ArticleMolecular and cellular biology2001
Trophic factor withdrawal: p38 mitogen-activated protein kinase activates NHE1, which induces intracellular alkalinization.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 159 citations in OpenAlex.
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- Regulation of the p38-MAPK pathway by hyperosmolarity and by WNK kinases.Scientific reports · 2022Article
- Regulation of proton partitioning in kinase-activating acute myeloid leukemia and its therapeutic implication.Leukemia · 2022Article
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- Amino Acids 785, 787 of the NaInternational journal of molecular sciences · 2021Article
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- Polarized Expression of Ion Channels and Solute Carrier Family Transporters on Heterogeneous Cultured Human Corneal Endothelial Cells.Investigative ophthalmology & visual science · 2020Article
- An overview of mammalian p38 mitogen-activated protein kinases, central regulators of cell stress and receptor signaling.F1000Research · 2020Review
- Structural and Functional Changes in the NaInternational journal of molecular sciences · 2019Review
- Angiotensin II-induced podocyte apoptosis is mediated by endoplasmic reticulum stress/PKC-δ/p38 MAPK pathway activation and trough increased NaBMC nephrology · 2018Article
- Interleukin-13 increases pendrin abundance to the cell surface in bronchial NCI-H292 cells via Rho/actin signaling.Pflugers Archiv : European journal of physiology · 2017Article
- Molecular machineries of pH dysregulation in tumor microenvironment: potential targets for cancer therapy.BioImpacts : BI · 2017Review
- The human Na(+)/H(+) exchanger 1 is a membrane scaffold protein for extracellular signal-regulated kinase 2.BMC biology · 2016Article
- Cancer: fundamentals behind pH targeting and the double-edged approach.OncoTargets and therapy · 2016Article
- Na(+)/H(+) exchange and hypoxic pulmonary hypertension.Pulmonary circulation · 2015Review
- Ion transporters in brain tumors.Current medicinal chemistry · 2015Review
- Structural and Functional Diversity of Estrogen Receptor Ligands.Current topics in medicinal chemistry · 2015Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Trophic factor withdrawal induces cell death by mechanisms that are incompletely understood. Previously we reported that withdrawal of interleukin-7 (IL-7) or IL-3 produced a rapid intracellular alkalinization, disrupting mitochondrial metabolism and activating the death protein Bax. We now observe that this novel alkalinization pathway is mediated by the pH regulator NHE1, as shown by the requirement for sodium, blocking by pharmacological inhibitors or use of an NHE1-deficient cell line, and the altered phosphorylation of NHE1. Alkalinization also required the stress-activated p38 mitogen-activated protein kinase (MAPK). Inhibition of p38 MAPK activity with pharmacological inhibitors or expression of a dominant negative kinase prevented alkalinization. Activated p38 MAPK directly phosphorylated the C terminus of NHE1 within a 40-amino-acid region. Analysis by mass spectroscopy identified four phosphorylation sites on NHE1, Thr 717, Ser 722, Ser 725, and Ser 728. Thus, loss of trophic cytokine signaling induced the p38 MAPK pathway, which phosphorylated NHE1 at specific sites, inducing intracellular alkalinization.
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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.