ArticleMolecular and cellular biology2012
Na(+)/H(+) exchanger 1 directly binds to calcineurin A and activates downstream NFAT signaling, leading to cardiomyocyte hypertrophy.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 56 citations in OpenAlex.
- The clinical missense variant E282K in PPP3CA/calcineurin shifts substrate dephosphorylation by altering active site recruitment.Nature communications · 2026Article
- Adaptation of Natural Killer Cells to Hypoxia: A Review of the Transcriptional, Translational, and Metabolic Processes.ImmunoTargets and therapy · 2025Review
- Lactate and Lactylation: Dual Regulators of T-Cell-Mediated Tumor Immunity and Immunotherapy.Biomolecules · 2024Review
- Human disease-associated calmodulin mutations alter calcineurin function through multiple mechanisms.Cell calcium · 2023Article
- A cellular atlas of calcineurin signaling.Biochimica et biophysica acta. Molecular cell research · 2023Review
- Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence?Heart failure reviews · 2022Review
- The Remaining Conundrum of the Role of the NaReviews in cardiovascular medicine · 2022Review
- NaPharmaceuticals (Basel, Switzerland) · 2022Review
- LDHA: The Obstacle to T cell responses against tumor.Frontiers in oncology · 2022Review
- Calcineurin in the heart: New horizons for an old friend.Cellular signalling · 2021Review
- A Review of Calcineurin Biophysics with Implications for Cardiac Physiology.International journal of molecular sciences · 2021Review
- Dynamic NaeLife · 2021Article
- Overexpression of NaThe Journal of biological chemistry · 2019Article
- Molecular basis for the binding and selective dephosphorylation of NaNature communications · 2019Article
- Lactate dehydrogenase A: A key player in carcinogenesis and potential target in cancer therapy.Cancer medicine · 2018Review
- Identification of novel macropinocytosis inhibitors using a rational screen of Food and Drug Administration-approved drugs.British journal of pharmacology · 2018Article
- Functions of intrinsic disorder in transmembrane proteins.Cellular and molecular life sciences : CMLS · 2017Review
- Calcineurin signaling in the heart: The importance of time and place.Journal of molecular and cellular cardiology · 2017Review
- Mrp Antiporters Have Important Roles in Diverse Bacteria and Archaea.Frontiers in microbiology · 2017Review
- Sumoylation-independent activation of Calcineurin-NFAT-signaling via SUMO2 mediates cardiomyocyte hypertrophy.Scientific reports · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The calcineurin A (CaNA) subunit was identified as a novel binding partner of plasma membrane Na(+)/H(+) exchanger 1 (NHE1). CaN is a Ca(2+)-dependent phosphatase involved in many cellular functions, including cardiac hypertrophy. Direct binding of CaN to the (715)PVITID(720) sequence of NHE1, which resembles the consensus CaN-binding motif (PXIXIT), was observed. Overexpression of NHE1 promoted serum-induced CaN/nuclear factor of activated T cells (NFAT) signaling in fibroblasts, as indicated by enhancement of NFAT promoter activity and nuclear translocation, which was attenuated by NHE1 inhibitor. In neonatal rat cardiomyocytes, NHE1 stimulated hypertrophic gene expression and the NFAT pathway, which were inhibited by a CaN inhibitor, FK506. Importantly, CaN activity was strongly enhanced with increasing pH, so NHE1 may promote CaN/NFAT signaling via increased intracellular pH. Indeed, Na(+)/H(+) exchange activity was required for NHE1-dependent NFAT signaling. Moreover, interaction of CaN with NHE1 and clustering of NHE1 to lipid rafts were also required for this response. Based on these results, we propose that NHE1 activity may generate a localized membrane microdomain with higher pH, thereby sensitizing CaN to activation and promoting NFAT signaling. In cardiomyocytes, such signaling can be a pathway of NHE1-dependent hypertrophy.
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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.