| http://purl.uniprot.org/citations/26534964 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26534964 | http://www.w3.org/2000/01/rdf-schema#comment | "Signal regulatory protein α (SIRPα) is a membrane glycoprotein immunoreceptor abundant in cells of monocyte lineage. SIRPα ligation by a broadly expressed transmembrane protein, CD47, results in phosphorylation of the cytoplasmic immunoreceptor tyrosine-based inhibitory motifs, resulting in the inhibition of NF-κB signaling in macrophages. Here we observed that proteolysis of SIRPα during inflammation is regulated by a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), resulting in the generation of a membrane-associated cleavage fragment in both THP-1 monocytes and human lung epithelia. We mapped a charge-dependent putative cleavage site near the membrane-proximal domain necessary for ADAM10-mediated cleavage. In addition, a secondary proteolytic cleavage within the membrane-associated SIRPα fragment by γ-secretase was identified. Ectopic expression of a SIRPα mutant plasmid encoding a proteolytically resistant form in HeLa cells inhibited activation of the NF-κB pathway and suppressed STAT1 phosphorylation in response to TNFα to a greater extent than expression of wild-type SIRPα. Conversely, overexpression of plasmids encoding the proteolytically cleaved SIRPα fragments in cells resulted in enhanced STAT-1 and NF-κB pathway activation. Thus, the data suggest that combinatorial actions of ADAM10 and γ-secretase on SIRPα cleavage promote inflammatory signaling."xsd:string |
| http://purl.uniprot.org/citations/26534964 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m115.682914"xsd:string |
| http://purl.uniprot.org/citations/26534964 | http://purl.uniprot.org/core/author | "Londino J.D."xsd:string |
| http://purl.uniprot.org/citations/26534964 | http://purl.uniprot.org/core/author | "Mallampalli R.K."xsd:string |
| http://purl.uniprot.org/citations/26534964 | http://purl.uniprot.org/core/author | "Isenberg J.S."xsd:string |
| http://purl.uniprot.org/citations/26534964 | http://purl.uniprot.org/core/author | "Gulick D."xsd:string |
| http://purl.uniprot.org/citations/26534964 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26534964 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/26534964 | http://purl.uniprot.org/core/pages | "31113-31125"xsd:string |
| http://purl.uniprot.org/citations/26534964 | http://purl.uniprot.org/core/title | "Cleavage of Signal Regulatory Protein alpha (SIRPalpha) Enhances Inflammatory Signaling."xsd:string |
| http://purl.uniprot.org/citations/26534964 | http://purl.uniprot.org/core/volume | "290"xsd:string |
| http://purl.uniprot.org/citations/26534964 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26534964 |
| http://purl.uniprot.org/citations/26534964 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26534964 |
| http://purl.uniprot.org/uniprot/#_B4DP97-mappedCitation-26534964 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26534964 |
| http://purl.uniprot.org/uniprot/#_P78324-mappedCitation-26534964 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26534964 |
| http://purl.uniprot.org/uniprot/B4DP97 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/26534964 |
| http://purl.uniprot.org/uniprot/P78324 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/26534964 |