ArticleThe Journal of biological chemistry2008
Calcineurin B homologous protein 3 promotes the biosynthetic maturation, cell surface stability, and optimal transport of the Na+/H+ exchanger NHE1 isoform.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 55 citations in OpenAlex.
- NHE1 in Gastrointestinal Inflammation and Cancer: A Double-Edged Regulator.Digestive diseases and sciences · 2026Review
- A conserved ER protein prevents lipotoxicity by stimulating the key enzyme in glycerolipid synthesis.Nature communications · 2026Article
- Proteomics and Incident Kidney Failure in Individuals With CKD: The African American Study of Kidney Disease and Hypertension and the Boston Kidney Biopsy Cohort.Kidney medicine · 2024Article
- Structure and mechanism of the human NHE1-CHP1 complex.Nature communications · 2021Article
- Involvement of CHP2 in the Development of Non-Small Cell Lung Cancer and Patients' Poor Prognosis.Applied immunohistochemistry & molecular morphology : AIMM · 2020Article
- Calcineurin B homologous protein 3 binds with high affinity to the CHP binding domain of the human sodium/proton exchanger NHE1.Scientific reports · 2018Article
- Tescalcin/c-Src/IGF1Rβ-mediated STAT3 activation enhances cancer stemness and radioresistant properties through ALDH1.Scientific reports · 2018Article
- Phosphorylation of NHE3-SMolecular biology of the cell · 2017Article
- Emerging roles of the single EF-hand Ca2+ sensor tescalcin in the regulation of gene expression, cell growth and differentiation.Journal of cell science · 2016Review
- Tescalcin expression contributes to invasive and metastatic activity in colorectal cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Aldosterone Upregulates Transient Receptor Potential Melastatin 7 (TRPM7).The Journal of biological chemistry · 2016Article
- Article
- Regulation of Cop9 signalosome activity by the EF-hand Ca2+-binding protein tescalcin.Journal of cell science · 2014Article
- The EF-hand calcium-binding protein tescalcin is a potential oncotarget in colorectal cancer.Oncotarget · 2014Article
- The biophysical and molecular basis of intracellular pH sensing by Na+/H+ exchanger-3.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- CHP1-mediated NHE1 biosynthetic maturation is required for Purkinje cell axon homeostasis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Article
- Role of NHE1 in Nociception.Pain research and treatment · 2013Article
- N-myristoylation and Ca2+ binding of calcineurin B homologous protein CHP3 are required to enhance Na+/H+ exchanger NHE1 half-life and activity at the plasma membrane.The Journal of biological chemistry · 2012Article
- Calcineurin homologous protein: a multifunctional Ca2+-binding protein family.American journal of physiology. Renal physiology · 2012Review
Corrections and comments
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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
Calcineurin B homologous protein (CHP) 1 and 2 are Ca(2+)-binding proteins that modulate several cellular processes, including cytoplasmic pH by positively regulating plasma membrane-type Na(+)/H(+) exchangers (NHEs). Recently another CHP-related protein, termed tescalcin or CHP3, was also shown to interact with the ubiquitous NHE1 isoform, but seemingly suppressed its activity. However, the precise physical and functional nature of this association was not examined in detail. In this study, biochemical and cellular studies were undertaken to further delineate this relationship. Glutathione S-transferase-NHE1 fusion protein pulldown assays revealed that full-length CHP3 binds directly to the proximal juxtamembrane C-terminal region (amino acids 505-571) of rat NHE1 in the same region that binds CHP1 and CHP2. The interaction was further validated by coimmunoprecipitation and coimmunolocalization experiments using full-length CHP3 and wild-type NHE1 in transfected Chinese hamster ovary AP-1 cells. Simultaneous mutation of four hydrophobic residues within this region ((530)FLDHLL(535)) to either Ala, Gln, or Arg (FL-A, FL-Q, or FL-R) abrogated this interaction both in vitro and in intact cells. The NHE1 mutants were sorted properly to the cell surface but showed markedly reduced (FL-A) or minimal (FL-R and FL-Q) activity. Interestingly, and contrary to an earlier finding, ectopic coexpression of CHP3 up-regulated the cell surface activity of wild-type NHE1. This stimulation was not observed with the CHP3 binding-defective mutants. Mechanistically, overexpression of CHP3 did not alter the H(+) sensitivity of wild-type NHE1 but rather promoted its biosynthetic maturation and half-life at the cell surface, thereby increasing the steady-state abundance of functional NHE1 protein.
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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.