ArticleThe Journal of clinical investigation2004
Pyk2 activation is integral to acid stimulation of sodium/hydrogen exchanger 3.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 85 citations in OpenAlex.
- Disrupting oncogenic signaling in triple negative breast cancer: The interplay of Cx43, Pyk2, and Src in MDA-MB-231 cells.Cell and tissue research · 2026Article
- Inhibition of Pyk2 prevents Cx43 remodeling and cardiomyocyte injury during hypoxic and adrenergic stress.Journal of molecular and cellular cardiology · 2026Article
- Acid-sensing ion channels and downstream signalling in cancer cells: is there a mechanistic link?Pflugers Archiv : European journal of physiology · 2024Review
- Effects of extracellular metabolic acidosis and out-of-equilibrium COFrontiers in physiology · 2024Article
- How protons pave the way to aggressive cancers.Nature reviews. Cancer · 2023Review
- Inhibition of Pyk2 Improves Cx43 Intercalated Disc Localization, Infarct Size, and Cardiac Function in Rats With Heart Failure.Circulation. Heart failure · 2023Article
- Activated PyK2 and Its Associated Molecules Transduce Cellular Signaling from the Cancerous Milieu for Cancer Metastasis.International journal of molecular sciences · 2022Review
- Acidic environments trigger intracellular H+-sensing FAK proteins to re-balance sarcolemmal acid-base transporters and auto-regulate cardiomyocyte pH.Cardiovascular research · 2022Article
- Kidney metabolism and acid-base control: back to the basics.Pflugers Archiv : European journal of physiology · 2022Review
- Physiological relevance of proton-activated GPCRs.Pflugers Archiv : European journal of physiology · 2022Review
- The recycling regulation of sodium-hydrogen exchanger isoform 3(NHE3) in epithelial cells.Cell cycle (Georgetown, Tex.) · 2021Review
- The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases.Frontiers in synaptic neuroscience · 2021Review
- Mechanisms of Metabolic Acidosis-Induced Kidney Injury in Chronic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2020Article
- Article
- Pyk2-dependent phosphorylation of LSR enhances localization of LSR and tricellulin at tricellular tight junctions.PloS one · 2019Article
- Acid-base regulation in the renal proximal tubules: using novel pH sensors to maintain homeostasis.American journal of physiology. Renal physiology · 2018Review
- Acid Stimulation of the Citrate Transporter NaDC-1 Requires Pyk2 and ERK1/2 Signaling Pathways.Journal of the American Society of Nephrology : JASN · 2018Article
- Role of Receptor Protein Tyrosine Phosphatase γ in Sensing Extracellular CO2 and HCO3.Journal of the American Society of Nephrology : JASN · 2016Article
- pH sensors and ion Transporters: Potential therapeutic targets for acid-base disorders.International journal of pharma research & review · 2016Article
- Molecular mechanisms and regulation of urinary acidification.Comprehensive Physiology · 2014Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The present study examines the role of Pyk2 in acid regulation of sodium/hydrogen exchanger 3 (NHE3) activity in OKP cells, a kidney proximal tubule epithelial cell line. Incubation of OKP cells in acid media caused a transient increase in Pyk2 phosphorylation that peaked at 30 seconds and increased Pyk2/c-Src binding at 90 seconds. Pyk2 isolated by immunoprecipitation and studied in a cell-free system was activated and phosphorylated at acidic pH. Acid activation of Pyk2 (a) was specific for Pyk2 in that acid did not activate focal adhesion kinase, (b) required calcium, and (c) was associated with increased affinity for ATP. Transfection of OKP cells with dominant-negative pyk2(K457A) or small interfering pyk2 duplex RNA blocked acid activation of NHE3, while neither had an effect on glucocorticoid activation of NHE3. In addition, pyk2(K457A) blocked acid activation of c-Src kinase, which is also required for acid regulation of NHE3. The present results demonstrate that Pyk2 is directly activated by acidic pH and that Pyk2 activation is required for acid activation of c-Src kinase and NHE3. Given that partially purified Pyk2 can be activated by acid in a cell-free system, Pyk2 may serve as the pH sensor that initiates the acid-regulated signaling cascade involved in NHE3 regulation.
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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.