| First Author | Andrukhova O | Year | 2012 |
| Journal | Bone | Volume | 51 |
| Issue | 3 | Pages | 621-8 |
| PubMed ID | 22647968 | Mgi Jnum | J:192420 |
| Mgi Id | MGI:5465064 | Doi | 10.1016/j.bone.2012.05.015 |
| Citation | Andrukhova O, et al. (2012) FGF23 acts directly on renal proximal tubules to induce phosphaturia through activation of the ERK1/2-SGK1 signaling pathway. Bone 51(3):621-8 |
| abstractText | Fibroblast growth factor-23 (FGF23) is a bone-derived endocrine regulator of phosphate homeostasis which inhibits renal tubular phosphate reabsorption. Binding of circulating FGF23 to FGF receptors in the cell membrane requires the concurrent presence of the co-receptor alphaKlotho. It is still controversial whether alphaKlotho is expressed in the kidney proximal tubule, the principal site of phosphate reabsorption. Hence, it has remained an enigma as to how FGF23 downregulates renal phosphate reabsorption. Here, we show that renal proximal tubular cells do express the co-receptor alphaKlotho together with cognate FGF receptors, and that FGF23 directly downregulates membrane expression of the sodium-phosphate cotransporter NaPi-2a by serine phosphorylation of the scaffolding protein Na(+)/H(+) exchange regulatory cofactor (NHERF)-1 through ERK1/2 and serum/glucocorticoid-regulated kinase-1 signaling. |
