Affinage

PTK2

Focal adhesion kinase 1 · UniProt Q05397

Length
1052 aa
Mass
119.2 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTK2/FAK is a non-receptor tyrosine kinase that integrates integrin and growth-factor-receptor signals at focal adhesions to drive directed cell migration, invasion, and survival (PMID:10806474, PMID:12615911). Adhesion-dependent activation is mediated by its N-terminal FERM domain, which engages activated PDGF- and EGF-receptor complexes and directs assembly at integrin clustering sites, while the C-terminal domain governs focal-adhesion targeting; FERM-domain point mutations abolish in-cell activation and Src-family kinase binding without altering intrinsic catalysis (PMID:10806474, PMID:15169899). Mechanistically, autophosphorylation at Tyr-397 requires local enrichment at focal adhesions that promotes site-specific FERM-mediated dimerization, stabilized by a FERM–FAT interaction and reinforced by paxillin recruitment (PMID:24480479). Tyr-397 phosphorylation and kinase activity are selectively required for invasion through assembly of a FAK–Src–p130Cas–Dock180 complex that activates Rac and JNK and elevates MMP activity, defining an invasion pathway distinct from integrin-stimulated motility (PMID:12615911). FAK also transactivates receptor tyrosine kinases by activation-loop-independent phosphorylation, promoting IGF-1R stability and downstream Akt/ERK signaling and CSF-1R activation during fibronectin-induced migration (PMID:19545541, PMID:27588738). Beyond the cytoplasm, catalytic inhibition forces FAK nuclear localization where it controls protein turnover and transcription, promoting TRAF6-dependent DNMT3A ubiquitination to maintain smooth-muscle differentiation and binding p53 to suppress its transcriptional activity (PMID:34702049, PMID:21355845). FAK phosphorylates a diverse substrate set including HDAC5 (Tyr-642), β-catenin (Tyr-654), and—via ERK1/2—Drp1 to drive mitochondrial fission, and acts upstream of YAP nuclear localization through a talin-binding, catalysis-dependent mechanism (PMID:32612176, PMID:28881682, PMID:34739186, PMID:38547833). FAK signaling is restrained by DUSP22, which dephosphorylates Tyr-397 and Tyr-576/577, and by ARHGAP21 binding to its C-terminal region (PMID:36209205, PMID:19268501).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1999 High

    Established which FAK modules are functionally required for migration, separating kinase activity, the Tyr-397/SH2 site, and SH3-binding regions from dispensable direct paxillin binding.

    Evidence Systematic point/deletion mutant rescue in FAK-null fibroblasts with FRNK dominant-negative and migration assays

    PMID:10413676

    Open questions at the time
    • Did not define how Tyr-397 phosphorylation is triggered upstream
    • Mechanism of FRNK focal-contact localization requirement unresolved
  2. 1999 Medium

    Defined FAK/p130Cas as a directionally persistent migration pathway distinct from Shc/MAPK random motility, placing FAK within a PTEN-regulated migration network.

    Evidence Overexpression epistasis in PTEN-reconstituted U87-MG cells with directionality assays

    PMID:10427092

    Open questions at the time
    • Overexpression-based, single genetic background
    • Molecular link between FAK and directional persistence not detailed
  3. 2000 High

    Showed FAK is a receptor-proximal integrator, with the FERM domain binding activated growth-factor receptors and the C-terminus directing integrin-site targeting.

    Evidence Co-IP, domain-deletion constructs, FAK-null reconstitution, motility assays

    PMID:10806474

    Open questions at the time
    • Structural basis of FERM–receptor binding not resolved
    • Whether transphosphorylation is intermolecular not directly shown
  4. 2003 High

    Distinguished invasion from motility mechanistically by identifying a kinase-dependent FAK–Src–p130Cas–Dock180–Rac–JNK–MMP axis.

    Evidence FAK-null rescue with mutants, v-Src transformation, Co-IP, Rac/JNK assays, MMP zymography, invasion assays

    PMID:12615911

    Open questions at the time
    • Spatial regulation of lamellipodial FAK accumulation not fully defined
    • Direct versus indirect MMP regulation unresolved
  5. 2004 High

    Localized adhesion-dependent activation to a specific FERM-domain sequence required for Src binding and in-cell tyrosine phosphorylation, distinct from intrinsic catalysis.

    Evidence FERM point mutagenesis, in vitro kinase assay, pulldown of FERM–FAK interaction, migration assays

    PMID:15169899

    Open questions at the time
    • Did not show the dimeric/oligomeric nature of activation
    • Conformational change mechanism not yet defined
  6. 2004 Medium

    Identified a kinase-activity-independent regulatory phosphorylation by Cdk5 at Ser-732 controlling centrosomal microtubules and nuclear translocation in neuronal migration.

    Evidence In vitro Cdk5 kinase assay, pS732 antibody, S732A mutant, neuronal migration assays

    PMID:14712065

    Open questions at the time
    • Single lab
    • Effector linking pS732 to centrosomal microtubule structure not identified
  7. 2008 Medium

    Provided a molecular basis for FAK nuclear-cytoplasmic shuttling by mapping two conserved nuclear export signals.

