| http://purl.uniprot.org/citations/28028021 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28028021 | http://www.w3.org/2000/01/rdf-schema#comment | "Mitogen-activated protein kinases (MAPKs) are expressed in platelets and are activated downstream of physiological agonists. Pharmacological and genetic evidence indicate that MAPKs play a significant role in hemostasis and thrombosis, but it is not well understood how MAPKs are activated upon platelet stimulation. Here, we show that apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP3K family, is expressed in both human and murine platelets. ASK1 is rapidly and robustly activated upon platelet stimulation by physiological agonists. Disruption of Ask1 (Ask1-/- ) resulted in a marked functional defect in platelets. Ask1-/- platelets showed an impaired agonist-induced integrin αIIbβ3 activation and platelet aggregation. Although there was no difference in Ca2+ rise, platelet granule secretion and thromboxane A2 (TxA2) generation were significantly attenuated in Ask1-/- platelets. The defective granule secretion observed in Ask1-/- platelets was a consequence of impaired TxA2 generation. Biochemical studies showed that platelet agonists failed to activate p38 MAPK in Ask1-/- platelets. On the contrary, activation of c-Jun N-terminal kinases and extracellular signal-regulated kinase 1/2 MAPKs was augmented in Ask1-/- platelets. The defect in p38 MAPK results in failed phosphorylation of cPLA2 in Ask1-/- platelets and impaired platelet aggregate formation under flow. The absence of Ask1 renders mice defective in hemostasis as assessed by prolonged tail-bleeding times. Deletion of Ask1 also reduces thrombosis as assessed by delayed vessel occlusion of carotid artery after FeCl3-induced injury and protects against collagen/epinephrine-induced pulmonary thromboembolism. These results suggest that the platelet Ask1 plays an important role in regulation of hemostasis and thrombosis."xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2016-07-729780"xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/author | "Chen X."xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/author | "Patel P."xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/author | "Ichijo H."xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/author | "Naik M.U."xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/author | "Naik U.P."xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/author | "Neeves K.B."xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/author | "Golla K."xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/author | "Derstine R."xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/author | "Turaga R."xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/pages | "1197-1209"xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/title | "Ask1 regulates murine platelet granule secretion, thromboxane A2 generation, and thrombus formation."xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://purl.uniprot.org/core/volume | "129"xsd:string |
| http://purl.uniprot.org/citations/28028021 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28028021 |
| http://purl.uniprot.org/citations/28028021 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28028021 |
| http://purl.uniprot.org/uniprot/#_A0A1L1ST18-mappedCitation-28028021 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28028021 |
| http://purl.uniprot.org/uniprot/#_D3YVC4-mappedCitation-28028021 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28028021 |
| http://purl.uniprot.org/uniprot/#_D3Z5H1-mappedCitation-28028021 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28028021 |
| http://purl.uniprot.org/uniprot/#_A0A8V8TMH5-mappedCitation-28028021 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28028021 |
| http://purl.uniprot.org/uniprot/#_B4DF67-mappedCitation-28028021 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28028021 |
| http://purl.uniprot.org/uniprot/#_E9PWG9-mappedCitation-28028021 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28028021 |