http://purl.uniprot.org/citations/24496246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/24496246 | http://www.w3.org/2000/01/rdf-schema#comment | "Background/aimsThe protein kinase Akt2/PKBβ is a known regulator of macrophage and dendritic cell (DC) migration. The mechanisms linking Akt2 activity to migration remained, however, elusive. DC migration is governed by Ca(2+) signaling. We thus explored whether Akt2 regulates DC Ca(2+) signaling.MethodsDCs were derived from bone marrow of Akt2-deficient mice (akt2(-/-)) and their wild type littermates (akt2(+/+)). DC maturation was induced by lipopolysaccharides (LPS) and evaluated by flow cytometry. Cytosolic Ca(2+) concentration was determined by Fura-2 fluorescence, channel activity by whole cell recording, transcript levels by RT-PCR, migration utilizing transwells.ResultsUpon maturation, chemokine CCL21 stimulated migration of akt2(+/+) but not akt2(-/-) DCs. CCL21-induced increase in cytosolic Ca(2+) concentration, thapsigargin-induced release of Ca(2+) from intracellular stores with subsequent store-operated Ca(2+) entry (SOCE), ATP-induced inositol 1,4,5-trisphosphate (IP3)-dependent Ca(2+) release as well as Ca(2+) release-activated Ca(2+) (CRAC) channel activity were all significantly lower in mature akt2(-/-) than in mature akt2(+/+) DCs. Transcript levels of IP3 receptor IP3R2 and of IP3R2 regulating transcription factor ETS1 were significantly higher in akt2(+/+) than in akt2(-/-) DCs prior to maturation and were upregulated by LPS stimulation (1h) in akt2(+/+) and to a lower extent in akt2(-/-) DCs. Following maturation, protein abundance of IP3R2 and ETS1 were similarly higher in akt2(+/+) than in akt2(-/-) DCs. The IP3R inhibitor Xestospongin C significantly decreased CCL21-induced migration of akt2(+/+)DCs and abrogated the differences between genotypes. Finally, knock-down of ETS1 with siRNA decreased IP3R2 mRNA abundance, thapsigargin- and ATP-induced Ca(2+) release, SOCE and CRAC channel activation, as well as DC migration.ConclusionAkt2 upregulates DC migration at least in part by ETS1-dependent stimulation of IP3R2 transcription."xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.org/dc/terms/identifier | "doi:10.1159/000356664"xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/author | "Yan J."xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/author | "Yang W."xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/author | "Lang F."xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/author | "Schmid E."xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/author | "Russo A."xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/author | "Shumilina E."xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/author | "Nurbaeva M.K."xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/author | "Szteyn K."xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/author | "Faggio C."xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/author | "Almilaji A."xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/name | "Cell Physiol Biochem"xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/pages | "222-236"xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/title | "Akt2- and ETS1-dependent IP3 receptor 2 expression in dendritic cell migration."xsd:string |
http://purl.uniprot.org/citations/24496246 | http://purl.uniprot.org/core/volume | "33"xsd:string |
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