    Evidence NES identification, mutational analysis, nuclear export activity assays

    PMID:18549812

    Open questions at the time
    • Nuclear import mechanism not addressed
    • Physiological triggers of export not defined
  8. 2009 Medium

    Extended FAK function to receptor-tyrosine-kinase transactivation by showing it drives activation-loop-independent IGF-1R phosphorylation and stability.

    Evidence FAK-null vs WT MEFs, siRNA, IGF-1R autophosphorylation mutants, Akt/ERK and stability assays

    PMID:19545541

    Open questions at the time
    • Whether FAK directly phosphorylates IGF-1R not definitively shown
    • Single lab
  9. 2014 High

    Resolved the activation mechanism: Tyr-397 autophosphorylation requires focal-adhesion-enriched, FERM-mediated dimerization stabilized by FERM–FAT contacts and paxillin.

    Evidence X-ray crystallography, SAXS, dimerization and autophosphorylation biochemistry, paxillin interaction and cell assays

    PMID:24480479

    Open questions at the time
    • Dynamics of dimer assembly in live cells not directly captured
    • How force/enrichment is sensed not fully defined
  10. 2013 Medium

    Demonstrated a kinase-independent nuclear function: direct p53 binding that suppresses p53 transcriptional output.

    Evidence Reciprocal Co-IP, pulldown, confocal co-localization, p53 reporter assays, p53 site mutagenesis

    PMID:21355845

    Open questions at the time
    • Single lab
    • Structural detail of the 7-residue interaction surface limited
  11. 2013 Medium

    Identified a FAK–VEGFR-3 complex whose disruption co-inactivates both kinases and suppresses tumor growth, expanding the RTK partner set.

    Evidence Co-IP, small-molecule C4 disruption, phospho-immunoblot, viability/apoptosis assays, murine pancreatic tumor models

    PMID:24142503

    Open questions at the time
    • Directionality of the phosphorylation interdependence unclear
    • Single lab
  12. 2016 Medium

    Linked FAK to anoikis resistance and metastasis downstream of SMARCE1/HIF1A via ERK/AKT and BIM suppression.

    Evidence Co-IP, ChIP, epistatic knockdowns, anoikis assay, xenograft metastasis model

    PMID:27495308

    Open questions at the time
    • How attachment loss triggers PTK2 activation not defined
    • Single lab
  13. 2016 Medium

    Placed FAK in a fibronectin–SFK–FAK–CSF-1R cascade required for macrophage migration.

    Evidence Sequential SFK/FAK/CSF-1R inhibition, Co-IP, genetic and pharmacological approaches, migration assays

    PMID:27588738

    Open questions at the time
    • Whether FAK directly phosphorylates CSF-1R not shown
    • Single lab
  14. 2016 Medium

    Showed FAK is required for FGFR surface expression and FGF signaling during myofibroblast de-differentiation, independent of TGF-β.

    Evidence shRNA and FAK-null MEFs, FGFR surface assay, ERK readouts, α-SMA/stress-fiber quantification

    PMID:16585062

    Open questions at the time
    • Mechanism by which FAK controls FGFR surface levels unresolved
    • Single lab
  15. 2016 Medium

    Revealed a non-cell-autonomous role: stromal FAK loss reprograms cancer-cell metabolism via chemokine–CCR1/CCR2–PKA–glycolysis paracrine signaling.

    Evidence CAF-specific conditional FAK knockout, phosphoproteomics, receptor blockade, PKA and glycolysis assays

    PMID:32157087

    Open questions at the time
    • FAK substrates controlling chemokine output not identified
    • Single lab
  16. 2017 Medium

    Expanded FAK substrate scope in immune signaling, showing LFA-1-activated FAK phosphorylates LAT at Y171 to form de-adhesion complexes.

    Evidence LFA-1 cross-linking, Co-IP, LAT Y171 mutant, FAK kinase assay, T-cell:DC conjugate and proliferation assays

    PMID:28699640

    Open questions at the time
    • Single lab
    • Selectivity over canonical LAT kinases not fully defined
  17. 2017 Medium

    Identified RACK1-scaffolded PDE4D as a FAK partner promoting melanoma invasion.

    Evidence Co-IP of PDE4D–FAK via RACK1, PDE4 inhibition, interaction disruption, invasion assays, in situ analysis

    PMID:28092671

    Open questions at the time
    • Mechanistic effect of PDE4D on FAK activity not defined
    • Single lab
  18. 2019 Medium

    Connected FAK to protein-aggregate clearance: it phosphorylates SQSTM1/p62 at Ser-403 via TBK1, and its inhibition rescues TARDBP proteinopathy.

    Evidence Inhibitor screen, pS403 immunoblot, S403A rescue, TBK1 epistasis, Drosophila TARDBP model

    PMID:31690171

    Open questions at the time
    • Whether FAK acts directly on TBK1 not resolved
    • Single lab
  19. 2020 High

    Established direct FAK phosphorylation of HDAC5 at Tyr-642 controlling its localization and mechanically responsive bone gene regulation.

