Fibroblast growth factor-23-mediated inhibition of renal phosphate transport in mice requires sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) and synergizes with parathyroid hormone.
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Fibroblast growth factor-23 (FGF-23) inhibits sodium-dependent phosphate transport in brush border membrane vesicles derived from hormone-treated kidney slices of the mouse and in mouse proximal tubule cells by processes involving mitogen-activated protein kinase (MAPK) but not protein kinase A (PKA) or protein kinase C (PKC). By contrast, phosphate transport in brush border membrane vesicles and proximal tubule cells from sodium-hydrogen exchanger regulatory factor-1 (NHERF-1)-null mice were resistant to the inhibitory effect of FGF-23 (10(-9) m). Infection of NHERF-1-null proximal tubule cells with wild-type adenovirus-GFP-NHERF-1 increased basal phosphate transport and restored the inhibitory effect of FGF-23. Infection with adenovirus-GFP-NHERF-1 containing a S77A or T95D mutation also increased basal phosphate transport, but the cells remained resistant to FGF-23 (10(-9) m). Low concentrations of FGF-23 (10(-13) m) and PTH (10(-11) m) individually did not inhibit phosphate transport or activate PKA, PKC, or MAPK. When combined, however, these hormones markedly inhibited phosphate transport associated with activation of PKC and PKA but not MAPK. These studies indicate that FGF-23 inhibits phosphate transport in the mouse kidney by processes that involve the scaffold protein NHERF-1. In addition, FGF-23 synergizes with PTH to inhibit phosphate transport by facilitating the activation of the PTH signal transduction pathway.
SubjectKidney Tubules, Proximal
Cyclic AMP-Dependent Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Protein Kinase C
Fibroblast Growth Factors
Amino Acid Substitution
Published Version (Please cite this version)10.1074/jbc.m111.288357
Publication InfoBiswas, Rajatsubhra; Shenolikar, Shirish; Steplock, Deborah; & Weinman, Edward J (2011). Fibroblast growth factor-23-mediated inhibition of renal phosphate transport in mice requires sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) and synergizes with parathyroid hormone. The Journal of biological chemistry, 286(43). pp. 37216-37221. 10.1074/jbc.m111.288357. Retrieved from https://hdl.handle.net/10161/17240.
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Professor Emeritus of Psychiatry and Behavioral Sciences
Protein phosphorylation controls a wide range of physiological processes in mammalian tissues. Phosphorylation state of cellular proteins is controlled by the opposing actions of protein kinases and phosphatases that are regulated by hormones, neurotransmitters, growth factors and other environmental cues. Our research attempts to understand the communication between protein kinases and phosphatases that dictates cellular protein phosphorylation and the cell's response to hormones. Over the