| http://purl.uniprot.org/citations/11110708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/11110708 | http://www.w3.org/2000/01/rdf-schema#comment | "More than half of anaplastic large-cell lymphomas (ALCLs) have a chromosomal translocation t(2;5) that leads to the expression of a hybrid protein composed of the nucleolar phosphoprotein nucleophosmin (NPM) and the anaplastic lymphoma kinase (ALK) that exhibits an unregulated tyrosine kinase activity. We have previously identified PLC-gamma as a crucial downstream signaling molecule of NPM-ALK that contributes to its mitogenic potential. Here, we show that NPM-ALK recruits the C-terminal SH2 domain of the phosphatidylinositol 3-kinase (PI 3kinase) p85 subunit. PI 3-kinase assays revealed that the kinase is activated by NPM-ALK in vivo, in turn activating PKB/Akt in NPM-ALK-expressing cells. The use of 2 specific PI 3-kinase inhibitors, wortmannin and LY294002, demonstrated the requirement of PI 3-kinase for the growth of NPM-ALK-transformed cell lines, as well as a cell line established from a patient with ALCL. Primary murine bone marrow retrovirally transduced with NPM-ALK showed a transformed phenotype that was reversible on treatment with PI 3-kinase inhibitors. Flow cytometric analysis revealed that wortmannin-treated NPM-ALK-transformed cell lines underwent apoptosis. Furthermore, apoptosis induced by overexpression of the proapoptotic molecule Bad could be partially blocked by the overexpression of NPM-ALK. Thus, NPM-ALK activates the antiapoptotic PI 3-kinase/Akt pathway, which likely contributes to the molecular pathogenesis of ALCL. (Blood. 2000;96:4319-4327)"xsd:string |
| http://purl.uniprot.org/citations/11110708 | http://purl.uniprot.org/core/author | "Bai R.Y."xsd:string |
| http://purl.uniprot.org/citations/11110708 | http://purl.uniprot.org/core/author | "Duyster J."xsd:string |
| http://purl.uniprot.org/citations/11110708 | http://purl.uniprot.org/core/author | "Morris S.W."xsd:string |
| http://purl.uniprot.org/citations/11110708 | http://purl.uniprot.org/core/author | "Peschel C."xsd:string |
| http://purl.uniprot.org/citations/11110708 | http://purl.uniprot.org/core/author | "Miething C."xsd:string |
| http://purl.uniprot.org/citations/11110708 | http://purl.uniprot.org/core/author | "Ouyang T."xsd:string |
| http://purl.uniprot.org/citations/11110708 | http://purl.uniprot.org/core/date | "2000"xsd:gYear |
| http://purl.uniprot.org/citations/11110708 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/11110708 | http://purl.uniprot.org/core/pages | "4319-4327"xsd:string |
| http://purl.uniprot.org/citations/11110708 | http://purl.uniprot.org/core/title | "Nucleophosmin-anaplastic lymphoma kinase associated with anaplastic large-cell lymphoma activates the phosphatidylinositol 3-kinase/Akt antiapoptotic signaling pathway."xsd:string |
| http://purl.uniprot.org/citations/11110708 | http://purl.uniprot.org/core/volume | "96"xsd:string |
| http://purl.uniprot.org/citations/11110708 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/11110708 |
| http://purl.uniprot.org/citations/11110708 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/11110708 |
| http://purl.uniprot.org/uniprot/#_Q14203-mappedCitation-11110708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11110708 |
| http://purl.uniprot.org/uniprot/#_P21741-mappedCitation-11110708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11110708 |
| http://purl.uniprot.org/uniprot/#_P27986-mappedCitation-11110708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11110708 |
| http://purl.uniprot.org/uniprot/#_P02751-mappedCitation-11110708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11110708 |
| http://purl.uniprot.org/uniprot/#_P42338-mappedCitation-11110708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11110708 |
| http://purl.uniprot.org/uniprot/#_O00459-mappedCitation-11110708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11110708 |
| http://purl.uniprot.org/uniprot/#_P06748-mappedCitation-11110708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11110708 |
| http://purl.uniprot.org/uniprot/#_Q00610-mappedCitation-11110708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11110708 |
| http://purl.uniprot.org/uniprot/#_P21246-mappedCitation-11110708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11110708 |
| http://purl.uniprot.org/uniprot/#_P33176-mappedCitation-11110708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11110708 |