    Evidence Direct kinase assay, phospho-specific antibody, FAK inhibition in vitro and in vivo, HDAC4/5 translocation imaging, Sost mRNA

    PMID:32612176

    Open questions at the time
    • How shear stress triggers FAK dephosphorylation not detailed
    • Single lab
  20. 2021 Medium

    Defined a nuclear, catalysis-restraining FAK function: catalytic inhibition drives nuclear FAK to promote TRAF6-dependent DNMT3A degradation and maintain SMC differentiation.

    Evidence FAK inhibitors, conditional genetic inhibition, RNA-seq, DNMT3A ubiquitination assays, methylation analysis, TRAF6 manipulation

    PMID:34702049

    Open questions at the time
    • Whether FAK directly ubiquitinates DNMT3A or scaffolds TRAF6 unclear
    • Single lab
  21. 2021 Medium

    Placed FAK upstream of YAP via Tyr-357 phosphorylation in cholangiocarcinoma initiation.

    Evidence Conditional FAK knockout and overexpression mice, FAK inhibitor in cell lines, pY357-YAP immunoblot

    PMID:34052254

    Open questions at the time
    • Directness of YAP phosphorylation by FAK not established
    • Single lab
  22. 2021 Medium

    Identified FAK control of β-catenin Tyr-654 phosphorylation as a cancer-stem-cell-selective vulnerability.

    Evidence FAK inhibitors, pY654-β-catenin immunoblot, constitutively active β-catenin rescue, CSC assays, xenografts

    PMID:28881682

    Open questions at the time
    • Whether FAK directly phosphorylates β-catenin not shown
    • Single lab
  23. 2021 Medium

    Linked FAK to mitochondrial dynamics through a fibronectin–FAK–ERK1/2–Drp1 fission pathway regulating cardiomyocyte respiration.

    Evidence FAK/ERK inhibition, Drp1 phospho-immunoblot, mitochondrial imaging, Seahorse OCR, ATP assays

    PMID:34739186

    Open questions at the time
    • Mechanism of Drp1 mitochondrial recruitment not defined
    • Single lab
  24. 2022 Medium

    Identified DUSP22 as a direct negative regulator dephosphorylating FAK Tyr-397 and Tyr-576/577 to suppress ERK1/2 and NF-κB.

    Evidence Co-IP, phospho-FAK immunoblot, DUSP22 knockout/transgenic mice, AAV gene therapy

    PMID:36209205

    Open questions at the time
    • Direct phosphatase activity inferred rather than reconstituted
    • Single lab
  25. 2024 Medium

    Dissected FAK's mechanotransduction role, showing talin-binding and catalytic activity control YAP nuclear localization independent of nuclear tension and traction forces.

    Evidence Domain-specific FAK mutants, catalytic inhibition, vinculin-talin disruption, YAP localization, traction force microscopy

    PMID:38547833

    Open questions at the time
    • Molecular intermediary between FAK and YAP transport not identified
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the spatial switch between cytoplasmic/focal-adhesion FAK kinase signaling and nuclear kinase-independent functions is coordinated in vivo, and which substrate phosphorylations are direct versus indirect, remains unresolved.
  • Directness of many reported substrate phosphorylations (YAP, β-catenin, CSF-1R, IGF-1R) not established
  • In vivo regulation of nuclear FAK localization incompletely defined
  • Integration of force-sensing with biochemical activation not fully reconstituted

