| http://purl.uniprot.org/citations/15576456 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15576456 | http://www.w3.org/2000/01/rdf-schema#comment | "We have previously described the phenotype resulting from a missense mutation in the IGF-I gene, which leads to expression of IGF-I with a methionine instead of a valine at position 44 (Val44Met IGF-I). This mutation caused severe growth and mental retardation as well as deafness evident at birth and growth retardation in childhood, but is relatively well tolerated in adulthood. We have conducted a biochemical and structural analysis of Val44Met IGF-I to provide a molecular basis for the phenotype observed. Val44Met IGF-I exhibits a 90-fold decrease in type 1 IGF receptor (IGF-1R) binding compared with wild-type human IGF-I and only poorly stimulates autophosphorylation of the IGF-1R. The ability of Val44Met IGF-I to signal via the extracellular signal-regulated kinase 1/2 and Akt/protein kinase B pathways and to stimulate DNA synthesis is correspondingly poorer. Binding or activation of both insulin receptor isoforms is not detectable even at micromolar concentrations. However, Val44Met IGF-I binds IGF-binding protein-2 (IGFBP-2), IGFBP-3, and IGFBP-6 with equal affinity to IGF-I, suggesting the maintenance of overall structure, particularly in the IGFBP binding domain. Structural analysis by nuclear magnetic resonance confirms retention of near-native structure with only local side-chain disruptions despite the significant loss of function. To our knowledge, our results provide the first structural study of a naturally occurring mutant human IGF-I associated with growth and developmental abnormalities and identifies Val44 as an essential residue involved in the IGF-IGF-1R interaction."xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.org/dc/terms/identifier | "doi:10.1210/me.2004-0409"xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/author | "Wang C.C."xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/author | "Wallace J.C."xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/author | "Norton R.S."xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/author | "Wit J.M."xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/author | "van Duyvenvoorde H."xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/author | "Karperien M."xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/author | "Forbes B.E."xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/author | "Denley A."xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/author | "McNeil K.A."xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/author | "Walenkamp M.J."xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/name | "Mol Endocrinol"xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/pages | "711-721"xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/title | "Structural and functional characteristics of the Val44Met insulin-like growth factor I missense mutation: correlation with effects on growth and development."xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://purl.uniprot.org/core/volume | "19"xsd:string |
| http://purl.uniprot.org/citations/15576456 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15576456 |
| http://purl.uniprot.org/citations/15576456 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15576456 |
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| http://purl.uniprot.org/uniprot/#_Q13429-mappedCitation-15576456 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15576456 |
| http://purl.uniprot.org/uniprot/#_P05019-mappedCitation-15576456 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15576456 |
| http://purl.uniprot.org/uniprot/#_Q5U743-mappedCitation-15576456 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15576456 |
| http://purl.uniprot.org/uniprot/#_Q6LD41-mappedCitation-15576456 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15576456 |