ArticleProceedings of the National Academy of Sciences of the United States of America2019
Structural and mechanistic insights into mechanoactivation of focal adhesion kinase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- A comprehensive meta-analysis of transcriptome data to identify signature genes associated with pancreatic ductal adenocarcinoma.PloS one · 2024Pooled it
- Cells perceive the distribution differences of adhesion ligands and consequently establish cellular polarization to regulate osteogenic differentiation.Bioactive materials · 2026Article
- Actin cytoskeletal dynamics in hepatic myofibroblasts and fibrosis.Nature reviews. Gastroenterology & hepatology · 2026Review
- Heat shock transcription factor 1 acts as an endogenous protective mechanism in mechanically stretched alveolar epithelial cells.Cell stress & chaperones · 2026Article
- CD98hc controls CNS angiogenesis and blood-brain barrier integrity through localized regulation of the systemic integrin-FAK pathway.Nature cardiovascular research · 2026Article
- Disarming cancer resistance: FAK as a therapeutic target.Trends in cancer · 2026Review
- Framework for Quantifying the Efficiency of Competing Signal Transmission Modes in Proteins.Journal of the American Chemical Society · 2026Article
- Targeting focal adhesion kinase inhibits cell migration and non-angiogenic vascularization in malignant breast cancer.Breast cancer (Tokyo, Japan) · 2026Article
- N-cadherin-mimetic 3D hydrogels program pro-regenerative and immunomodulatory states in human adipose-derived mesenchymal stem cells.Scientific reports · 2025Article
- Mechanical Signaling: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Bioenergetic responses to β-adrenergic stimulation in beige adipocyte depend on actomyosin driven forces.bioRxiv : the preprint server for biology · 2025Article
- Mechanochemical waves in focal adhesions during cell migration.Science advances · 2025Article
- High-rate mechano-stimulation alters proliferation- and maturation-related signaling of oligodendrocyte precursor cells in a 3D hydrogel.Mechanobiology in medicine · 2025Article
- Mechanochemistry: Fundamental Principles and Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Hyperglycemic state and fluid shear stress affect metastatic breast cancer cell migration via focal adhesion kinase.bioRxiv : the preprint server for biology · 2025Article
- Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.Biomarker research · 2025Review
- Development of attenuated Orf virus as a safe oncolytic viral vector for nasopharyngeal carcinoma treatment.Virology journal · 2025Article
- Transcriptomic analysis reveals impaired tight junction and upregulated IL-17 signaling in induced abnormal keratinization area of rumen.Journal of animal science · 2025Article
- Integrin force loading rate in mechanobiology: From model to molecular measurement.QRB discovery · 2025Review
- Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Focal adhesion kinase (FAK) is a key signaling molecule regulating cell adhesion, migration, and survival. FAK localizes into focal adhesion complexes formed at the cytoplasmic side of cell attachment to the ECM and is activated after force generation via actomyosin fibers attached to this complex. The mechanism of translating mechanical force into a biochemical signal is not understood, and it is not clear whether FAK is activated directly by force or downstream to the force signal. We use experimental and computational single-molecule force spectroscopy to probe the mechanical properties of FAK and examine whether force can trigger activation by inducing conformational changes in FAK. By comparison with an open and active mutant of FAK, we are able to assign mechanoactivation to an initial rupture event in the low-force range. This activation event occurs before FAK unfolding at forces within the native range in focal adhesions. We are also able to assign all subsequent peaks in the force landscape to partial unfolding of FAK modules. We show that binding of ATP stabilizes the kinase domain, thereby altering the unfolding hierarchy. Using all-atom molecular dynamics simulations, we identify intermediates along the unfolding pathway, which provide buffering to allow extension of FAK in focal adhesions without compromising functionality. Our findings strongly support that forces in focal adhesions applied to FAK via known interactions can induce conformational changes, which in turn, trigger focal adhesion signaling.
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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.