| http://purl.uniprot.org/citations/33257569 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33257569 | http://www.w3.org/2000/01/rdf-schema#comment | "The three members of the endocrine-fibroblast growth factor (FGF) family, FGF19, 21, and 23 are circulating hormones that regulate critical metabolic processes. FGF23 stimulates the assembly of a signaling complex composed of α-Klotho (KLA) and FGF receptor (FGFR) resulting in kinase activation, regulation of phosphate homeostasis, and vitamin D levels. Here we report that the C-terminal tail of FGF23, a region responsible for KLA binding, contains two tandem repeats, repeat 1 (R1) and repeat 2 (R2) that function as two distinct ligands for KLA. FGF23 variants with a single KLA binding site, FGF23-R1, FGF23-R2, or FGF23-wild type (WT) with both R1 and R2, bind to KLA with similar binding affinity and stimulate FGFR1 activation and MAPK response. R2 is flanked by two cysteines that form a disulfide bridge in FGF23-WT; disulfide bridge formation in FGF23-WT is dispensable for KLA binding and for cell signaling via FGFRs. We show that FGF23-WT stimulates dimerization and activation of a chimeric receptor molecule composed of the extracellular domain of KLA fused to the cytoplasmic domain of FGFR and employ total internal reflection fluorescence microscopy to visualize individual KLA molecules on the cell surface. These experiments demonstrate that FGF23-WT can act as a bivalent ligand of KLA in the cell membrane. Finally, an engineered Fc-R2 protein acts as an FGF23 antagonist offering new pharmacological intervention for treating diseases caused by excessive FGF23 abundance or activity."xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.2018554117"xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/author | "Lee S."xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/author | "Li W."xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/author | "Suzuki Y."xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/author | "Schlessinger J."xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/author | "Lax I."xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/author | "Mohanty J."xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/author | "Tome F."xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/author | "An S.J."xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/author | "Kuzina E."xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/pages | "31800-31807"xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/title | "FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with alpha-Klotho."xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://purl.uniprot.org/core/volume | "117"xsd:string |
| http://purl.uniprot.org/citations/33257569 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/33257569 |
| http://purl.uniprot.org/citations/33257569 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/33257569 |
| http://purl.uniprot.org/uniprot/#_Q7Z4T2-mappedCitation-33257569 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33257569 |
| http://purl.uniprot.org/uniprot/#_Q9GZV9-mappedCitation-33257569 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33257569 |
| http://purl.uniprot.org/uniprot/Q9GZV9 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/33257569 |
| http://purl.uniprot.org/uniprot/Q7Z4T2 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/33257569 |