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0060089 molecular transducer activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1474244 Extracellular matrix organization 2
Partners
ARHGAP21BCAR1DUSP22EGFRIGF1RPDGFRAPXNSRC
Complex memberships
FAK-Src-p130Cas-Dock180 invasion complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 FAK associates with activated PDGF- and EGF-receptor signaling complexes via its N-terminal band-4.1-like (FERM) domain, and requires its C-terminal domain for targeting to integrin-receptor clustering sites; kinase-inactive FAK is transphosphorylated at Y397 after EGF stimulation, establishing FAK as a receptor-proximal integrator of growth-factor and integrin signals for cell migration. Co-immunoprecipitation, domain-deletion constructs, FAK-null fibroblast reconstitution, cell motility assays Nature cell biology High 10806474
1999 FAK kinase activity, the Tyr-397/SH2-binding site, and the first proline-rich SH3-binding region in the FAK C-terminal domain are each individually required for full FAK-mediated fibronectin-stimulated cell migration; direct paxillin binding to FAK is not required. The dominant-negative C-terminal fragment FRNK blocks FAK-mediated migration only when localized to focal contacts. FAK-null fibroblast reconstitution with point/deletion mutants, FRNK overexpression, cell migration assays Journal of cell science High 10413676
1999 FAK and p130Cas define a directionally persistent cell-migration pathway that is distinct from a Shc/MAP-kinase-dependent random-motility pathway; both pathways are down-regulated by tumor suppressor PTEN, which directly dephosphorylates Shc. Overexpression of FAK, p130Cas, dominant-negative Shc, and constitutively active MEK1 in PTEN-reconstituted U87-MG cells; migration directionality assays The Journal of cell biology Medium 10427092
2003 FAK Y397 phosphorylation and FAK kinase activity are required for cell invasion but not for integrin-stimulated motility; invasion involves formation of a FAK-Src-p130Cas-Dock180 signaling complex, elevated Rac and JNK activation, and increased MMP expression and activity. Transient FAK accumulation at lamellipodia is linked to the invasive phenotype. FAK-null cells reconstituted with FAK mutants, v-Src transformation, Co-IP of FAK-Src-p130Cas-Dock180 complex, Rac and JNK activity assays, MMP zymography, invasion assays The Journal of cell biology High 12615911
2004 A specific sequence in the FAK FERM domain is required for cell-adhesion-dependent activation of FAK in vivo; point mutations in this sequence reduce tyrosine phosphorylation and Src family kinase binding without affecting intrinsic catalytic activity in vitro. Purified FERM domain interacts directly with full-length FAK in vitro. FERM domain point mutagenesis, in vitro kinase assay, Co-IP/pulldown, cell migration assays Molecular and cellular biology High 15169899
2014 FAK autophosphorylation at Tyr-397 requires site-specific dimerization of FAK mediated by association of the N-terminal FERM domains; dimers are stabilized by a FERM–FAT interaction; paxillin plays a dual role by recruiting FAK to focal adhesions and reinforcing the FAT:FERM interaction; dimerization requires local enrichment at focal adhesions. X-ray crystallography, small-angle X-ray scattering (SAXS), biochemical dimerization assays, FAK autophosphorylation assays, paxillin interaction studies, functional cell-based assays The EMBO journal High 24480479
2008 FAK contains two nuclear export signal (NES) sequences: NES1 in the F1 lobe of the FERM domain and NES2 in the kinase domain; only NES2 demonstrates full biological nuclear export activity. Both are evolutionarily conserved and present in the FAK-related kinase Pyk2. NES sequence identification, mutational analysis, nuclear export activity assays FEBS letters Medium 18549812
2004 Cdk5 phosphorylates FAK at Serine 732 in vitro and in the developing brain; S732 phosphorylation regulates a centrosome-associated microtubule structure to promote nuclear translocation during neuronal migration without directly affecting FAK kinase activity, and prevents accumulation of FAK at the centrosome. In vitro kinase assay (Cdk5 + FAK), phospho-specific antibody (pS732), S732A unphosphorylatable FAK mutant, neuronal migration assays Cell cycle Medium 14712065
