Regulation of calcium and phosphate metabolism by inorganic phosphate sensor (type IIc Na/Pi cotransporter)

磷酸盐离子对正常骨矿化至关重要，磷酸盐在许多其他生物过程中起着至关重要的作用，如信号转导、核苷酸代谢和酶调节。在本研究中，我们克隆了一个假定的无机磷酸盐传感器（IIc Na/Pi共转运体），它在肾脏、骨骼和大脑中表达。一种新的磷酸化因子，成纤维细胞生长因子23，降低了肾脏中无机磷酸盐传感器（IIc型）的表达。我们证明了klotho和FGF23通过一个共同的信号通路起作用。与单独结合FGFR或klotho相比，FGF23与klotho/FGF受体（FGFR）复合物结合的亲和力更高。此外，klotho显著增强了FGF23诱导各种类型细胞中FGF受体底物和ERK磷酸化的能力，这表明klotho是FGF23激活FGF信号通路所必需的辅助因子。最后，我们证明了FGF23/klotho信号是调节肾脏和骨骼中无机磷酸盐传感器（IIc型）表达所必需的。

Phosphate ions ate critical for normal bone mineralization, and phosphate plays a vital role in a number of other biological processes such as signal transduction, nucleotide metabolism, and enzyme regulation. In the present study, we have cloned a putative inorganic phosphate sensor (type IIc Na/Pi cotransporter) that is expressed in kidney, bone and brain. A novel phosphaturic factor, fibroblast growth factor 23,decreased the expression of inorganic phosphate sensor (type IIc) in the kidney. We demonstrated that klotho and FGF23 functions via a common signaling pathway. FGF23 binds to the klotho/FGF receptor (FGFR) complex with higher affinity than it binds to FGFR or klotho alone. In addition, klotho significantly enhances the ability of FGF23 to induce phosphorylation of an FGF receptor substrate and ERK in various types of cells, suggesting that klotho functions as a cofactor essential for activation of FGF signaling by FGF23. Finally, we demonstrated that FGF23/klotho signaling is necessary to regulate the expression of inorganic phosphate sensor (type IIc) in the kidney and bone.