http://purl.uniprot.org/citations/25645675 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/25645675 | http://www.w3.org/2000/01/rdf-schema#comment | "Prostaglandin E2 (PGE2 ) protects against allergic responses via binding to prostanoid receptor EP4, which inhibits eosinophil migration in a PI3K/PKC-dependent fashion. The phosphoinositide-dependent protein kinase 1 (PDK1) is known to act as a downstream effector in PI3K signaling and has been implicated in the regulation of neutrophil migration. Thus, here we elucidate whether PDK1 mediates inhibitory effects of E-type prostanoid receptor 4 (EP4) receptors on eosinophil function. Therefore, eosinophils were isolated from human peripheral blood or differentiated from mouse BM. PDK1 signaling was investigated in shape change, chemotaxis, CD11b, respiratory burst, and Ca(2+) mobilization assays. The specific PDK1 inhibitors BX-912 and GSK2334470 prevented the inhibition by prostaglandin E2 and the EP4 agonist ONO-AE1-329. Depending on the cellular function, PDK1 seemed to act through PI3K-dependent or PI3K-independent mechanisms. Stimulation of EP4 receptors caused PDK1 phosphorylation at Ser396 and induced PI3K-dependent nuclear translocation of PDK1. EP4-induced inhibition of shape change and chemotaxis was effectively reversed by the Akt inhibitor triciribine. In support of this finding, ONO-AE1-329 induced a PI3K/PDK1-dependent increase in Akt phosphorylation. In conclusion, our data illustrate a critical role for PDK1 in transducing inhibitory signals on eosinophil effector function. Thus, our results suggest that PDK1 might serve as a novel therapeutic target in diseases involving eosinophilic inflammation."xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.org/dc/terms/identifier | "doi:10.1002/eji.201445196"xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/author | "Hammer A."xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/author | "Parzmair G.P."xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/author | "Schuligoi R."xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/author | "Heinemann A."xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/author | "Sturm G.J."xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/author | "Lippe I.T."xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/author | "Sturm E.M."xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/author | "Radnai B."xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/author | "Frei R.B."xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/name | "Eur J Immunol"xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/pages | "1548-1559"xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/title | "Phosphoinositide-dependent protein kinase 1 (PDK1) mediates potent inhibitory effects on eosinophils."xsd:string |
http://purl.uniprot.org/citations/25645675 | http://purl.uniprot.org/core/volume | "45"xsd:string |
http://purl.uniprot.org/citations/25645675 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25645675 |
http://purl.uniprot.org/citations/25645675 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25645675 |
http://purl.uniprot.org/uniprot/#_F2Z3V6-mappedCitation-25645675 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25645675 |
http://purl.uniprot.org/uniprot/#_B4DF26-mappedCitation-25645675 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25645675 |
http://purl.uniprot.org/uniprot/#_F2Z3X6-mappedCitation-25645675 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25645675 |
http://purl.uniprot.org/uniprot/#_F2Z3X9-mappedCitation-25645675 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25645675 |
http://purl.uniprot.org/uniprot/#_F2Z3Z9-mappedCitation-25645675 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25645675 |
http://purl.uniprot.org/uniprot/#_F2Z400-mappedCitation-25645675 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25645675 |