2009 FAK mediates activation-loop-independent phosphorylation of IGF-1R, promotes Akt and ERK activation downstream of IGF-1R, and is required for IGF-1R stability; FAK-null MEFs display reduced IGF-1R phosphorylation and stability compared to wild-type MEFs. FAK-null vs wild-type MEFs, FAK siRNA knockdown, autophosphorylation assays with IGF-1R mutants, immunoblot for Akt/ERK, IGF-1R stability assays Biochemical and biophysical research communications Medium 19545541
2020 FAK directly phosphorylates HDAC5 at Tyr-642 in osteocytes, a post-translational modification that controls HDAC5 subcellular localization; fluid-flow shear stress triggers FAK dephosphorylation, promoting HDAC4/5 nuclear translocation and Sost (Sclerostin) suppression for bone formation. Direct phosphorylation assay (FAK + HDAC5), phospho-specific antibody, pharmacological FAK inhibition in vitro and in vivo, HDAC4/5 nuclear translocation imaging, Sost mRNA measurement Nature communications High 32612176
2021 FAK is required for YAP phosphorylation at Tyr-357 in intrahepatic cholangiocarcinoma cells; FAK ablation strongly delayed Akt/YAP-driven iCCA initiation and suppressed tumor progression, establishing FAK as a central upstream regulator of YAP in this context. Conditional FAK knockout mice, FAK overexpression mice, in vitro cell line studies with FAK inhibitor, phospho-Y357 YAP immunoblot Journal of hepatology Medium 34052254
2021 FAK inhibition blocks β-catenin activation by reducing tyrosine-654 phosphorylation of β-catenin, preferentially targeting cancer stem cells; a constitutively active β-catenin mutant reversed FAK-inhibitor-mediated CSC targeting, placing β-catenin downstream of FAK in CSC regulation. FAK inhibitors (VS-4718, VS-6063), immunoblot for pY654-β-catenin, constitutively active β-catenin rescue, CSC assays (tumorsphere, ALDH, limiting dilution), xenograft models Oncotarget Medium 28881682
2017 LFA-1 cross-linking activates FAK1 (PTK2), which phosphorylates LAT at a single site (Y171) to create LAT-GRB2-SKAP1 complexes distinct from canonical LAT-Gads-SLP-76 complexes; these complexes decrease T-cell–DC dwell times and reduce T-cell proliferation, establishing FAK as a mediator of LFA-1-induced T-cell de-adhesion. LFA-1 cross-linking, Co-IP, LAT Y171 mutant, FAK1 kinase assay, T-cell:DC conjugate formation assays, proliferation assays Nature communications Medium 28699640
2019 PTK2/FAK phosphorylates SQSTM1/p62 at Ser-403 via activation of TBK1; inhibition of PTK2 reduced ubiquitin aggregate accumulation and attenuated TARDBP-induced cytotoxicity in neuronal cells, and PTK2 inhibition rescued TARDBP proteinopathy phenotypes in a Drosophila model. Kinase inhibitor screening, immunoblot for pS403-SQSTM1, SQSTM1-S403A non-phosphorylatable mutant rescue, Drosophila TARDBP model, TBK1 co-manipulation Autophagy Medium 31690171
2022 DUSP22 directly interacts with FAK and dephosphorylates FAK at Tyr-397 and Tyr-576/577, thereby suppressing downstream ERK1/2 and NF-κB signaling; disruption of DUSP22-FAK binding abolishes DUSP22-mediated amelioration of NASH progression. Co-IP (DUSP22–FAK interaction), phospho-FAK immunoblot, DUSP22 knockout and transgenic mice, AAV gene therapy, in vitro phosphatase assay implied Nature communications Medium 36209205
2016 FAK depletion in cancer-associated fibroblasts (CAFs) increases chemokine production, which activates CCR1/CCR2 on cancer cells, leading to protein kinase A activation and enhanced malignant cell glycolysis; this paracrine mechanism is independent of genetic mutations in cancer cells. Conditional FAK knockout in CAF subpopulation (mouse model), proteomic/phosphoproteomic analysis, CCR1/CCR2 receptor blocking, PKA activity measurement, glycolysis assays Nature communications Medium 32157087
2021 FAK activation in vascular smooth muscle cells (SMCs) stabilizes DNMT3A in the cytoplasm; pharmacological or genetic FAK catalytic inhibition forces FAK nuclear localization, where nuclear FAK promotes DNMT3A ubiquitination and proteasomal degradation via E3 ligase TRAF6, causing DNA hypomethylation of contractile gene promoters and maintaining SMC differentiation. FAK inhibitors, conditional FAK genetic inhibition, RNA-sequencing of injured femoral arteries, DNMT3A ubiquitination assays, DNA methylation analysis of contractile gene promoters, TRAF6 co-manipulation Circulation research Medium 34702049
