| http://purl.uniprot.org/citations/15878855 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15878855 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15878855 | http://www.w3.org/2000/01/rdf-schema#comment | "The insulin-like growth factor-1 receptor (IGF-1R) plays important roles in physiological growth and aging as well as promoting several crucial functions in cancer cells. However, the molecular mechanisms involved in expression and down-regulation of IGF-1R are still poorly understood. Here we provide evidence that beta-arrestin, otherwise known to be involved in the regulation of G protein-coupled receptors, serves as an adaptor to bring the oncoprotein E3 ubiquitin ligase MDM2 to the IGF-1R. In this way, beta-arrestin acts as a crucial component in the ubiquitination and down-regulation of the receptor. Both MDM2 and beta-arrestin co-immunoprecipitated with the IGF-1R. The beta-arrestin isoform 1 appeared to be more strongly associated with the receptor than isoform 2, and in a molecular context it was 4-fold more efficient in inducing polyubiquitination of IGF-1R, a reaction that required the presence of beta-arrestin and MDM2. Ligand stimulation accelerated IGF-1R ubiquitination. In mouse P6 cells (overexpressing human IGF-1R) absence of beta-arrestin 1, but not of beta-arrestin 2, blocked ubiquitination of IGF-1R. Conversely, in the two studied human melanoma cell lines both beta-arrestin isoforms seemed to be involved in IGF-1R ubiquitination. However, because depletion of beta-arrestin 1 almost completely eliminated degradation, and IGF-1 induced down-regulation of the receptor in these cells, whereas beta-arrestin 2 only had a partial effect, beta-arrestin 1 seems to the more important isoform in affecting the expression of IGF-1R. To our knowledge this is the first study demonstrating a defined molecular role of beta-arrestin with direct relevance to cell growth and cancer."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m501129200"xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m501129200"xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Lefkowitz R.J."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Lefkowitz R.J."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Shenoy S.K."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Shenoy S.K."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Girnita A."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Girnita A."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Girnita L."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Girnita L."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Larsson O."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Larsson O."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Sehat B."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Sehat B."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Vasilcanu R."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/author | "Vasilcanu R."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/pages | "24412-24419"xsd:string |
| http://purl.uniprot.org/citations/15878855 | http://purl.uniprot.org/core/pages | "24412-24419"xsd:string |