Fig. 1.

Summary of the biochemical pathways for parathyroid hormone (PTH)-, dopamine-, and FGF-23-mediated inhibition of phosphate transport in the renal proximal convoluted tubule. PTH interacts with the PTH1 receptor in renal proximal cells to activate PKC and PKA, resulting in the phosphorylation of sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) and the dissociation of the proximal tubule sodium-dependent phosphate transporter (Npt2a) from NHERF-1. The unbound Npt2a transporter then interacts with other proteins that facilitate its endocytosis from the apical membrane, resulting in decreased phosphate transport. Dopamine interacts with renal D1-like receptors to activate the cAMP/PKA pathway, which, in turn, activates PKC. Like PTH, activated PKC phosphorylates NHERF-1 and dissociates Npt2a/NHERF-1 complexes, resulting in decreased phosphate transport. FGF-23 activates MAPK and phosphorylates NHERF-1. The site-specific phosphorylation of NHERF-1 by FGF-23, however, differs from that of PTH and dopamine (Fig. 2).