ArticleThe Journal of biological chemistry2016
Convergent Signaling Pathways Regulate Parathyroid Hormone and Fibroblast Growth Factor-23 Action on NPT2A-mediated Phosphate Transport.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Review
- Hypophosphatemic rickets: diagnosis and treatment.Archives of endocrinology and metabolism · 2026Review
- Elevated FGF23 Despite Biochemical Control Reveals Hidden Mineral Dysregulation in Chronic Hypoparathyroidism.Journal of the Endocrine Society · 2026Article
- Hypoparathyroidism: a brief historical overview for clinicians.Frontiers in endocrinology · 2026Review
- Prolonged Effects of COVID-19-Related Behavioral Restrictions on Neonatal Bone Metabolism: A Retrospective Study.Cureus · 2025Article
- Noncanonical RGS14 structural determinants control hormone-sensitive NPT2A-mediated phosphate transport.The Biochemical journal · 2025Article
- Distinct and overlapping RGS14 and RGS12 actions regulate NPT2A-mediated phosphate transport.Biochemical and biophysical research communications · 2024Article
- The Intricacies of Renal Phosphate Reabsorption-An Overview.International journal of molecular sciences · 2024Review
- The molecular sociology of NHERF1 PDZ proteins controlling renal hormone-regulated phosphate transport.Bioscience reports · 2024Article
- Exploring endocrine FGFs - structures, functions and biomedical applications.International journal of biochemistry and molecular biology · 2024Review
- [Current indications and operative strategy for renal hyperparathyroidism].Chirurgie (Heidelberg, Germany) · 2023Review
- Genetic Variants Associated With Mineral Metabolism Traits in Chronic Kidney Disease.The Journal of clinical endocrinology and metabolism · 2022Article
- RGS14 regulates PTH- and FGF23-sensitive NPT2A-mediated renal phosphate uptake via binding to the NHERF1 scaffolding protein.The Journal of biological chemistry · 2022Article
- The Complexities of Organ Crosstalk in Phosphate Homeostasis: Time to Put Phosphate Sensing Back in the Limelight.International journal of molecular sciences · 2021Review
- Association of vitamin D and FGF23 with serum ferritin in hypoparathyroid thalassemia: a case control study.BMC nephrology · 2020Article
- New roles of the NaAmerican journal of physiology. Renal physiology · 2020Review
- 1,25-Dihydroxyvitamin D Maintains Brush Border Membrane NaPi2a and Attenuates Phosphaturia in Hyp Mice.Endocrinology · 2019Article
- The Role of Fibroblast Growth Factor 23 in Inflammation and Anemia.International journal of molecular sciences · 2019Review
- Parathyroid hormone initiates dynamic NHERF1 phosphorylation cycling and conformational changes that regulate NPT2A-dependent phosphate transport.The Journal of biological chemistry · 2019Article
- Evidence for a role of PDZ domain-containing proteins to mediate hypophosphatemia in calcium stone formers.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2018Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Parathyroid hormone (PTH) and FGF23 are the primary hormones regulating acute phosphate homeostasis. Human renal proximal tubule cells (RPTECs) were used to characterize the mechanism and signaling pathways of PTH and FGF23 on phosphate transport and the role of the PDZ protein NHERF1 in mediating PTH and FGF23 effects. RPTECs express the NPT2A phosphate transporter, αKlotho, FGFR1, FGFR3, FGFR4, and the PTH receptor. FGFR1 isoforms are formed from alternate splicing of exon 3 and of exon 8 or 9 in Ir-like loop 3. Exon 3 was absent, but mRNA containing both exons 8 and 9 is present in cytoplasm. Using an FGFR1c-specific antibody together with mass spectrometry analysis, we show that RPTECs express FGFR-β1C. The data are consistent with regulated FGFR1 splicing involving a novel cytoplasmic mechanism. PTH and FGF23 inhibited phosphate transport in a concentration-dependent manner. At maximally effective concentrations, PTH and FGF23 equivalently decreased phosphate uptake and were not additive, suggesting a shared mechanism of action. Protein kinase A or C blockade prevented PTH but not FGF23 actions. Conversely, inhibiting SGK1, blocking FGFR dimerization, or knocking down Klotho expression disrupted FGF23 actions but did not interfere with PTH effects. C-terminal FGF23(180-251) competitively and selectively blocked FGF23 action without disrupting PTH effects. However, both PTH and FGF23-sensitive phosphate transport were abolished by NHERF1 shRNA knockdown. Extended treatment with PTH or FGF23 down-regulated NPT2A without affecting NHERF1. We conclude that FGFR1c and PTHR signaling pathways converge on NHERF1 to inhibit PTH- and FGF23-sensitive phosphate transport and down-regulate NPT2A.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.