| http://purl.uniprot.org/citations/25287889 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25287889 | http://www.w3.org/2000/01/rdf-schema#comment | "Zeta-chain associated protein of 70 kDa (ZAP-70) and spleen tyrosine kinase (Syk) are non-receptor tyrosine kinases that are essential for T-cell and B-cell antigen receptor signalling respectively. They are recruited, via their tandem-SH2 (Src-homology domain 2) domains, to doubly phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) on invariant chains of immune antigen receptors. Because of their critical roles in immune signalling, ZAP-70 and Syk are targets for the development of drugs for autoimmune diseases. We show that three thiol-reactive small molecules can prevent the tandem-SH2 domains of ZAP-70 and Syk from binding to phosphorylated ITAMs. We identify a specific cysteine residue in the phosphotyrosine-binding pocket of each protein (Cys39 in ZAP-70, Cys206 in Syk) that is necessary for inhibition by two of these compounds. We also find that ITAM binding to ZAP-70 and Syk is sensitive to the presence of H2O2 and these two cysteine residues are also necessary for inhibition by H2O2. Our findings suggest a mechanism by which the reactive oxygen species generated during responses to antigen could attenuate signalling through these kinases and may also inform the development of ZAP-70 and Syk inhibitors that bind covalently to their SH2 domains."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.org/dc/terms/identifier | "doi:10.1042/bj20140793"xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/author | "Kuriyan J."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/author | "Yan Q."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/author | "Weiss A."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/author | "Barros T."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/author | "Wilson C.G."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/author | "Arkin M.R."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/author | "Visperas P.R."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/author | "Winger J.A."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/author | "Shah N.H."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/author | "Tao A."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/author | "Aum D.J."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/author | "Horton T.M."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/name | "Biochem J"xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/pages | "149-161"xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/title | "Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 domains of ZAP-70 and Syk can block phosphopeptide binding."xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://purl.uniprot.org/core/volume | "465"xsd:string |
| http://purl.uniprot.org/citations/25287889 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25287889 |
| http://purl.uniprot.org/citations/25287889 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25287889 |
| http://purl.uniprot.org/uniprot/#_A8K4G2-mappedCitation-25287889 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25287889 |
| http://purl.uniprot.org/uniprot/#_B3KQJ1-mappedCitation-25287889 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25287889 |
| http://purl.uniprot.org/uniprot/#_C3W980-mappedCitation-25287889 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25287889 |