Affinage

ILK

Scaffold protein ILK · UniProt Q13418

Length
452 aa
Mass
51.4 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 25 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

ILK is the central scaffold of integrin-based focal adhesions, linking the cytoplasmic tails of integrins to the actin cytoskeleton and coordinating adhesion-dependent signaling, cell spreading, migration, and tissue morphogenesis (PMID:12670870, PMID:30367047). Despite its kinase-like domain, ILK is a bona fide pseudokinase: recombinant ILK has no detectable activity toward GSK-3beta, no specific substrate emerged from whole-cell screens, and its crystal structure shows a degraded pseudo-active site, with the 'kinase-dead' K220M mutation impairing structural integrity rather than catalysis (PMID:21524996). Consistent with this, in vivo knockout and rescue experiments establish that ILK functions through its adaptor role rather than catalytic activity — kinase-inactive ILK fully rescues C. elegans pat-4 nulls and restores actin organization, spreading, and focal adhesion formation in ILK-null fibroblasts (PMID:12015115, PMID:12670870). ILK assembles the heterotrimeric IPP complex by recruiting PINCH through its ankyrin repeat domain and Parvin, and triggers F-actin bundling via WH2 motifs contributed by PINCH and Parvin, a process sensitized by Mg-ATP bound in the pseudoactive site (PMID:12167643, PMID:30367047). ILK additionally engages paxillin through a C-terminal paxillin-binding subdomain required for focal adhesion targeting (PMID:11304546) and binds kindlin-2 on the C-lobe of its pseudokinase domain to support adhesion localization and spreading (PMID:30254023). Through ELMO2–RhoG complexes ILK orients microtubule plus-ends and regulates microtubule dynamics, contributing to epithelial lumen formation and keratinocyte polarity (PMID:19460343, PMID:23263281, PMID:25995380). ILK loss/perturbation is propagated into downstream signaling including PKB/Akt Ser473 and GSK-3beta phosphorylation, HIF-1alpha/VEGF-driven angiogenesis, mTORC2 (Rictor) coupling to TGF-beta-induced EMT, and regulation of VEGFR3–beta1 integrin interaction in lymphatic vessel growth (PMID:14551191, PMID:14749128, PMID:22310280, PMID:30518533). ILK missense variants in the ankyrin repeat domain are associated with arrhythmogenic cardiomyopathy and disrupt the ILK–PINCH complex (PMID:30802431).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1997 Medium

    Establishing the human genomic locus of ILK provided the foundation for subsequent functional and disease-association studies.

    Evidence FISH mapping on metaphase chromosomes and chromatin fibers

    PMID:9177792

    Open questions at the time
    • No functional or mechanistic information from mapping alone
    • Does not address protein activity or partners
  2. 2001 High

    The question of how ILK is targeted to focal adhesions was answered by mapping a direct paxillin-binding subdomain required for localization.

    Evidence In vitro binding, reciprocal Co-IP, and PBS point mutants with GFP-ILK localization in fibroblasts

    PMID:11304546

    Open questions at the time
    • Does not establish whether paxillin binding is sufficient or only necessary
    • Functional consequences downstream of localization not resolved here
  3. 2002 High

    Genetic and biochemical work resolved whether ILK acts as a catalytic enzyme or a structural adaptor by showing kinase-dead ILK fully rescues null worms and by identifying core complex partners.

    Evidence C. elegans pat-4 null genetics with kinase-dead rescue, recruitment epistasis, and PINCH-2 LIM1 Co-IP/deletion mapping in mammalian cells

    PMID:12015115 PMID:12167643

    Open questions at the time
    • Mutually exclusive PINCH-1/PINCH-2 binding consequence in vivo unclear
    • Did not directly test catalytic activity biochemically
  4. 2003 High

    In vivo knockout established that ILK's essential adaptor function in actin organization and embryonic polarity is kinase-independent, and that IPP components are mutually stabilized.

