proplatelet formation in vivo. In ck2β-/- platelets, tubulin polymerization was disrupted, resulting in an impaired thrombopoiesis and an abrogated inositol 1,4,5-triphosphate receptor-dependent intracellular calcium (Ca2+) release. Presumably due to a blunted increase in the concentration of cytosolic Ca2+, activation-dependent increases of α and dense-granule secretion and integrin αIIbβ3 activation, and aggregation were abrogated in ck2β-/- platelets. Accordingly, thrombus formation and stabilization under high arterial shear rates were significantly diminished, and thrombotic vascular occlusion in vivo was significantly blunted in ck2β-/- mice, accompanied by a slight prolongation of bleeding time. Following transient middle cerebral artery occlusion, ck2β-/- mice displayed significantly reduced cerebral infarct volumes, developed significantly less neurological deficits, and showed significantly better outcomes after ischemic stroke than ck2βfl/fl mice. The present observations reveal CK2β as a novel powerful regulator of thrombopoiesis, Ca2+-dependent platelet activation, and arterial thrombosis in vivo."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.org/dc/terms/identifier"doi:10.1182/blood-2017-05-784413"xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Lang F."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Nieswandt B."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Gawaz M."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Chatterjee M."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Schulze H."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Gonzalez Menendez I."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Buchou T."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Litchfield D.W."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Pleines I."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Quintanilla-Martinez L."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Salih H.R."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Stegner D."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Kleinschnitz C."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Borst O."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Munzer P."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Langhauser F."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Marklin M."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Geue S."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Geuss E."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Walker-Allgaier B."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Semeniak D."xsd:string
http://purl.uniprot.org/citations/28928125http://purl.uniprot.org/core/author"Aurbach K."xsd:string
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