| http://purl.uniprot.org/citations/15205474 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15205474 | http://www.w3.org/2000/01/rdf-schema#comment | "The insulin receptor (IR) lacking the alternatively spliced exon 11 (IR-A) is preferentially expressed in fetal and cancer cells. The IR-A has been identified as a high-affinity receptor for insulin and IGF-II but not IGF-I, which it binds with substantially lower affinity. Several cancer cell types that express the IR-A also overexpress IGF-II, suggesting a possible autocrine proliferative loop. To determine the regions of IGF-I and IGF-II responsible for this differential affinity, chimeras were made where the C and D domains were exchanged between IGF-I and IGF-II either singly or together. The abilities of these chimeras to bind to, and activate, the IR-A were investigated. We also investigated the ability of these chimeras to bind and activate the IR exon 11+ isoform (IR-B) and as a positive control, the IGF-I receptor (IGF-1R). We show that the C domain and, to a lesser extent, the D domains represent the principal determinants of the binding differences between IGF-I and IGF-II to IR-A. The C and D domains of IGF-II promote higher affinity binding to the IR-A than the equivalent domains of IGF-I, resulting in an affinity close to that of insulin for the IR-A. The C and D domains also regulate the IR-B binding specificity of the IGFs in a similar manner, although the level of binding for all IGF ligands to IR-B is lower than to IR-A. In contrast, the C and D domains of IGF-I allow higher affinity binding to the IGF-1R than the analogous domains of IGF-II. Activation of IGF-1R by the chimeras reflected their binding affinities whereas the phosphorylation of the two IR isoforms was more complex."xsd:string |
| http://purl.uniprot.org/citations/15205474 | http://purl.org/dc/terms/identifier | "doi:10.1210/me.2004-0183"xsd:string |
| http://purl.uniprot.org/citations/15205474 | http://purl.uniprot.org/core/author | "Wallace J.C."xsd:string |
| http://purl.uniprot.org/citations/15205474 | http://purl.uniprot.org/core/author | "Booker G.W."xsd:string |
| http://purl.uniprot.org/citations/15205474 | http://purl.uniprot.org/core/author | "Ward C.W."xsd:string |
| http://purl.uniprot.org/citations/15205474 | http://purl.uniprot.org/core/author | "Forbes B.E."xsd:string |
| http://purl.uniprot.org/citations/15205474 | http://purl.uniprot.org/core/author | "Denley A."xsd:string |
| http://purl.uniprot.org/citations/15205474 | http://purl.uniprot.org/core/author | "Cosgrove L.J."xsd:string |
| http://purl.uniprot.org/citations/15205474 | http://purl.uniprot.org/core/author | "Bonython E.R."xsd:string |
| http://purl.uniprot.org/citations/15205474 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/15205474 | http://purl.uniprot.org/core/name | "Mol Endocrinol"xsd:string |
| http://purl.uniprot.org/citations/15205474 | http://purl.uniprot.org/core/pages | "2502-2512"xsd:string |
| http://purl.uniprot.org/citations/15205474 | http://purl.uniprot.org/core/title | "Structural determinants for high-affinity binding of insulin-like growth factor II to insulin receptor (IR)-A, the exon 11 minus isoform of the IR."xsd:string |
| http://purl.uniprot.org/citations/15205474 | http://purl.uniprot.org/core/volume | "18"xsd:string |
| http://purl.uniprot.org/citations/15205474 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15205474 |
| http://purl.uniprot.org/citations/15205474 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15205474 |
| http://purl.uniprot.org/uniprot/#_A0A1U9WZ84-mappedCitation-15205474 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15205474 |
| http://purl.uniprot.org/uniprot/#_B0FJM0-mappedCitation-15205474 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15205474 |
| http://purl.uniprot.org/uniprot/#_A4ZPI1-mappedCitation-15205474 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15205474 |
| http://purl.uniprot.org/uniprot/#_A4ZPI2-mappedCitation-15205474 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15205474 |
| http://purl.uniprot.org/uniprot/#_A4ZPI3-mappedCitation-15205474 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15205474 |
| http://purl.uniprot.org/uniprot/#_B4DTR7-mappedCitation-15205474 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15205474 |
| http://purl.uniprot.org/uniprot/#_A1DR88-mappedCitation-15205474 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15205474 |
| http://purl.uniprot.org/uniprot/#_A4ZPI4-mappedCitation-15205474 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15205474 |