ArticleAmerican journal of physiology. Cell physiology2015
Regulation of NHE3 by lysophosphatidic acid is mediated by phosphorylation of NHE3 by RSK2.
Article in American journal of physiology. Cell physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 31 citations in OpenAlex.
- Regulation of the intestinal NaAmerican journal of physiology. Cell physiology · 2024Article
- Porcine epidemic diarrhea virus causes diarrhea by activating EGFR to regulates NHE3 activity and mobility on plasma membrane.Frontiers in microbiology · 2023Article
- p90RSK2, a new MLCK mediates contractility in myosin light chain kinase null smooth muscle.Frontiers in physiology · 2023Article
- Activated PyK2 and Its Associated Molecules Transduce Cellular Signaling from the Cancerous Milieu for Cancer Metastasis.International journal of molecular sciences · 2022Review
- Optimization of Ultrafast Proteomics Using an LC-Quadrupole-Orbitrap Mass Spectrometer with Data-Independent Acquisition.Journal of proteome research · 2022Article
- Survival of Stem Cells and Progenitors in the Intestine Is Regulated by LPACellular and molecular gastroenterology and hepatology · 2022Article
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- Crosstalk between Sodium-Glucose Cotransporter Inhibitors and Sodium-Hydrogen Exchanger 1 and 3 in Cardiometabolic Diseases.International journal of molecular sciences · 2021Review
- Targeting Lysophosphatidic Acid in Cancer: The Issues in Moving from Bench to Bedside.Cancers · 2019Review
- The cardenolide ouabain suppresses coronaviral replication via augmenting a NaToxicology and applied pharmacology · 2018Article
- Expression of lysophosphatidic acid receptor 5 is necessary for the regulation of intestinal NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018Article
- SLC9 Gene Family: Function, Expression, and Regulation.Comprehensive Physiology · 2018Review
- Lysophosphatidic Acid Receptor 1 Is Important for Intestinal Epithelial Barrier Function and Susceptibility to Colitis.The American journal of pathology · 2018Article
- Phosphorylation of NHE3-SMolecular biology of the cell · 2017Article
- Bacterial Expression, Purification and In Vitro Phosphorylation of Full-Length Ribosomal S6 Kinase 2 (RSK2).PloS one · 2016Article
- Restoration of Na+/H+ exchanger NHE3-containing macrocomplexes ameliorates diabetes-associated fluid loss.The Journal of clinical investigation · 2015Article
- Regulators of Slc4 bicarbonate transporter activity.Frontiers in physiology · 2015Review
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4 authors at 1 institution in 1 country.
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Abstract
Na(+)/H(+) exchange by Na(+)/H(+) exchanger 3 (NHE3) is a major route of sodium absorption in the intestine and kidney. We have shown previously that lysophosphatidic acid (LPA), a small phospholipid produced ubiquitously by all types of cells, stimulates NHE3 via LPA5 receptor. Stimulation of NHE3 activity by LPA involves LPA5 transactivating EGF receptor (EGFR) in the apical membrane. EGFR activates proline-rich tyrosine kinase 2 (Pyk2) and ERK, both of which are necessary for NHE3 regulation. However, Pyk2 and ERK are regulated by EGFR via independent pathways and appear to converge on an unidentified intermediate that ultimately targets NHE3. The p90 ribosomal S6 kinase (RSK) family of Ser/Thr protein kinases is a known effector of EGFR and ERK. Hence, we hypothesized that RSK may be the convergent effector of Pyk2 and ERK although it is not known whether Pyk2 regulates RSK. In this study, we show that Pyk2 is necessary for the maintenance of phosphoinositide-dependent kinase 1 (PDK1) autophosphorylation, and knockdown of Pyk2 or PDK1 mitigated LPA-induced phosphorylation of RSK and stimulation of NHE3 activity. Additionally, we show that RSK2, but not RSK1, is responsible for NHE3 regulation. RSK2 interacts with NHE3 at the apical membrane domain, where it phosphorylates NHE3. Alteration of S663 of NHE3 ablated LPA-induced phosphorylation of NHE3 and stimulation of the transport activity. Our study identifies RSK2 as a new kinase that regulates NHE3 activity by direct phosphorylation.
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