ArticleThe Journal of biological chemistry2010
Cooperativity between the phosphorylation of Thr95 and Ser77 of NHERF-1 in the hormonal regulation of renal phosphate transport.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- 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
- Tmem174, a regulator of phosphate transporter prevents hyperphosphatemia.Scientific reports · 2022Article
- Noncanonical Sequences Involving NHERF1 Interaction with NPT2A Govern Hormone-Regulated Phosphate Transport: Binding Outside the Box.International journal of molecular sciences · 2021Review
- Role of the putative PKC phosphorylation sites of the type IIc sodium-dependent phosphate transporter in parathyroid hormone regulation.Clinical and experimental nephrology · 2019Article
- Parallel Post-Translational Modification Scanning Enhancing Hydrogen-Deuterium Exchange-Mass Spectrometry Coverage of Key Structural Regions.Analytical chemistry · 2019Article
- Parathyroid hormone initiates dynamic NHERF1 phosphorylation cycling and conformational changes that regulate NPT2A-dependent phosphate transport.The Journal of biological chemistry · 2019Article
- NaPi-IIa interacting partners and their (un)known functional roles.Pflugers Archiv : European journal of physiology · 2019Review
- Physiological regulation of phosphate by vitamin D, parathyroid hormone (PTH) and phosphate (Pi).Pflugers Archiv : European journal of physiology · 2019Review
- Dynamic relocalization of NHERF1 mediates chemotactic migration of ovarian cancer cells toward lysophosphatidic acid stimulation.Experimental & molecular medicine · 2017Article
- Role of the PDZ-scaffold protein NHERF1/EBP50 in cancer biology: from signaling regulation to clinical relevance.Oncogene · 2017Review
- RNA sequencing and proteomics approaches reveal novel deficits in the cortex ofMolecular autism · 2017Article
- Convergent Signaling Pathways Regulate Parathyroid Hormone and Fibroblast Growth Factor-23 Action on NPT2A-mediated Phosphate Transport.The Journal of biological chemistry · 2016Article
- The NHERF1 PDZ1 domain and IRBIT interact and mediate the activation of Na+/H+ exchanger 3 by ANG II.American journal of physiology. Renal physiology · 2016Article
- Regulation of renal phosphate handling: inter-organ communication in health and disease.Journal of bone and mineral metabolism · 2016Review
- Restoration of Na+/H+ exchanger NHE3-containing macrocomplexes ameliorates diabetes-associated fluid loss.The Journal of clinical investigation · 2015Article
- Characterization of FGF23-Dependent Egr-1 Cistrome in the Mouse Renal Proximal Tubule.PloS one · 2015Article
- The SLC34 family of sodium-dependent phosphate transporters.Pflugers Archiv : European journal of physiology · 2014Review
- Minimal models for cell-cycle control based on competitive inhibition and multisite phosphorylations of Cdk substrates.Biophysical journal · 2013Article
- EBP50 promotes focal adhesion turnover and vascular smooth muscle cells migration.Journal of molecular and cellular cardiology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The phosphorylation of the sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) plays a key role in the regulation of renal phosphate transport by parathyroid hormone (PTH) and dopamine. Ser(77) in the first PDZ domain of NHERF-1 is a downstream target of both hormones. The current experiments explore the role of Thr(95), another phosphate acceptor site in the PDZ I domain, on hormone-mediated regulation of phosphate transport in the proximal tubule of the kidney. The substitution of alanine for threonine at position 95 (T95A) significantly decreased the rate and extent of in vitro phosphorylation of Ser(77) by PKC. In NHERF-1-null proximal tubule cells, neither PTH nor dopamine inhibited sodium-dependent phosphate transport. Infection of the cells with adenovirus expressing full-length WT GFP-NHERF-1 increased basal phosphate transport and restored the inhibitory effect of both PTH and dopamine. Infection with full-length NHERF-1 containing a T95A mutation, however, increased basal phosphate transport but not the responsiveness to either hormone. As determined by surface plasmon resonance, the substitution of serine for aspartic acid (S77D) in the PDZ I domain decreased the binding affinity to the sodium-dependent phosphate transporter 2a (Npt2a) as compared with WT PDZ I, but a T95D mutation had no effect on binding. Finally, cellular studies indicated that both PTH and dopamine treatment increased the phosphorylation of Thr(95). These studies indicate a remarkable cooperativity between the phosphorylation of Thr(95) and Ser(77) of NHERF-1 in the hormonal regulation of renal phosphate transport. The phosphorylation of Thr(95) facilitates the phosphorylation of Ser(77). This, in turn, results in the dissociation of NHERF-1 from Npt2a and a decrease in phosphate transport in renal proximal tubule cells.
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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.