| http://purl.uniprot.org/citations/19578119 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19578119 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19578119 | http://www.w3.org/2000/01/rdf-schema#comment | "It has been proposed that ligand occupancy of integrin alphavbeta3 with extracellular matrix ligands (e.g. vitronectin) plays a critical role in insulin-like growth factor-1 (IGF-1) signaling. We found that expression of alphavbeta3 enhanced IGF-1-induced proliferation of Chinese hamster ovary cells in serum-free conditions (in the absence of vitronectin). We hypothesized that the direct integrin binding to IGF-1 may play a role in IGF-1 signaling. We demonstrated that alphavbeta3 specifically and directly bound to IGF-1 in cell adhesion, enzyme-linked immunosorbent assay-type binding, and surface plasmon resonance studies. We localized the amino acid residues of IGF-1 that are critical for integrin binding by docking simulation and mutagenesis. We found that mutating two Arg residues at positions 36 and 37 in the C-domain of IGF-1 to Glu (the R36E/R37E mutation) effectively reduced integrin binding. Interestingly, although the mutant still bound to IGF1R, it was defective in inducing IGF1R phosphorylation, AKT and ERK1/2 activation, and cell proliferation. Furthermore wild type IGF-1 mediated co-precipitation of alphavbeta3 and IGF1R, whereas the R36E/R37E mutant did not, suggesting that IGF-1 mediates the interaction between alphavbeta3 and IGF1R. These results suggest that the direct binding to IGF-1 to integrin alphavbeta3 plays a role in IGF-1 signaling through ternary complex formation (alphavbeta3-IGF-IGF1R), and integrin-IGF-1 interaction is a novel target for drug discovery."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.013201"xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.013201"xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Takada Y."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Takada Y."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Wu C.Y."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Wu C.Y."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Yamaji S."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Yamaji S."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Lam K.S."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Lam K.S."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Liu F.T."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Liu F.T."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Takada Y.K."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Takada Y.K."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Ieguchi K."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Ieguchi K."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Saegusa J."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/author | "Saegusa J."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/19578119 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |