| http://purl.uniprot.org/citations/10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/10358158 | http://www.w3.org/2000/01/rdf-schema#comment | "Recent studies indicate that c-Cbl and its oncogenic variants can modulate the activity of protein tyrosine kinases. This finding is supported by studies showing that c-Cbl interacts directly with a negative regulatory tyrosine in ZAP-70, and that the levels of tyrosine-phosphorylated ZAP-70 and numerous other proteins are increased in TCR-stimulated thymocytes from c-Cbl-deficient mice. Here, we demonstrate that this enhanced phosphorylation of ZAP-70 and that of two substrates, LAT and SLP-76, is not due to altered protein levels but is the consequence of two separate events. First, we find increased expression of tyrosine-phosphorylated TCRzeta chain in c-Cbl-deficient thymocytes, which results in a higher level of zeta-chain-associated ZAP-70 that is initially accessible for activation. Thus, more ZAP-70 is activated and more of its substrates (LAT and SLP-76) become tyrosine-phosphorylated after TCR stimulation. However, an additional mechanism of ZAP-70 regulation is evident at a later time poststimulation. At this time, ZAP-70 from both normal and c-Cbl-/-thymocytes becomes hyperphosphorylated; however, only in normal thymocytes does this correlate with ZAP-70 down-regulation and a diminished ability to phosphorylate LAT and SLP-76. In contrast, c-Cbl-deficient thymocytes display altered phosphorylation kinetics, for which LAT phosphorylation is increased and SLP-76 phosphorylation is sustained. Thus, the ability to down-regulate the phosphorylation of two ZAP-70 substrates is impaired in c-Cbl-/-thymocytes. These findings provide evidence that c-Cbl is involved in the negative regulation of the phosphorylation of LAT and SLP-76 by ZAP-70."xsd:string |
| http://purl.uniprot.org/citations/10358158 | http://purl.uniprot.org/core/author | "Langdon W.Y."xsd:string |
| http://purl.uniprot.org/citations/10358158 | http://purl.uniprot.org/core/author | "Bowtell D.D."xsd:string |
| http://purl.uniprot.org/citations/10358158 | http://purl.uniprot.org/core/author | "Thien C.B."xsd:string |
| http://purl.uniprot.org/citations/10358158 | http://purl.uniprot.org/core/date | "1999"xsd:gYear |
| http://purl.uniprot.org/citations/10358158 | http://purl.uniprot.org/core/name | "J Immunol"xsd:string |
| http://purl.uniprot.org/citations/10358158 | http://purl.uniprot.org/core/pages | "7133-7139"xsd:string |
| http://purl.uniprot.org/citations/10358158 | http://purl.uniprot.org/core/title | "Perturbed regulation of ZAP-70 and sustained tyrosine phosphorylation of LAT and SLP-76 in c-Cbl-deficient thymocytes."xsd:string |
| http://purl.uniprot.org/citations/10358158 | http://purl.uniprot.org/core/volume | "162"xsd:string |
| http://purl.uniprot.org/citations/10358158 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/10358158 |
| http://purl.uniprot.org/citations/10358158 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/10358158 |
| http://purl.uniprot.org/uniprot/#_A0A087WQ05-mappedCitation-10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10358158 |
| http://purl.uniprot.org/uniprot/#_A0A0U1RP17-mappedCitation-10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10358158 |
| http://purl.uniprot.org/uniprot/#_A0A0U1RP47-mappedCitation-10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10358158 |
| http://purl.uniprot.org/uniprot/#_A0A0U1RP95-mappedCitation-10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10358158 |
| http://purl.uniprot.org/uniprot/#_A0A0U1RNF1-mappedCitation-10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10358158 |
| http://purl.uniprot.org/uniprot/#_E9Q696-mappedCitation-10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10358158 |
| http://purl.uniprot.org/uniprot/#_P70443-mappedCitation-10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10358158 |
| http://purl.uniprot.org/uniprot/#_A2MZG6-mappedCitation-10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10358158 |
| http://purl.uniprot.org/uniprot/#_A0A0X1KG61-mappedCitation-10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10358158 |
| http://purl.uniprot.org/uniprot/#_A0A0U1RQ85-mappedCitation-10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10358158 |
| http://purl.uniprot.org/uniprot/#_B1NE42-mappedCitation-10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10358158 |
| http://purl.uniprot.org/uniprot/#_B2KG65-mappedCitation-10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10358158 |
| http://purl.uniprot.org/uniprot/#_J3QMU3-mappedCitation-10358158 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10358158 |