| http://purl.uniprot.org/citations/22787435 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22787435 | http://www.w3.org/2000/01/rdf-schema#comment | "Suppressors of cytokine signaling 1 and 3 (SOCS-1 and SOCS-3) are inhibitors of the Janus tyrosine kinase (JAK)/signal transducers and activators of transcription (STAT) pathway and function in a negative feedback loop during cytokine signaling. Abl transformation is associated with constitutive activation of JAK/STAT-dependent signaling. However, the mechanism by which Abl oncoproteins bypass SOCS inhibitory regulation remains poorly defined. Here, we demonstrate that coexpression of Bcr-Abl with SOCS-1 or SOCS-3 results in tyrosine phosphorylation of these SOCS proteins. Interestingly, SOCS-1 is highly tyrosine phosphorylated in one of five primary chronic myelogenous leukemia samples. Bcr-Abl-dependent tyrosine phosphorylation of SOCS-1 and SOCS-3 occurs mainly on Tyr 155 and Tyr 204 residues of SOCS-1 and on Tyr 221 residue of SOCS-3. We observed that phosphorylation of these SOCS proteins was associated with their binding to Bcr-Abl. Bcr-Abl-dependent phosphorylation of SOCS-1 and SOCS-3 diminished their inhibitory effects on the activation of JAK and STAT5 and thereby enhanced JAK/STAT5 signaling. Strikingly, disrupting the tyrosine phosphorylation of SOCS-1 or SOCS-3 impaired the expression of Bcl-X(L) protein and sensitized K562 leukemic cells to undergo apoptosis. Moreover, selective mutation of tyrosine phosphorylation sites of SOCS-1 or SOCS-3 significantly blocked Bcr-Abl-mediated tumorigenesis in nude mice and inhibited Bcr-Abl-mediated murine bone marrow transformation. Together, these results reveal a mechanism of how Bcr-Abl may overcome SOCS-1 and SOCS-3 inhibition to constitutively activate the JAK/STAT-dependent signaling, and suggest that Bcr-Abl may critically requires tyrosine phosphorylation of SOCS-1 and SOCS-3 to mediate tumorigenesis when these SOCS proteins are present in cells."xsd:string |
| http://purl.uniprot.org/citations/22787435 | http://purl.org/dc/terms/identifier | "doi:10.1596/neo.12230"xsd:string |
| http://purl.uniprot.org/citations/22787435 | http://purl.uniprot.org/core/author | "Chen K."xsd:string |
| http://purl.uniprot.org/citations/22787435 | http://purl.uniprot.org/core/author | "Qiu X."xsd:string |
| http://purl.uniprot.org/citations/22787435 | http://purl.uniprot.org/core/author | "Guo G."xsd:string |
| http://purl.uniprot.org/citations/22787435 | http://purl.uniprot.org/core/author | "Druker B.J."xsd:string |
| http://purl.uniprot.org/citations/22787435 | http://purl.uniprot.org/core/author | "Chen J.L."xsd:string |
| http://purl.uniprot.org/citations/22787435 | http://purl.uniprot.org/core/author | "Rothman P.B."xsd:string |
| http://purl.uniprot.org/citations/22787435 | http://purl.uniprot.org/core/author | "Kashiwada M."xsd:string |
| http://purl.uniprot.org/citations/22787435 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22787435 | http://purl.uniprot.org/core/name | "Neoplasia"xsd:string |
| http://purl.uniprot.org/citations/22787435 | http://purl.uniprot.org/core/pages | "547-558"xsd:string |
| http://purl.uniprot.org/citations/22787435 | http://purl.uniprot.org/core/title | "A requirement for SOCS-1 and SOCS-3 phosphorylation in Bcr-Abl-induced tumorigenesis."xsd:string |
| http://purl.uniprot.org/citations/22787435 | http://purl.uniprot.org/core/volume | "14"xsd:string |
| http://purl.uniprot.org/citations/22787435 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22787435 |
| http://purl.uniprot.org/citations/22787435 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22787435 |
| http://purl.uniprot.org/uniprot/#_A0A023PX70-mappedCitation-22787435 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22787435 |
| http://purl.uniprot.org/uniprot/#_A0A510LHF0-mappedCitation-22787435 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22787435 |
| http://purl.uniprot.org/uniprot/#_A0A510LHH1-mappedCitation-22787435 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22787435 |
| http://purl.uniprot.org/uniprot/#_A0A510LIH5-mappedCitation-22787435 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22787435 |
| http://purl.uniprot.org/uniprot/#_A0A2Z5DI15-mappedCitation-22787435 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22787435 |
| http://purl.uniprot.org/uniprot/#_A0A2X0SFQ7-mappedCitation-22787435 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22787435 |
| http://purl.uniprot.org/uniprot/#_A0A346G3H8-mappedCitation-22787435 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22787435 |
| http://purl.uniprot.org/uniprot/#_A9UEZ4-mappedCitation-22787435 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22787435 |