{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:59:12Z","timestamp":1788580752481,"version":"build-2803163510"},"reference-count":69,"publisher":"American Society for Clinical Investigation","issue":"17","funder":[{"name":"NIH","award":["R01DK073911,5K08AR067285,R01DK116716,R01AR05965,R01DE13686,P30AR066261"],"award-info":[{"award-number":["R01DK073911,5K08AR067285,R01DK116716,R01AR05965,R01DE13686,P30AR066261"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,5]]},"abstract":"<jats:p>\n                    Dysregulated actions of bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23) result in several inherited diseases, such as X-linked hypophosphatemia (XLH), and contribute substantially to the mortality in kidney failure. Mechanisms governing FGF23 production are poorly defined. We herein found that ablation of the G\n                    <jats:sub>q\/11<\/jats:sub>\n                    \u03b1\u2013like, extralarge G\u03b1 subunit (XL\u03b1s), a product of\n                    <jats:italic>GNAS<\/jats:italic>\n                    , exhibits FGF23 deficiency and hyperphosphatemia in early postnatal mice (XLKO). FGF23 elevation in response to parathyroid hormone, a stimulator of FGF23 production via cAMP, was intact in XLKO mice, while skeletal levels of protein kinase C isoforms \u03b1 and \u03b4 (PKC\u03b1 and PKC\u03b4) were diminished. XL\u03b1s ablation in osteocyte-like Ocy454 cells suppressed the levels of FGF23 mRNA, inositol 1,4,5-trisphosphate (IP3), and PKC\u03b1\/PKC\u03b4 proteins. PKC activation in vivo via injecting phorbol myristate acetate (PMA) or by constitutively active Gq\u03b1-Q209L in osteocytes and osteoblasts promoted FGF23 production. Molecular studies showed that the PKC activation\u2013induced FGF23 elevation was dependent on MAPK signaling. The baseline PKC activity was elevated in bones of Hyp mice, a model of XLH. XL\u03b1s ablation significantly, but modestly, reduced serum FGF23 and elevated serum phosphate in Hyp mice. These findings reveal a potentially hitherto-unknown mechanism of FGF23 synthesis involving a G protein\u2013coupled IP3\/PKC pathway, which may be targeted to fine-tune FGF23 levels.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.125007","type":"journal-article","created":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T11:01:02Z","timestamp":1567594862000},"source":"Crossref","is-referenced-by-count":28,"title":["A G protein\u2013coupled, IP3\/protein kinase C pathway controlling the synthesis of phosphaturic hormone FGF23"],"prefix":"10.1172","volume":"4","author":[{"given":"Qing","family":"He","sequence":"first","affiliation":[{"name":"Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren T.","family":"Shumate","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9996-6889","authenticated-orcid":true,"given":"Julia","family":"Matthias","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cumhur","family":"Aydin","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Endodontics, Gulhane Faculty of Dentistry, University of Health Sciences, Ankara, Turkey."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc N.","family":"Wein","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan M.","family":"Spatz","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Goetz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Pharmacology, New York University School of Medicine, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2434-9437","authenticated-orcid":true,"given":"Moosa","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Pharmacology, New York University School of Medicine, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6592-1343","authenticated-orcid":true,"given":"Antonius","family":"Plagge","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Divieti Pajevic","sequence":"additional","affiliation":[{"name":"Department of Molecular & Cell Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Bastepe","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2019,9,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.051308.111339"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2010.17"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.218"},{"key":"B4","unstructured":"Carpenter TO. 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