    Evidence Conditional mouse knockout with kinase-dead and paxillin-binding-defective rescue; RNAi of PINCH-1/ILK/alpha-parvin with proteasome inhibition and Akt phospho-readouts

    PMID:12670870 PMID:14551191

    Open questions at the time
    • Mechanism linking ILK to selective Ser473 (not Thr308) Akt phosphorylation not defined
    • Direct molecular basis of mutual protein stabilization unresolved
  5. 2004 Medium

    Multiple studies connected ILK to adhesion-type-specific assembly and to angiogenic and substrate-specific signaling outputs, though catalytic claims relied on immune-complex assays.

    Evidence RNAi in endothelial cells (fibrillar adhesions, capillary morphogenesis); ILKAP/PP2C Co-IP and immune-complex kinase assay; siRNA/inhibitor analysis of HIF-1alpha/VEGF angiogenesis

    PMID:14749128 PMID:14990992 PMID:15316070

    Open questions at the time
    • Immune-complex kinase activity later shown not to reflect intrinsic ILK catalysis
    • GSK-3beta and HIF-1alpha effects could be indirect/scaffold-mediated
  6. 2005 Medium

    Overexpression and dominant-negative studies linked ILK to PI3K-dependent Akt/Rac1 activation driving actin remodeling, migration, and invasion.

    Evidence ILK overexpression and dominant-negative mutants, Rac1 activity assay, PI3K inhibition, migration/invasion assays

    PMID:15735674

    Open questions at the time
    • Overexpression may not reflect physiological stoichiometry
    • Direct versus indirect contribution to Rac1 activation unresolved
  7. 2006 Medium

    Smooth muscle studies attributed contractile signaling (CPI-17/MLC20 phosphorylation) to ILK using kinase-dead R211A, framing ILK as catalytically active.

    Evidence ILK(R211A) dominant-negative and siRNA, kinase assays, contraction and phosphorylation measurements

    PMID:16472257

    Open questions at the time
    • Catalytic interpretation conflicts with later pseudokinase evidence
    • R211A effects may reflect scaffold disruption rather than lost catalysis
  8. 2007 Medium

    Epistasis in polarizing neurons placed ILK between PI3K and Akt/GSK-3beta in axon specification, extending its role to neuronal polarity.

    Evidence ILK inhibitors, kinase-inactive and hyperactive mutants, siRNA, epistasis with PI3K/Akt/GSK-3beta, immunofluorescence

    PMID:17490631

    Open questions at the time
    • Hyperactive-mutant phenotype hard to reconcile with pseudokinase model
    • Molecular mechanism of axon-tip enrichment not defined
  9. 2008 Medium

    Identification of Rsu-1 within the PINCH1-ILK complex and its loss upon Ras transformation linked the IPP scaffold to oncogenic signaling.

    Evidence Co-IP, co-localization, MEK inhibition, siRNA, migration assays in transformed and non-transformed cells

    PMID:18436335

    Open questions at the time
    • Direct versus indirect Rsu-1 binding to ILK not resolved
    • Functional consequence of Rsu-1 loss for adhesion incompletely defined
  10. 2009 Medium

    ELMO2/RhoG and thymosin-beta4 were defined as ILK partners coupling leading-edge actin polymerization to Akt2 activation and MMP-2-mediated matrix degradation.

    Evidence FRET, Co-IP, spatial localization, Akt2 activation and MMP-2 assays

    PMID:19460343

    Open questions at the time
    • Stoichiometry and architecture of the tripartite ERI complex not structurally defined
    • Whether Tbeta4-ILK signaling requires the IPP complex unclear
  11. 2011 High

    Rigorous reconstitution, proteomics, and crystallography resolved the long-standing catalytic controversy by establishing ILK as a bona fide pseudokinase and reinterpreting kinase-dead mutations as structural.

    Evidence Recombinant in vitro kinase assays, whole-cell substrate proteomics, X-ray crystallography, thermodynamic stability, mutagenesis

    PMID:21524996

    Open questions at the time
    • Reframes but does not re-test every prior immune-complex-based catalytic claim
    • Role of ATP occupancy in the pseudo-active site functionally defined only later
  12. 2012 Medium

    ILK was linked to mTORC2 and ADAM12L, connecting the scaffold to TGF-beta-driven EMT and integrin-coupled survival signaling.

