| http://purl.uniprot.org/citations/23125415 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23125415 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23125415 | http://www.w3.org/2000/01/rdf-schema#comment | "The membrane-bound chemokine fractalkine (FKN, CX3CL1) on endothelial cells plays a role in leukocyte trafficking. The chemokine domain (FKN-CD) is sufficient for inducing FKN signaling (e.g., integrin activation), and FKN-CD binds to its receptor CX3CR1 on leukocytes. Whereas previous studies suggest that FKN-CD does not directly bind to integrins, our docking simulation studies predicted that FKN-CD directly interacts with integrin α(v)β(3). Consistent with this prediction, we demonstrated that FKN-CD directly bound to α(v)β(3) and α(4)β(1) at a very high affinity (K(D) of 3.0 × 10(-10) M to α(v)β(3) in 1 mM Mn(2+)). Also, membrane-bound FKN bound to integrins α(v)β(3) and α(4)β(1), suggesting that the FKN-CD/integrin interaction is biologically relevant. The binding site for FKN-CD in α(v)β(3) was similar to those for other known α(v)β(3) ligands. Wild-type FKN-CD induced coprecipitation of integrins and CX3CR1 in U937 cells, suggesting that FKN-CD induces ternary complex formation (CX3CR1, FKN-CD, and integrin). Based on the docking model, we generated an integrin-binding defective FKN-CD mutant (the K36E/R37E mutant). K36E/R37E was defective in ternary complex formation and integrin activation, whereas K36E/R37E still bound to CX3CR1. These results suggest that FKN-CD binding to CX3CR1 is not sufficient for FKN signaling, and that FKN-CD binding to integrins as coreceptors and the resulting ternary complex formation are required for FKN signaling. Notably, excess K36E/R37E suppressed integrin activation induced by wild-type FKN-CD and effectively suppressed leukocyte infiltration in thioglycollate-induced peritonitis. These findings suggest that K36E/R37E acts as a dominant-negative CX3CR1 antagonist and that FKN-CD/integrin interaction is a novel therapeutic target in inflammatory diseases."xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1200889"xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1200889"xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/author | "Fujita M."xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/author | "Fujita M."xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/author | "Takada Y."xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/author | "Takada Y."xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/author | "Takada Y.K."xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/author | "Takada Y.K."xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/name | "J. Immunol."xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/name | "J. Immunol."xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/pages | "5809-5819"xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/pages | "5809-5819"xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/title | "Integrins alphavbeta3 and alpha4beta1 act as coreceptors for fractalkine, and the integrin-binding defective mutant of fractalkine is an antagonist of CX3CR1."xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/title | "Integrins alphavbeta3 and alpha4beta1 act as coreceptors for fractalkine, and the integrin-binding defective mutant of fractalkine is an antagonist of CX3CR1."xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/volume | "189"xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://purl.uniprot.org/core/volume | "189"xsd:string |
| http://purl.uniprot.org/citations/23125415 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23125415 |
| http://purl.uniprot.org/citations/23125415 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23125415 |
| http://purl.uniprot.org/citations/23125415 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23125415 |
| http://purl.uniprot.org/citations/23125415 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23125415 |