ArticleThe Journal of biological chemistry2011
B-Raf associates with and activates the NHE1 isoform of the Na+/H+ exchanger.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 38 citations in OpenAlex.
- BAP1 inactivation promotes lactate production by leveraging the subcellular localization of LDHA in melanoma.Cell death discovery · 2024Article
- Acid-base transporters in the context of tumor heterogeneity.Pflugers Archiv : European journal of physiology · 2024Review
- Amino Acids 785, 787 of the NaInternational journal of molecular sciences · 2021Article
- Hypoxia and Extracellular Acidification as Drivers of Melanoma Progression and Drug Resistance.Cells · 2021Review
- Role of Genetic Mutations of the NaMolecular and cellular biochemistry · 2021Review
- Cancer and pH Dynamics: Transcriptional Regulation, Proteostasis, and the Need for New Molecular Tools.Cancers · 2020Review
- The impact of tumour pH on cancer progression: strategies for clinical intervention.Exploration of targeted anti-tumor therapy · 2020Review
- Structural and Functional Changes in the NaInternational journal of molecular sciences · 2019Review
- MMP3 activity rather than cortical stiffness determines NHE1-dependent invasiveness of melanoma cells.Cancer cell international · 2019Article
- β-Raf activation of the myocardial NaChannels (Austin, Tex.) · 2017Article
- The human Na(+)/H(+) exchanger 1 is a membrane scaffold protein for extracellular signal-regulated kinase 2.BMC biology · 2016Article
- Stop Codon Polymorphisms in the Human SLC9A1 Gene Disrupt or Compromise Na+/H+ Exchanger Function.PloS one · 2016Article
- Upregulation of NHE1 protein expression enables glioblastoma cells to escape TMZ-mediated toxicity via increased H⁺ extrusion, cell migration and survival.Carcinogenesis · 2014Article
- Role of pHi, and proton transporters in oncogene-driven neoplastic transformation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2014Review
- Potential role of sodium-proton exchangers in the low concentration arsenic trioxide-increased intracellular pH and cell proliferation.PloS one · 2012Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The serine/threonine kinase B-Raf is the second most frequently occurring human oncogene after Ras. Mutations of B-Raf occur with the highest incidences in melanoma, and the most common mutant, V600E, renders B-Raf constitutively active. The sodium proton exchanger isoform 1 (NHE1) is a ubiquitously expressed plasma membrane protein responsible for regulating intracellular pH, cell volume, cell migration, and proliferation. A screen of protein kinases that bind to NHE1 revealed that B-Raf bound to the cytosolic regulatory tail of NHE1. Immunoprecipitation of NHE1 from HeLa and HEK cells confirmed the association of B-Raf with NHE1 in vivo. The expressed and purified C-terminal 182 amino acids of the NHE1 protein were also shown to associate with B-Raf protein in vitro. Because treatment with the kinase inhibitor sorafenib decreased NHE1 activity in HeLa and HEK cells, we examined the role of B-Raf in regulating NHE1 in malignant melanoma cells. Melanoma cells with the B-Raf(V600E) mutation demonstrated increased resting intracellular pH that was dependent on elevated NHE1 activity. NHE1 activity after an acute acid load was also elevated in these cell lines. Moreover, inhibition of B-Raf activity by either sorafenib, PLX4720, or siRNA reduction of B-Raf levels abolished ERK phosphorylation and decreased NHE1 activity. These results demonstrate that B-Raf associates with and stimulates NHE1 activity and that B-Raf(V600E) also increases NHE1 activity that raises intracellular pH.
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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 Socratic graph.