2009 ARHGAP21 interacts with the C-terminal region of FAK in glioblastoma cells; ARHGAP21 depletion increases FAK phosphorylation, Cdc42 activity, MMP-2 production, and cell migration, indicating ARHGAP21 negatively regulates FAK signaling. Co-IP (ARHGAP21–FAK), shRNA knockdown of ARHGAP21, immunofluorescence, FAK phosphorylation assay, Cdc42 activity assay, MMP-2 zymography, migration assay Biochimica et biophysica acta Medium 19268501
2017 PDE4D promotes FAK-mediated melanoma invasion by interacting with FAK through the scaffolding protein RACK1; inhibition of PDE4 activity or disruption of PDE4D–FAK interaction reduces invasion; PDE4D–FAK interaction is detectable in situ in metastatic melanoma. Co-IP (PDE4D–FAK via RACK1), PDE4 inhibition, disruption of PDE4D–FAK interaction, invasion assays, in situ analysis Oncogene Medium 28092671
2013 FAK directly interacts with p53 in both cytoplasm and nucleus; FAK inhibits p53 transcriptional activity (p21, Bax, Mdm-2 targets) through protein–protein interaction; a 7-amino-acid site on p53 mediates the interaction with FAK. Co-immunoprecipitation, pulldown assay, confocal microscopy co-localization, p53 transcriptional reporter assays, site-directed mutagenesis of p53 Anti-cancer agents in medicinal chemistry Medium 21355845
2021 FAK regulates Drp1 phosphorylation and mitochondrial Drp1 levels in cardiomyocytes; extracellular fibronectin activates the FAK-ERK1/2-Drp1 pathway to promote mitochondrial fission, increase oxygen consumption rate and ATP production; adrenergic agonists also activate this pathway to stimulate cardiomyocyte respiration. FAK inhibition, ERK1/2 inhibition, Drp1 phosphorylation immunoblot, mitochondrial morphology imaging, oxygen consumption rate (Seahorse), ATP assay in neonatal rat ventricular myocytes The FEBS journal Medium 34739186
2024 Disruption of the talin-binding site on FAK or elimination of FAK catalytic activity prevents YAP nuclear localization and transcriptional activity without altering nuclear size or traction forces, whereas disruption of vinculin-talin binding reduces nuclear size and traction forces before affecting YAP; this defines a nuclear-tension-independent mechanism by which FAK controls YAP nuclear localization. Domain-specific FAK mutants (talin-binding site), FAK catalytic inhibition, vinculin-talin interaction disruption, YAP nuclear localization quantification, traction force microscopy, nuclear size measurement in fibroblasts and hMSCs on deformable substrates Biomaterials Medium 38547833
2016 SMARCE1 interacts with and potentiates HIF1A transcriptional activity upon loss of cell attachment, resulting in rapid PTK2/FAK activation; PTK2 and HIF1A are each required for SMARCE1-mediated anoikis resistance, acting through ERK/AKT activation and BIM suppression. Co-IP (SMARCE1–HIF1A), ChIP assay, SMARCE1/HIF1A/PTK2 knockdown, anoikis assay, ERK/AKT/BIM immunoblot, xenograft lung metastasis model Breast cancer research Medium 27495308
2016 Fibronectin induces macrophage migration through a signaling pathway in which SFK activity is required upstream of FAK activation, and FAK in turn drives ligand-independent phosphorylation and activation of CSF-1R (c-FMS); both FAK and CSF-1R are required for FN-induced macrophage migration. FAK phosphorylation immunoblot, SFK/FAK inhibitors, CSF-1R genetic knockdown and pharmacological inhibition, Co-IP (CSF-1R–β1 integrin interaction), migration assays in murine and human macrophages Cell adhesion & migration Medium 27588738
2013 FAK directly interacts with VEGFR-3 in cancer cells; disruption of this interaction with small molecule C4 causes dephosphorylation of both VEGFR-3 and FAK, reduces cell viability, causes cell-cycle arrest and apoptosis, and reduces tumor growth in murine pancreatic cancer models. Co-IP (FAK–VEGFR-3), small molecule C4 disruption, phospho-FAK/VEGFR-3 immunoblot, cell viability/apoptosis assays, subcutaneous and orthotopic murine tumor models Oncotarget Medium 24142503
2016 FAK is required for FGF/heparin-mediated down-regulation of smooth muscle alpha-actin (myofibroblast de-differentiation); FAK-null MEFs show reduced FGFR surface expression and FGF signaling, establishing FAK as necessary for FGF signal transduction but not for TGF-β-dependent myofibroblast differentiation. FAK shRNA knockdown, FAK-/- MEFs, FGFR surface expression assay, FGF signaling readouts (ERK), alpha-SMA immunostaining, stress fiber quantification FASEB journal Medium 16585062