    Evidence Co-IP, siRNA, ILK inhibitor, Rictor Thr1135 phospho and Akt Ser473 readouts, Snail/Slug localization

    PMID:22310280 PMID:22767580

    Open questions at the time
    • Whether ILK directly phosphorylates Rictor conflicts with pseudokinase status
    • Immune-complex kinase activity attributed to ADAM12L not mechanistically defined
  13. 2013 High

    Conditional deletion established that beta1-integrin/ILK orients microtubule plus-ends and Golgi to drive apical clearance and epithelial lumen formation, independent of Rac1.

    Evidence Cre-lox deletion in mammary organoids, live microtubule imaging, endocytosis and Golgi-positioning assays

    PMID:23263281

    Open questions at the time
    • Molecular bridge from ILK to microtubule plus-ends in this context not identified
    • Effector linking ILK to endocytic apical clearance unresolved
  14. 2015 High

    The ELMO2-RhoG-ILK complex was shown to regulate microtubule dynamics integrin-independently in keratinocytes, defining a downstream Rac1/stathmin/GSK-3beta/CRMP2 pathway.

    Evidence Conditional ILK inactivation, live microtubule dynamics, ELMO2/RhoG rescue, Rac1/stathmin/GSK-3beta inhibitor experiments

    PMID:25995380

    Open questions at the time
    • How ILK acts on microtubules independent of integrin engagement not structurally defined
    • Direct versus indirect link to stathmin/CRMP2 unresolved
  15. 2018 High

    Structural and biochemical work defined the architecture of IPP-mediated F-actin bundling, mapped the kindlin-2 binding surface, and revealed ILK control of VEGFR3-beta1 integrin crosstalk in lymphatics.

    Evidence Structural analysis with F-actin bundling and WH2/ATP-site mutagenesis; conservation-guided kindlin-2 binding mutants; endothelial ILK/Itgb1 conditional deletion with VEGFR3 Co-IP and rescue

    PMID:30254023 PMID:30367047 PMID:30518533

    Open questions at the time
    • How Mg-ATP allosterically sensitizes bundling at the molecular level only partly defined
    • Mechanical regulation of ILK-beta1 assembly not structurally characterized
  16. 2019 Medium

    Arrhythmogenic cardiomyopathy variants in the ILK ankyrin repeat domain were linked to disease via IPP-complex disruption and cardiac dysfunction in vivo.

    Evidence Exome sequencing, in silico binding modeling, H9c2 localization, zebrafish cardiac-specific overexpression

    PMID:30802431

    Open questions at the time
    • ILK-PINCH disruption inferred from in silico modeling, not direct structural data
    • Zebrafish overexpression may not fully model human loss-of-function pathology
  17. 2021 Medium

    ILK was placed within a beta-arrestin1/betaPIX/Rac3 axis driving invadopodia and ECM proteolysis downstream of endothelin A receptor in ovarian cancer.

    Evidence Co-IP of ILK/betaPIX/beta-arrestin1, Rac3 activity, invadopodia and ECM degradation assays, in vivo ETAR antagonist

    PMID:33657382

    Open questions at the time
    • Direct ILK interaction surfaces in this complex not mapped
    • Requirement for the canonical IPP complex in this signaling not tested
  18. 2023 Medium

    ILK was shown to act non-cell-autonomously, exported in extracellular vesicles to activate fibroblasts via p38 MAPK and drive peritoneal fibrosis.

    Evidence EV proteomics, scRNA-seq, EV transfer, Rab27a knockdown and GW4869 inhibition, p38 MAPK readout

    PMID:37357686

    Open questions at the time
    • Molecular mechanism by which EV-delivered ILK activates p38 unclear
    • Whether ILK acts as scaffold or via partners in recipient cells not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the Mg-ATP-occupied pseudo-active site allosterically couples to F-actin bundling and partner engagement, and how mechanical force reconfigures ILK-integrin assemblies, remain mechanistically incomplete.
  • No full structural model of the force-dependent ILK-integrin-VEGFR3 switch
  • Allosteric transmission from ATP site to WH2-driven bundling not resolved at atomic resolution

