| http://purl.uniprot.org/citations/21708940 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21708940 | http://www.w3.org/2000/01/rdf-schema#comment | "The IL-1β signaling cascade is initiated by the phosphorylation of IL-1β receptor-associated kinase-1 (IRAK-1), followed by its ubiquitination and degradation. This paper investigates the regulation of IRAK-1 degradation in primary hepatocytes and in HEK cells overexpressing the IL-1β receptor. We provide evidence that protein phosphatase 2A (PP2A) is a negative regulator of the phosphorylation, Lys(48)-linked ubiquitination, and degradation of IRAK-1. PP2A catalytic activity increased within 30 min of stimulation with IL-1β. siRNA against PP2A catalytic subunit (PP2Ac) or treatment with pharmacological inhibitor, okadaic acid, enhanced IRAK-1 Lys(48)-linked ubiquitination and degradation. Direct interaction between PP2Ac and IRAK-1 was observed, suggesting that IRAK-1 might be a PP2A substrate. The mechanisms of PP2A activation by IL-1β involved neutral sphingomyelinase-2 (NSMase-2) and an accumulation of ceramide. Overexpression of NSMase-2 delayed IRAK-1 degradation in a PP2A-dependent manner, whereas NSMase-2 silencing had the opposite effect. The addition of sphingomyelinase, ceramide, or a proteasome inhibitor all led to retention of IRAK-1 at the cell membrane and to increased JNK phosphorylation. This study suggests that NSMase-2- and PP2A-dependent regulation of IRAK-1 degradation is a novel mechanism to fine tune the magnitude of IL-1β response."xsd:string |
| http://purl.uniprot.org/citations/21708940 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m111.238030"xsd:string |
| http://purl.uniprot.org/citations/21708940 | http://purl.uniprot.org/core/author | "Giltiay N.V."xsd:string |
| http://purl.uniprot.org/citations/21708940 | http://purl.uniprot.org/core/author | "Karakashian A.A."xsd:string |
| http://purl.uniprot.org/citations/21708940 | http://purl.uniprot.org/core/author | "Nikolova-Karakashian M.N."xsd:string |
| http://purl.uniprot.org/citations/21708940 | http://purl.uniprot.org/core/author | "Dobierzewska A."xsd:string |
| http://purl.uniprot.org/citations/21708940 | http://purl.uniprot.org/core/author | "Sabapathi S."xsd:string |
| http://purl.uniprot.org/citations/21708940 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21708940 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/21708940 | http://purl.uniprot.org/core/pages | "32064-32073"xsd:string |
| http://purl.uniprot.org/citations/21708940 | http://purl.uniprot.org/core/title | "Protein phosphatase 2A and neutral sphingomyelinase 2 regulate IRAK-1 protein ubiquitination and degradation in response to interleukin-1beta."xsd:string |
| http://purl.uniprot.org/citations/21708940 | http://purl.uniprot.org/core/volume | "286"xsd:string |
| http://purl.uniprot.org/citations/21708940 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21708940 |
| http://purl.uniprot.org/citations/21708940 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21708940 |
| http://purl.uniprot.org/uniprot/#_D4A8L3-mappedCitation-21708940 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21708940 |
| http://purl.uniprot.org/uniprot/#_A6IYW6-mappedCitation-21708940 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21708940 |
| http://purl.uniprot.org/uniprot/#_A8K0T6-mappedCitation-21708940 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21708940 |
| http://purl.uniprot.org/uniprot/#_B7ZL84-mappedCitation-21708940 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21708940 |
| http://purl.uniprot.org/uniprot/#_C8CHW6-mappedCitation-21708940 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21708940 |
| http://purl.uniprot.org/uniprot/#_D6Q0F1-mappedCitation-21708940 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21708940 |
| http://purl.uniprot.org/uniprot/#_P51617-mappedCitation-21708940 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21708940 |
| http://purl.uniprot.org/uniprot/#_L8E7M9-mappedCitation-21708940 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21708940 |
| http://purl.uniprot.org/uniprot/#_Q1ZYL9-mappedCitation-21708940 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21708940 |
| http://purl.uniprot.org/uniprot/#_O35049-mappedCitation-21708940 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21708940 |