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 FAK in cancer: mechanistic findings and clinical applications. Nature reviews. Cancer 1118 25098269
2000 FAK integrates growth-factor and integrin signals to promote cell migration. Nature cell biology 1079 10806474
1999 Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration. Journal of cell science 571 10413676
2003 Differential regulation of cell motility and invasion by FAK. The Journal of cell biology 453 12615911
1999 Shc and FAK differentially regulate cell motility and directionality modulated by PTEN. The Journal of cell biology 368 10427092
2004 Multiple connections link FAK to cell motility and invasion. Current opinion in genetics & development 350 15108811
2014 FAK signaling in human cancer as a target for therapeutics. Pharmacology & therapeutics 348 25316657
2021 Targeting FAK in anticancer combination therapies. Nature reviews. Cancer 315 33731845
2010 The FERM domain: organizing the structure and function of FAK. Nature reviews. Molecular cell biology 298 20966971
2018 Addressing Kinase-Independent Functions of Fak via PROTAC-Mediated Degradation. Journal of the American Chemical Society 238 30444612
2019 The roles of nuclear focal adhesion kinase (FAK) on Cancer: a focused review. Journal of experimental & clinical cancer research : CR 230 31186061
2000 Pyk2 and FAK regulate neurite outgrowth induced by growth factors and integrins. Nature cell biology 184 10980697
2020 FAK Structure and Regulation by Membrane Interactions and Force in Focal Adhesions. Biomolecules 163 31991559
2014 Targeting FAK in human cancer: from finding to first clinical trials. Frontiers in bioscience (Landmark edition) 158 24389213
2022 FAK in Cancer: From Mechanisms to Therapeutic Strategies. International journal of molecular sciences 139 35163650
2020 Cancer associated fibroblast FAK regulates malignant cell metabolism. Nature communications 124 32157087
2019 Highly Selective PTK2 Proteolysis Targeting Chimeras to Probe Focal Adhesion Kinase Scaffolding Functions. Journal of medicinal chemistry 111 30739444
2008 FERM control of FAK function: implications for cancer therapy. Cell cycle (Georgetown, Tex.) 111 18677107
2014 FAK dimerization controls its kinase-dependent functions at focal adhesions. The EMBO journal 106 24480479
2011 Focal adhesion kinase: exploring Fak structure to gain insight into function. International review of cell and molecular biology 106 21482413
2017 FAK inhibitors in Cancer, a patent review. Expert opinion on therapeutic patents 98 29210300
2003 PTK2 and EIF3S3 genes may be amplification targets at 8q23-q24 and are associated with large hepatocellular carcinomas. Hepatology (Baltimore, Md.) 97 14578863
2004 FERM domain interaction promotes FAK signaling. Molecular and cellular biology 96 15169899
2021 Focal adhesion kinase (FAK) promotes cholangiocarcinoma development and progression via YAP activation. Journal of hepatology 95 34052254
2021 Discovery and Characterisation of Highly Cooperative FAK-Degrading PROTACs. Angewandte Chemie (International ed. in English) 91 34416073
2016 Endosomes: Emerging Platforms for Integrin-Mediated FAK Signalling. Trends in cell biology 89 26944773
2016 FAK and paxillin, two potential targets in pancreatic cancer. Oncotarget 84 26980710
2013 The role of FAK in tumor metabolism and therapy. Pharmacology & therapeutics 84 24333503
2013 Nuclear FAK: a new mode of gene regulation from cellular adhesions. Molecules and cells 82 23686429
2003 FAK signaling in anaplastic astrocytoma and glioblastoma tumors. Cancer journal (Sudbury, Mass.) 82 12784878
2020 FAK-Dependent Cell Motility and Cell Elongation. Cells 79 31940873
2020 Progress in the Development of Small Molecular Inhibitors of Focal Adhesion Kinase (FAK). Journal of medicinal chemistry 76 33058670
2020 A FAK/HDAC5 signaling axis controls osteocyte mechanotransduction. Nature communications 75 32612176
2010 TGF-ß1 and FAK regulate periostin expression in PDL fibroblasts. Journal of dental research 70 20940356
2006 FAK-dependent regulation of myofibroblast differentiation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 70 16585062
2024 Roles and inhibitors of FAK in cancer: current advances and future directions. Frontiers in pharmacology 65 38410129
2021 Drug Discovery Targeting Focal Adhesion Kinase (FAK) as a Promising Cancer Therapy. Molecules (Basel, Switzerland) 65 34299525
2017 Inhibition of FAK kinase activity preferentially targets cancer stem cells. Oncotarget 62 28881682
2006 FAK signaling in neoplastic disorders: a linkage between inflammation and cancer. Annals of the New York Academy of Sciences 62 17185517
2016 Proteomic Profiling Identifies PTK2/FAK as a Driver of Radioresistance in HPV-negative Head and Neck Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 61 27036135
2017 FAK signalling controls insulin sensitivity through regulation of adipocyte survival. Nature communications 60 28165007
2021 Focal Adhesion Kinase (FAK) Inhibition Synergizes with KRAS G12C Inhibitors in Treating Cancer through the Regulation of the FAK-YAP Signaling. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 59 34151545
2016 Fibronectin induces macrophage migration through a SFK-FAK/CSF-1R pathway. Cell adhesion & migration 59 27588738
2022 New insights into FAK structure and function in focal adhesions. Journal of cell science 58 36239192
2004 Regulation of endothelial cell function BY FAK and PYK2. Frontiers in bioscience : a journal and virtual library 58 14977542
2012 β1 integrin-focal adhesion kinase (FAK) signaling modulates retinal ganglion cell (RGC) survival. PloS one 57 23118988
2008 Clinical significance of FAK expression in human neoplasia. Histology and histopathology 55 18283648
2008 FAK nuclear export signal sequences. FEBS letters 55 18549812
2014 Focal adhesion kinase (FAK) perspectives in mechanobiology: implications for cell behaviour. Cell and tissue research 54 24988914
2022 Hepatocyte phosphatase DUSP22 mitigates NASH-HCC progression by targeting FAK. Nature communications 53 36209205
2004 The Escherichia coli fadK (ydiD) gene encodes an anerobically regulated short chain acyl-CoA synthetase. The Journal of biological chemistry 53 15213221
2008 FAK expression regulation and therapeutic potential. Advances in cancer research 50 19055942