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0008092 cytoskeletal protein binding 2 GO:0140657 ATP-dependent activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1474244 Extracellular matrix organization 3
Partners
ELMO2FERMT2ILKAPPARVINPINCHPXNRHOGRICTOR
Complex memberships
ELMO2-RhoG-ILK (ERI) complexILK-Rictor (mTORC2)IPP (ILK-PINCH-Parvin) complexfocal adhesion

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 ILK gene was mapped to human chromosome 11p15.5-p15.4 by fluorescence in situ hybridization, establishing its genomic locus. Fluorescence in situ hybridization (FISH) on metaphase and decondensed chromatin fibers Genomics Medium 9177792
2001 ILK binds directly to the paxillin LD1 motif via a paxillin-binding subdomain (PBS) in its C-terminus; PBS mutations abolish paxillin binding in vitro and prevent ILK localization to focal adhesions in fibroblasts, demonstrating that paxillin binding is required for focal adhesion targeting of ILK. Microsequencing of paxillin-binding proteins, in vitro binding assay, co-immunoprecipitation from fibroblasts, GFP-ILK immunofluorescence, PBS point mutant analysis The Journal of biological chemistry High 11304546
2002 C. elegans PAT-4/ILK (the sole ILK ortholog) functions as an adaptor protein within integrin adhesion complexes; kinase-dead ILK fully rescues pat-4 null mutants; UNC-112 was identified as a new ILK binding partner. In pat-4 null embryos, vinculin, UNC-89, actin and myosin fail to be recruited to integrin foci, while PAT-4/ILK itself requires UNC-52, integrin, and UNC-112 for proper recruitment. C. elegans genetic screen, null mutant analysis, transgenic kinase-dead rescue, yeast two-hybrid/binding assay for UNC-112 interaction Current biology : CB High 12015115
2002 PINCH-2 forms a complex with ILK via its LIM1 domain; PINCH-2–ILK and PINCH-1–ILK interactions are mutually exclusive; deletion of LIM1 prevents ILK binding and focal adhesion localization of PINCH-2; overexpression of PINCH-2 inhibits PINCH-1–ILK interaction and reduces cell spreading and migration. Co-immunoprecipitation, deletion mutant analysis, immunofluorescence, cell spreading/migration assays The Journal of biological chemistry Medium 12167643
2003 ILK-deficient mouse embryos die at peri-implantation due to failure to polarize epiblast and cavitate; ILK-null fibroblasts show abnormal F-actin aggregates, impaired spreading, delayed focal adhesion formation. Expression of kinase-inactive or paxillin-binding-defective ILK rescues actin organization, cell spreading, FA formation and proliferation, demonstrating that ILK modulates actin rearrangements at integrin-adhesion sites primarily through its adaptor function rather than kinase activity. Conditional mouse knockout (Cre/lox), fibroblast culture analysis, rescue with kinase-dead and paxillin-binding mutants, F-actin staining Genes & development High 12670870
2003 PINCH-1 and ILK are mutually required for cell spreading, motility, and survival in human cells; depletion of ILK by RNAi reduces Ser473 but not Thr308 phosphorylation of PKB/Akt. PINCH-1, ILK and alpha-parvin are mutually dependent for maintenance of their protein levels, coordinated by proteasomal degradation. RNA interference (siRNA) knockdown of PINCH-1, ILK, alpha-parvin; cell spreading/motility/survival assays; Western blot for PKB/Akt phosphorylation; proteasome inhibitor experiments The Journal of biological chemistry High 14551191
2004 ILKAP (protein phosphatase 2C) selectively associates with ILK, suppresses ILK immune complex kinase activity, and specifically inhibits GSK-3beta phosphorylation at S9 without affecting PKB Ser473 phosphorylation; overexpression of ILK but not dominant-negative ILK rescues ILKAP-mediated inhibition of GSK-3beta phosphorylation. siRNA silencing of ILKAP, ILK immune complex kinase assay, co-immunoprecipitation, overexpression rescue experiments Oncogene Medium 14990992
