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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.

dc.contributor.author Biswas, Rajatsubhra
dc.contributor.author Shenolikar, Shirish
dc.contributor.author Steplock, Deborah
dc.contributor.author Weinman, Edward J
dc.date.accessioned 2018-07-16T17:11:23Z
dc.date.available 2018-07-16T17:11:23Z
dc.date.issued 2011-10
dc.identifier.issn 0021-9258
dc.identifier.issn 1083-351X
dc.identifier.uri https://hdl.handle.net/10161/17240
dc.description.abstract 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.
dc.language eng
dc.publisher AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.relation.ispartof The Journal of biological chemistry
dc.relation.isversionof 10.1074/jbc.m111.288357
dc.subject Kidney Tubules, Proximal
dc.subject Animals
dc.subject Mice, Knockout
dc.subject Mice
dc.subject Adenoviridae
dc.subject Phosphates
dc.subject Parathyroid Hormone
dc.subject Cyclic AMP-Dependent Protein Kinases
dc.subject Extracellular Signal-Regulated MAP Kinases
dc.subject Protein Kinase C
dc.subject Fibroblast Growth Factors
dc.subject Sodium-Hydrogen Antiporter
dc.subject Phosphoproteins
dc.subject Transduction, Genetic
dc.subject Amino Acid Substitution
dc.subject Ion Transport
dc.subject Mutation, Missense
dc.title 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.
dc.type Journal article
dc.date.updated 2018-07-16T17:11:22Z
pubs.begin-page 37216
pubs.end-page 37221
pubs.issue 43
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Psychiatry & Behavioral Sciences, Translational Neuroscience
pubs.organisational-group Psychiatry & Behavioral Sciences
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 286
duke.contributor.orcid Shenolikar, Shirish|0000-0003-0540-6328


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