{"corpus_id":20697776,"paper_sha":"5258b445013c59131d0609aa5f489f56e913938b","doi":"10.1074/jbc.C500457200","arxiv_id":null,"pmid":16436388,"pmcid":"PMC2637204","mag_id":2164533721,"dblp_id":null,"acl_id":null,"title":"Regulation of Fibroblast Growth Factor-23 Signaling by Klotho*","year":2006,"publication_date":"2006-03-10","venue":"Journal of Biological Chemistry","journal":{"name":"Journal of Biological Chemistry","pages":"6120 - 6123","volume":"281"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":22,"citation_count":1317,"influential_citation_count":83,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Cell Line","mj":false,"ui":"D002460"},{"d":"Fibroblast Growth Factor-23","mj":false,"ui":"D000089703"},{"d":"Fibroblast Growth Factors","mj":false,"qs":[{"q":"deficiency","mj":false,"ui":"Q000172"},{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D005346"},{"d":"Glucuronidase","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D005966"},{"d":"HeLa Cells","mj":false,"ui":"D006367"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Klotho Proteins","mj":false,"ui":"D000090265"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Mice, Knockout","mj":false,"ui":"D018345"},{"d":"PC12 Cells","mj":false,"ui":"D016716"},{"d":"Rats","mj":false,"ui":"D051381"},{"d":"Receptors, Fibroblast Growth Factor","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D017468"},{"d":"Signal Transduction","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D015398"}],"chemicals":[{"n":"FGF23 protein, human","ui":"C000717427","reg":"0"},{"n":"Fgf23 protein, mouse","ui":"C000717428","reg":"0"},{"n":"Receptors, Fibroblast Growth Factor","ui":"D017468","reg":"0"},{"n":"Fibroblast Growth Factors","ui":"D005346","reg":"62031-54-3"},{"n":"Fibroblast Growth Factor-23","ui":"D000089703","reg":"7Q7P4S7RRE"},{"n":"Glucuronidase","ui":"D005966","reg":"EC 3.2.1.31"},{"n":"Klotho Proteins","ui":"D000090265","reg":"EC 3.2.1.31"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"http://www.jbc.org/article/S0021925819579649/pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/5258b445013c59131d0609aa5f489f56e913938b","s2_open_access_license":"CCBY","s2_open_access_status":"HYBRID","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"The aging suppressor gene Klotho encodes a single-pass transmembrane protein. Klotho-deficient mice exhibit a variety of aging-like phenotypes, many of which are similar to those observed in fibroblast growth factor-23 (FGF23)-deficient mice. To test the possibility that Klotho and FGF23 may function in a common signal transduction pathway(s), we investigated whether Klotho is involved in FGF signaling. Here we show that Klotho protein directly binds to multiple FGF receptors (FGFRs). The Klotho-FGFR complex binds to FGF23 with higher affinity than FGFR or Klotho alone. In addition, Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. Thus, Klotho functions as a cofactor essential for activation of FGF signaling by FGF23.","claims":[{"public_id":"cl_735901a745d1a110713aed21d377b427","status":"active","text":"Klotho enhances fibroblast growth factor-23-induced phosphorylation of fibroblast growth factor receptor substrate and ERK in various cell types.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_735901a745d1a110713aed21d377b427"},{"public_id":"cl_c0b2dca36c239261cf47882cadeb0193","status":"active","text":"Klotho functions as a cofactor essential for activation of fibroblast growth factor signaling by fibroblast growth factor-23.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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