ArticleThe Journal of cell biology2013
pH sensing by FAK-His58 regulates focal adhesion remodeling.
Article in The Journal of cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 103 citations in OpenAlex.
- Therapeutic Potential of Allomyrinasin in Oral Squamous Cell Carcinoma via Decreased NBC Activity.Pharmaceutics · 2026Article
- Targeting Cytoskeleton and Cell Motility: Past and Novel Strategies for Cancer Therapy.Oncology research · 2026Review
- Intracellular pH dynamics respond to extracellular matrix stiffening and mediate vasculogenic mimicry through β-catenin.Cell death & disease · 2025Article
- Human Plastins are Novel Cytoskeletal pH Sensors with a Reduced F-actin Bundling Capacity at Basic pH.Journal of molecular biology · 2025Article
- Intracellular pH dynamics respond to extracellular matrix stiffening and mediate vasculogenic mimicry through β-catenin.bioRxiv : the preprint server for biology · 2025Article
- A role for pH dynamics regulating transcription factor DNA-binding selectivity.Nucleic acids research · 2025Article
- Malate initiates a proton-sensing pathway essential for pH regulation of inflammation.Signal transduction and targeted therapy · 2024Article
- Intracellular pH differentially regulates transcription of metabolic and signaling pathways in normal epithelial cells.The Journal of biological chemistry · 2024Article
- Evolution of pH-sensitive transcription termination inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Focal adhesion kinase signaling - tumor vulnerabilities and clinical opportunities.Journal of cell science · 2024Review
- pH-regulated single cell migration.Pflugers Archiv : European journal of physiology · 2024Review
- Evolution of pH-sensitive transcription termination during adaptation to repeated long-term starvation.bioRxiv : the preprint server for biology · 2024Article
- Computational investigation of missense somatic mutations in cancer and potential links to pH-dependence and proteostasis.PloS one · 2024Article
- How protons pave the way to aggressive cancers.Nature reviews. Cancer · 2023Review
- Focal adhesion kinase: from biological functions to therapeutic strategies.Experimental hematology & oncology · 2023Review
- Single-cell intracellular pH dynamics regulate the cell cycle by timing the G1 exit and G2 transition.Journal of cell science · 2023Article
- Targeting Na-H exchanger 1 overcomes nuclear factor kappa B-mediated tumor resistance to radiotherapy.Neoplasia (New York, N.Y.) · 2023Article
- Long non-coding RNAs modulate tumor microenvironment to promote metastasis: novel avenue for therapeutic intervention.Frontiers in cell and developmental biology · 2023Review
- Acidic environments trigger intracellular H+-sensing FAK proteins to re-balance sarcolemmal acid-base transporters and auto-regulate cardiomyocyte pH.Cardiovascular research · 2022Article
- FAK in Cancer: From Mechanisms to Therapeutic Strategies.International journal of molecular sciences · 2022Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Intracellular pH (pHi) dynamics regulates diverse cellular processes, including remodeling of focal adhesions. We now report that focal adhesion kinase (FAK), a key regulator of focal adhesion remodeling, is a pH sensor responding to physiological changes in pH. The initial step in FAK activation is autophosphorylation of Tyr397, which increased with higher pHi. We used a genetically encoded biosensor to show increased pH at focal adhesions as they mature during cell spreading. We also show that cells with reduced pHi had attenuated FAK-pY397 as well as defective cell spreading and focal adhesions. Mutagenesis studies indicated FAK-His58 is critical for pH sensing and molecular dynamics simulations suggested a model in which His58 deprotonation drives conformational changes that may modulate accessibility of Tyr397 for autophosphorylation. Expression of FAK-H58A in fibroblasts was sufficient to restore defective autophosphorylation and cell spreading at low pHi. These data are relevant to understanding cancer metastasis, which is dependent on increased pHi and FAK activity.
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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.