ArticleThe Journal of biological chemistry2010
Na/H exchanger regulatory factors control parathyroid hormone receptor signaling by facilitating differential activation of G(alpha) protein subunits.
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 33 papers.
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Who cites it
33 citing papers in PubMed, 68 citations in OpenAlex.
- Review
- Long Term High-Salt Diet Induces Cognitive Impairments via Down-Regulating SHANK1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Caveolin-1 Regulates Parathyroid Hormone (PTH)-Related Protein (PTHrP) Actions on PTH Receptor Type 1 in Bone Cells.Journal of cellular physiology · 2025Article
- The molecular sociology of NHERF1 PDZ proteins controlling renal hormone-regulated phosphate transport.Bioscience reports · 2024Article
- Scribble scrambles parathyroid hormone receptor interactions to regulate phosphate and vitamin D homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- RGS14 regulates PTH- and FGF23-sensitive NPT2A-mediated renal phosphate uptake via binding to the NHERF1 scaffolding protein.The Journal of biological chemistry · 2022Article
- GPCRs in the regulation of the functional activity of multipotent mesenchymal stromal cells.Frontiers in cell and developmental biology · 2022Review
- Physical Activity-Dependent Regulation of Parathyroid Hormone and Calcium-Phosphorous Metabolism.International journal of molecular sciences · 2020Review
- Loss of the NaThe American journal of pathology · 2019Article
- Parathyroid hormone initiates dynamic NHERF1 phosphorylation cycling and conformational changes that regulate NPT2A-dependent phosphate transport.The Journal of biological chemistry · 2019Article
- Heterotrimeric G proteins in the control of parathyroid hormone actions.Journal of molecular endocrinology · 2017Review
- Dynamic NHERF interaction with TRPC4/5 proteins is required for channel gating by diacylglycerol.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- A sequence upstream of canonical PDZ-binding motif within CFTR COOH-terminus enhances NHERF1 interaction.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- PTH1R Mutants Found in Patients with Primary Failure of Tooth Eruption Disrupt G-Protein Signaling.PloS one · 2016Article
- The PDZ Protein Na+/H+ Exchanger Regulatory Factor-1 (NHERF1) Regulates Planar Cell Polarity and Motile Cilia Organization.PloS one · 2016Article
- PTH receptor-1 signalling-mechanistic insights and therapeutic prospects.Nature reviews. Endocrinology · 2015Review
- Disruption of β-catenin binding to parathyroid hormone (PTH) receptor inhibits PTH-stimulated ERK1/2 activation.Biochemical and biophysical research communications · 2015Article
- Drug Transporters and Na+/H+ Exchange Regulatory Factor PSD-95/Drosophila Discs Large/ZO-1 Proteins.Pharmacological reviews · 2015Review
- Minireview: Role of intracellular scaffolding proteins in the regulation of endocrine G protein-coupled receptor signaling.Molecular endocrinology (Baltimore, Md.) · 2015Review
- Sustained signalling by PTH modulates IP3 accumulation and IP3 receptors through cyclic AMP junctions.Journal of cell science · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The Na/H exchanger regulatory factors, NHERF1 and NHERF2, are adapter proteins involved in targeting and assembly of protein complexes. The parathyroid hormone receptor (PTHR) interacts with both NHERF1 and NHERF2. The NHERF proteins toggle PTHR signaling from predominantly activation of adenylyl cyclase in the absence of NHERF to principally stimulation of phospholipase C when the NHERF proteins are expressed. We hypothesized that this signaling switch occurs at the level of the G protein. We measured G protein activation by [(35)S]GTPgammaS binding and G(alpha) subtype-specific immunoprecipitation using three different cellular models of PTHR signaling. These studies revealed that PTHR interactions with NHERF1 enhance receptor-mediated stimulation of G(alpha)(q) but have no effect on stimulation of G(alpha)(i) or G(alpha)(s). In contrast, PTHR associations with NHERF2 enhance receptor-mediated stimulation of both G(alpha)(q) and G(alpha)(i) but decrease stimulation of G(alpha)(s). Consistent with these functional data, NHERF2 formed cellular complexes with both G(alpha)(q) and G(alpha)(i), whereas NHERF1 was found to interact only with G(alpha)(q). These findings demonstrate that NHERF interactions regulate PTHR signaling at the level of G proteins and that NHERF1 and NHERF2 exhibit isotype-specific effects on G protein activation.
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