2004 ILK is required for assembly of fibrillar (matrix-forming) adhesions rich in alpha5beta1 integrin in endothelial cells; ILK depletion by RNAi eliminates fibrillar adhesions, impairs cell spreading/migration, and prevents capillary morphogenesis on Matrigel. RNA interference in bovine aortic endothelial cells, immunofluorescence for adhesion markers, migration assay, capillary morphogenesis assay Journal of cell science Medium 15316070
2004 ILK stimulates HIF-1alpha protein expression in a PKB/Akt- and mTOR/FRAP-dependent manner, leading to upregulation of VEGF in prostate cancer cells; in endothelial cells, VEGF stimulates ILK activity, and ILK inhibition blocks VEGF-mediated migration, capillary formation, and angiogenesis in vitro and in vivo. siRNA knockdown of ILK, ILK kinase inhibitor treatment, in vitro capillary formation assay, in vivo angiogenesis assay, Western blot for HIF-1alpha/VEGF Cancer cell Medium 14749128
2005 Overexpression of ILK induces actin filament rearrangements, lamellipodia formation, and increased cell migration/invasion via PI3K-dependent activation of Akt and Rac1; dominant-negative ILK abolishes fibronectin peptide (PHSRN)-induced actin rearrangements and migration. ILK overexpression and dominant-negative mutant expression, Rac1 activity assay, PI3K inhibitor treatment, migration/invasion assays Oncogene Medium 15735674
2006 Gi-coupled receptor agonists preferentially activate PI3K and ILK, leading to ILK-dependent phosphorylation of CPI-17 at Thr38 and MLC20 at Ser19, causing smooth muscle contraction; a kinase-inactive ILK mutant (R211A) abolishes these phosphorylations; ILK and the PAK1/p38 MAPK pathway reciprocally inhibit each other downstream of PI3K. Expression of ILK(R211A) dominant-negative mutant, siRNA for ILK, kinase activity assay, smooth muscle contraction measurement, phosphorylation assays The Biochemical journal Medium 16472257
2007 ILK is enriched in axonal tips of polarized neurons; inhibition of ILK (by inhibitors, kinase-inactive mutant, or siRNA) blocks axon formation, while kinase-hyperactive ILK induces multiple axons. Epistasis experiments place ILK downstream of PI3K and upstream of Akt and GSK-3beta in neuronal polarity. Chemical inhibitors of ILK, dominant-negative and hyperactive ILK mutants, siRNA knockdown, epistasis with PI3K/Akt/GSK-3beta pathway components, immunofluorescence Developmental biology Medium 17490631
2008 Rsu-1 co-localizes with ILK at focal contacts and co-immunoprecipitates with the ILK-PINCH1 complex in non-transformed cells; following Ras transformation, Rsu-1 association with the PINCH1-ILK complex is greatly reduced via a Mek-ERK-dependent mechanism involving Rsu-1 alternative splicing. Co-immunoprecipitation, immunofluorescence co-localization, MEK inhibitor treatment, siRNA knockdown, migration assay European journal of cell biology Medium 18436335
2009 ELMO2 simultaneously binds ILK and RhoG forming tripartite ERI complexes; Tbeta4 binds ILK in lamellipodia upon profilin-dependent release from G-actin, and Tbeta4-ILK complexes recruit and activate Akt2, resulting in matrix metalloproteinase-2 production; this couples actin polymerization at the leading edge to matrix degradation. FRET analysis of Tbeta4-G-actin interaction, Co-immunoprecipitation, spatial localization studies, Akt2 activation assay, MMP-2 production measurement Developmental cell Medium 19460343
2011 Recombinant ILK from bacteria or mammalian cells shows no kinase activity toward GSK-3beta with either Mn2+ or Mg2+; whole-cell kinase assay using mammalian lysates identified no specific ILK substrates; high-resolution crystal structure shows Mn-bound ILK adopts the same pseudo-active site conformation as Mg-bound ILK; the K220M 'kinase-dead' mutation impairs structural integrity rather than ATP binding, providing mechanistic basis for renal agenesis phenotype. ILK is a bona fide pseudokinase. In vitro kinase assay (recombinant protein), proteomics-based whole-cell kinase substrate screen, X-ray crystallography, thermodynamic stability analysis, mutagenesis The Journal of biological chemistry High 21524996
