| http://purl.uniprot.org/citations/28163304 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28163304 | http://www.w3.org/2000/01/rdf-schema#comment | "Diacylglycerol kinase (DGK)-mediated consumption of the diacylglycerol (DAG) generated in response to antigen recognition is an important mechanism to limit T-cell function. Targeting DGK activity presents new opportunities for therapeutic manipulation of the immune response, but assessment of individual DGK functions is complex. T cells express two DGK isoforms, DGKα and DGKζ, and there are no isoform-specific inhibitors. Here we used short interfering RNA-mediated gene silencing in human T cells and DGKα- and DGKζ-deficient mice to define DGK isoform-specific regulation of key signaling pathways during T-cell activation. Our results identify DGKζ as the predominant brake on basal/tonic conditions as well as on downstream T-cell receptor/co-stimulatory signals. DGKζ silencing triggers basal RasGTP activation and facilitates enhanced membrane stability of protein kinase C alpha as well as increased activity of AGC kinases. Downstream of T-cell receptor/co-stimulation, DGKζ silencing results in enhanced and maintained recruitment of PKC theta to the membrane, as well as phosphoinositide-dependent protein kinase-1 activation and scaffolding functions. Our studies identify a previously unrecognized DGKζ contribution as a negative regulator of the crosstalk between phospholipase C-gamma- and phosphoinositide 3-kinase-regulated pathways. This DGKζ input helps to explain previous observations in DGK-deficient mice and suggests that the development of isoform-specific DGK inhibitors is of great interest for the manipulation of distinct aspects of T-cell responses."xsd:string |
| http://purl.uniprot.org/citations/28163304 | http://purl.org/dc/terms/identifier | "doi:10.1038/icb.2017.7"xsd:string |
| http://purl.uniprot.org/citations/28163304 | http://purl.uniprot.org/core/author | "Merida I."xsd:string |
| http://purl.uniprot.org/citations/28163304 | http://purl.uniprot.org/core/author | "Avila-Flores A."xsd:string |
| http://purl.uniprot.org/citations/28163304 | http://purl.uniprot.org/core/author | "Andrada E."xsd:string |
| http://purl.uniprot.org/citations/28163304 | http://purl.uniprot.org/core/author | "Soutar D."xsd:string |
| http://purl.uniprot.org/citations/28163304 | http://purl.uniprot.org/core/author | "Arranz-Nicolas J."xsd:string |
| http://purl.uniprot.org/citations/28163304 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28163304 | http://purl.uniprot.org/core/name | "Immunol Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/28163304 | http://purl.uniprot.org/core/pages | "549-563"xsd:string |
| http://purl.uniprot.org/citations/28163304 | http://purl.uniprot.org/core/title | "Predominant contribution of DGKzeta over DGKalpha in the control of PKC/PDK-1-regulated functions in T cells."xsd:string |
| http://purl.uniprot.org/citations/28163304 | http://purl.uniprot.org/core/volume | "95"xsd:string |
| http://purl.uniprot.org/citations/28163304 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28163304 |
| http://purl.uniprot.org/citations/28163304 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28163304 |
| http://purl.uniprot.org/uniprot/#_A0A668KL90-mappedCitation-28163304 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28163304 |
| http://purl.uniprot.org/uniprot/#_A2AHJ7-mappedCitation-28163304 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28163304 |
| http://purl.uniprot.org/uniprot/#_A2AHK0-mappedCitation-28163304 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28163304 |
| http://purl.uniprot.org/uniprot/#_Q05DE1-mappedCitation-28163304 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28163304 |
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| http://purl.uniprot.org/uniprot/#_Q91YS0-mappedCitation-28163304 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28163304 |
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| http://purl.uniprot.org/uniprot/Q05DE1 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28163304 |
| http://purl.uniprot.org/uniprot/A2AHJ7 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28163304 |