ArticleMolecular biology of the cell2008
Casein kinase 2 binds to the C terminus of Na+/H+ exchanger 3 (NHE3) and stimulates NHE3 basal activity by phosphorylating a separate site in NHE3.
Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- Regulation of the intestinal NaAmerican journal of physiology. Cell physiology · 2024Article
- A Novel Peptide Prevents Enterotoxin- and Inflammation-Induced Intestinal Fluid Secretion by Stimulating Sodium-Hydrogen Exchanger 3 Activity.Gastroenterology · 2023Article
- mOrange2, a Genetically Encoded, pH Sensitive Fluorescent Protein, is an Alternative to BCECF-AM to Measure Intracellular pH to Determine NHE3 and DRA Activity.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2022Article
- The NaFrontiers in physiology · 2022Review
- Identification of Intestinal NaCl Absorptive-Anion Secretory Cells: Potential Functional Significance.Frontiers in physiology · 2022Review
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- The recycling regulation of sodium-hydrogen exchanger isoform 3(NHE3) in epithelial cells.Cell cycle (Georgetown, Tex.) · 2021Review
- Altered absorptive function in the gall bladder during cholesterol gallstone formation is associated with abnormal NHE3 complex formation.Journal of physiology and biochemistry · 2020Article
- NHERF3 is necessary forAmerican journal of physiology. Cell physiology · 2019Article
- G protein-coupled receptor 37L1 regulates renal sodium transport and blood pressure.American journal of physiology. Renal physiology · 2019Article
- SLC9 Gene Family: Function, Expression, and Regulation.Comprehensive Physiology · 2018Review
- Trafficking Ion Transporters to the Apical Membrane of Polarized Intestinal Enterocytes.Cold Spring Harbor perspectives in biology · 2018Review
- Both NHERF3 and NHERF2 are necessary for multiple aspects of acute regulation of NHE3 by elevated CaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Phosphorylation of NHE3-SMolecular biology of the cell · 2017Article
- The Pathogenic Role of NLRP3 Inflammasome Activation in Inflammatory Bowel Diseases of Both Mice and Humans.Journal of Crohn's & colitis · 2017Article
- PDZ domain-dependent regulation of NHE3 protein by both internal Class II and C-terminal Class I PDZ-binding motifs.The Journal of biological chemistry · 2017Article
- Regulation of NHE3 by lysophosphatidic acid is mediated by phosphorylation of NHE3 by RSK2.American journal of physiology. Cell physiology · 2015Article
- Nonsynonymous single nucleotide polymorphisms of NHE3 differentially decrease NHE3 transporter activity.American journal of physiology. Cell physiology · 2015Article
- Cyclic GMP kinase II (cGKII) inhibits NHE3 by altering its trafficking and phosphorylating NHE3 at three required sites: identification of a multifunctional phosphorylation site.The Journal of biological chemistry · 2015Article
- Molecular mechanisms and regulation of urinary acidification.Comprehensive Physiology · 2014Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Na(+)/H(+) exchanger 3 (NHE3) is the epithelial-brush border isoform responsible for most intestinal and renal Na(+) absorption. Its activity is both up- and down-regulated under normal physiological conditions, and it is inhibited in most diarrheal diseases. NHE3 is phosphorylated under basal conditions and Ser/Thr phosphatase inhibitors stimulate basal exchange activity; however, the kinases involved are unknown. To identify kinases that regulate NHE3 under basal conditions, NHE3 was immunoprecipitated; LC-MS/MS of trypsinized NHE3 identified a novel phosphorylation site at S(719) of the C terminus, which was predicted to be a casein kinase 2 (CK2) phosphorylation site. This was confirmed by an in vitro kinase assay. The NHE3-S719A mutant but not NHE3-S719D had reduced NHE3 activity due to less plasma membrane NHE3. This was due to reduced exocytosis plus decreased plasma membrane delivery of newly synthesized NHE3. Also, NHE3 activity was inhibited by the CK2 inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole DMAT when wild-type NHE3 was expressed in fibroblasts and Caco-2 cells, but the NHE3-S(719) mutant was fully resistant to DMAT. CK2 bound to the NHE3 C-terminal domain, between amino acids 590 and 667, a site different from the site it phosphorylates. CK2 binds to the NHE3 C terminus and stimulates basal NHE3 activity by phosphorylating a separate single site on the NHE3 C terminus (S(719)), which affects NHE3 trafficking.
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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.