2020 FAK Family Kinases in Vascular Diseases. International journal of molecular sciences 48 32455571
2011 Role of FAK in S1P-regulated endothelial permeability. Microvascular research 47 21925517
2011 Endothelial FAK as a therapeutic target in disease. Microvascular research 47 22008516
2021 Kras-driven intratumoral heterogeneity triggers infiltration of M2 polarized macrophages via the circHIPK3/PTK2 immunosuppressive circuit. Scientific reports 46 34326381
2019 PTK2/FAK regulates UPS impairment via SQSTM1/p62 phosphorylation in TARDBP/TDP-43 proteinopathies. Autophagy 46 31690171
2024 FAK, vinculin, and talin control mechanosensitive YAP nuclear localization. Biomaterials 45 38547833
2023 HMGB1-mediated elevation of KLF7 facilitates hepatocellular carcinoma progression and metastasis through upregulating TLR4 and PTK2. Theranostics 45 37554278
2009 ARHGAP21 modulates FAK activity and impairs glioblastoma cell migration. Biochimica et biophysica acta 44 19268501
1999 Why do so many stimuli induce tyrosine phosphorylation of FAK? BioEssays : news and reviews in molecular, cellular and developmental biology 43 10580994
2016 SMARCE1 regulates metastatic potential of breast cancer cells through the HIF1A/PTK2 pathway. Breast cancer research : BCR 39 27495308
2022 Overexpression of BACH1 mediated by IGF2 facilitates hepatocellular carcinoma growth and metastasis via IGF1R and PTK2. Theranostics 38 35154476
2022 HGF-mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c-MET. Journal of experimental & clinical cancer research : CR 38 36109787
2011 FAK and p53 protein interactions. Anti-cancer agents in medicinal chemistry 38 21355845
2013 FAK-heterozygous mice display enhanced tumour angiogenesis. Nature communications 37 23799510
2024 Targeting focal adhesion kinase (FAK) for cancer therapy: FAK inhibitors, FAK-based dual-target inhibitors and PROTAC degraders. Biochemical pharmacology 36 38685282
2021 FAK Activation Promotes SMC Dedifferentiation via Increased DNA Methylation in Contractile Genes. Circulation research 36 34702049
2012 Endothelial paxillin and focal adhesion kinase (FAK) play a critical role in neutrophil transmigration. European journal of immunology 36 22095445
2023 Focal adhesion kinase (FAK): its structure, characteristics, and signaling in skeletal system. Cellular signalling 34 37586468
2018 FAK regulates epithelial‑mesenchymal transition in adenomyosis. Molecular medicine reports 33 30365102
2022 New Insights on the Nuclear Functions and Targeting of FAK in Cancer. International journal of molecular sciences 32 35216114
2009 Focal adhesion kinase (FAK) activates and stabilizes IGF-1 receptor. Biochemical and biophysical research communications 32 19545541
2004 Cdk5 phosphorylation of FAK regulates centrosome-associated miocrotubules and neuronal migration. Cell cycle (Georgetown, Tex.) 32 14712065
2017 LFA-1 activates focal adhesion kinases FAK1/PYK2 to generate LAT-GRB2-SKAP1 complexes that terminate T-cell conjugate formation. Nature communications 31 28699640
2011 FAK: dynamic integration of guidance signals at the growth cone. Cell adhesion & migration 31 20953136
2017 PDE4D promotes FAK-mediated cell invasion in BRAF-mutated melanoma. Oncogene 30 28092671
2016 Osteogenesis requires FAK-dependent collagen synthesis by fibroblasts and osteoblasts. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 27881487
2020 Involvement of the FAK Network in Pathologies Related to Altered Mechanotransduction. International journal of molecular sciences 28 33322030
2019 Simulated microgravity inhibits the viability and migration of glioma via FAK/RhoA/Rock and FAK/Nek2 signaling. In vitro cellular & developmental biology. Animal 28 30820814
2021 CircC16orf62 promotes hepatocellular carcinoma progression through the miR-138-5p/PTK2/AKT axis. Cell death & disease 27 34108451
2007 Focal adhesion kinase (FAK) expression and activation during lens development. Molecular vision 27 17417603
1995 Mapping of the focal adhesion kinase (Fadk) gene to mouse chromosome 15 and human chromosome 8. Mammalian genome : official journal of the International Mammalian Genome Society 27 7766995
2016 Simultaneous deactivation of FAK and Src improves the pathology of hypertrophic scar. Scientific reports 26 27181267
2014 Fangchinoline as a kinase inhibitor targets FAK and suppresses FAK-mediated signaling pathway in A549. Journal of drug targeting 26 25539072
2003 Roles of FAK family kinases in nervous system. Frontiers in bioscience : a journal and virtual library 26 12700130
2024 Targeting focal adhesion kinase (FAK) in cancer therapy: A recent update on inhibitors and PROTAC degraders. European journal of medicinal chemistry 25 39029337
2021 FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro. Biomolecules 25 34827680
2013 FAK and Nanog cross talk with p53 in cancer stem cells. Anti-cancer agents in medicinal chemistry 25 22934707
2013 The FAK scaffold inhibitor C4 disrupts FAK-VEGFR-3 signaling and inhibits pancreatic cancer growth. Oncotarget 25 24142503
2003 PYK2 and FAK in osteoclasts. Frontiers in bioscience : a journal and virtual library 23 12957821
2014 New insights into FAK function and regulation during spermatogenesis. Histology and histopathology 22 24578181
2022 CircRPAP2 regulates the alternative splicing of PTK2 by binding to SRSF1 in breast cancer. Cell death discovery 21 35368030
2021 FAK regulates cardiomyocyte mitochondrial fission and function through Drp1. The FEBS journal 21 34739186
2009 Focal adhesion kinase (FAK) expression in normal and neoplastic lymphoid tissues. Pathology, research and practice 21 19647948
2003 [Focal adhesion kinase (FAK), a multifunctional protein]. Medecine sciences : M/S 21 12942446
2023 Dual roles of FAK in tumor angiogenesis: A review focused on pericyte FAK. European journal of pharmacology 20 36967077
2017 CKAP2 Promotes Ovarian Cancer Proliferation and Tumorigenesis Through the FAK-ERK Pathway. DNA and cell biology 20 28933561
2013 Inhibition of FAK and VEGFR-3 binding decreases tumorigenicity in neuroblastoma. Molecular carcinogenesis 20 23868727
2021 New Insights on Fak and Fak Inhibitors. Current medicinal chemistry 19 33143618

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