ArticleProceedings of the National Academy of Sciences of the United States of America2014
Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion kinase by inducing clustering and conformational changes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
90 citing papers in PubMed, 137 citations in OpenAlex.
- Spatial organization of phosphoinositide signaling.FEBS letters · 2026Review
- Synergistic effect of PIPBiophysical journal · 2026Article
- Molecular basis and cellular effects of Janus-class-driven cytoplasmic PYK2 coacervates.Communications biology · 2026Article
- PIP5K-Ras bistability triggers plasma membrane symmetry breaking to define cellular polarity and regulate migration.bioRxiv : the preprint server for biology · 2025Article
- Focal Adhesion Kinase Intersects With the BRD4-MYC Axis and YAP1 to Drive Tumor Cell Growth, Phenotypic Plasticity, Stemness, and Metastatic Potential in Colorectal Cancer.Cancer medicine · 2025Article
- Targeting the hydrophobic pockets of FAK/PYK2 FAT domain: a highly effective inhibitory strategy suppressing tumor growth and eliminating metastasis.Cell communication and signaling : CCS · 2025Article
- Phospho-regulated tethering of focal adhesion kinase to vinculin links force transduction to focal adhesion signaling.Cell communication and signaling : CCS · 2025Article
- Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.Biomarker research · 2025Review
- Myosin-based nucleation of actin filaments contributes to stereocilia development critical for hearing.Nature communications · 2025Article
- Extracellular Silica Nanomatrices Promote In Vitro Maturation of Anti-tumor Dendritic Cells via Activation of Focal Adhesion Kinase.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- Article
- Focal adhesion kinase signaling - tumor vulnerabilities and clinical opportunities.Journal of cell science · 2024Review
- Molecularly imprinted nanoparticles reveal regulatory scaffolding features in Pyk2 tyrosine kinase.RSC chemical biology · 2024Article
- The phosphatidylinositol-5' phosphatase synaptojanin1 limits integrin-mediated invasion ofMicrobiology spectrum · 2024Article
- FAK Family Kinases: A Potential Therapeutic Target for Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Polarized focal adhesion kinase activity within a focal adhesion during cell migration.Nature chemical biology · 2023Article
- 17β-Estradiol Mediates Staphylococcus aureus Adhesion in Vaginal Epithelial Cells via Estrogen Receptor α-Associated Signaling Pathway.Current microbiology · 2023Article
- Focal adhesion kinase: from biological functions to therapeutic strategies.Experimental hematology & oncology · 2023Review
- On the Value of In Vitro Cell Systems for Mechanobiology from the Perspective of Yes-Associated Protein/Transcriptional Co-Activator with a PDZ-Binding Motif and Focal Adhesion Kinase and Their Involvement in Wound Healing, Cancer, Aging, and Senescence.International journal of molecular sciences · 2023Review
- Impaired activity and membrane association of most calpain-5 mutants causal for neovascular inflammatory vitreoretinopathy.Biochimica et biophysica acta. Molecular basis of disease · 2023Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
Abstract
Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase (NRTK) with key roles in integrating growth and cell matrix adhesion signals, and FAK is a major driver of invasion and metastasis in cancer. Cell adhesion via integrin receptors is well known to trigger FAK signaling, and many of the players involved are known; however, mechanistically, FAK activation is not understood. Here, using a multidisciplinary approach, including biochemical, biophysical, structural, computational, and cell biology approaches, we provide a detailed view of a multistep activation mechanism of FAK initiated by phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. Interestingly, the mechanism differs from canonical NRTK activation and is tailored to the dual catalytic and scaffolding function of FAK. We find PI(4,5)P2 induces clustering of FAK on the lipid bilayer by binding a basic region in the regulatory 4.1, ezrin, radixin, moesin homology (FERM) domain. In these clusters, PI(4,5)P2 induces a partially open FAK conformation where the autophosphorylation site is exposed, facilitating efficient autophosphorylation and subsequent Src recruitment. However, PI(4,5)P2 does not release autoinhibitory interactions; rather, Src phosphorylation of the activation loop in FAK results in release of the FERM/kinase tether and full catalytic activation. We propose that PI(4,5)P2 and its generation in focal adhesions by the enzyme phosphatidylinositol 4-phosphate 5-kinase type Iγ are important in linking integrin signaling to FAK activation.
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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.