2012 ILK interacts with Rictor (mTORC2 component); TGF-β1 treatment induces ILK-Rictor complex formation and ILK-dependent phosphorylation of Rictor on Thr1135; disruption of the ILK/Rictor complex by siRNA suppresses TGF-β1-induced EMT and Snail/Slug nuclear translocation in mammary epithelial cells. Co-immunoprecipitation, siRNA knockdown, ILK inhibitor treatment, immunofluorescence for Snail/Slug localization, Western blot for Rictor phosphorylation Oncogene Medium 22310280
2012 ADAM12L co-immunoprecipitates with ILK in cells via its cytoplasmic tail; ADAM12L redistributes to focal adhesions with ILK upon beta1 integrin activation; depletion of ILK inhibits ADAM12L-induced Akt Ser473 phosphorylation and survival; overexpression of ADAM12L promotes kinase activity from ILK immunoprecipitates. Co-immunoprecipitation, immunofluorescence, ILK knockdown, ILK immune complex kinase assay, Akt phosphorylation Western blot Molecular biology of the cell Medium 22767580
2013 β1 integrins, via ILK, orient microtubule plus ends at the basolateral membrane; ILK depletion (Cre-lox deletion) prevents lumen formation in mammary gland organoids by blocking endocytic removal of apical proteins from the basement-membrane-cell interface and internal Golgi positioning; Rac1 is not involved in this axis. Cre-lox conditional deletion in mammary gland, 3D primary culture model, live microtubule dynamics imaging, endocytosis assays, Golgi positioning analysis Nature cell biology High 23263281
2015 ELMO2-RhoG-ILK (ERI) tripartite complexes regulate microtubule dynamics in an integrin-independent manner in differentiated keratinocytes; depletion of ILK reduces microtubule growth and increases catastrophe frequency; ERI-mediated microtubule stabilization requires ILK for ELMO2 or RhoG to have effect, and is mediated downstream through Rac1 activation of stathmin phosphorylation and CRMP2 activation via GSK-3beta. ILK conditional gene inactivation (Cre/lox), live microtubule dynamics analysis, ELMO2/RhoG overexpression rescue assays, Rac1/stathmin/GSK-3beta inhibitor experiments Molecular biology of the cell High 25995380
2018 Pseudokinase ILK recruits PINCH and Parvin into a heterotrimeric IPP complex that triggers F-actin filament bundling via two WASP-Homology-2 actin-binding motifs (one from PINCH, one from Parvin); Mg-ATP bound to the pseudoactive site of ILK sensitizes this process; mutations impairing ATP binding severely impair stress fiber formation, cell spreading and migration. Structural analysis, biochemical F-actin bundling assay, mutagenesis of WH2 motifs and ATP-binding site, cell spreading/migration assays, co-immunoprecipitation Nature communications High 30367047
2018 Kindlin-2 binds directly to a conserved surface on the C-lobe of the ILK pseudokinase domain (pKD); ILK mutations at this site inhibit kindlin-2 binding while maintaining pKD structural integrity; kindlin-binding-defective ILK mutants show impaired focal adhesion localization and fail to rescue spreading defects in ILK knockdown cells; kindlin-2 mutants with impaired ILK binding also fail to support cell spreading. Conservation-guided mutagenesis, binding assays, ILK knockdown rescue experiments, focal adhesion localization by immunofluorescence, cell spreading assays Journal of cell science High 30254023
2018 Endothelial cell-specific ILK depletion hyper-activates VEGFR3 signaling and causes lymphatic vascular overgrowth; ILK impedes interactions between VEGFR3 and β1 integrin; deletion of one Itgb1 allele rescues lymphatic overgrowth caused by ILK loss; mechanical stimulation disrupts ILK-β1 integrin assembly, enabling β1 integrin to interact with VEGFR3. Endothelial cell-specific Cre deletion of ILK and Itgb1, VEGFR3 phosphorylation assays, Co-immunoprecipitation of VEGFR3 and β1 integrin, lymphatic vessel growth quantification in cornea/skin/myocardium The EMBO journal High 30518533
2019 Two arrhythmogenic cardiomyopathy-associated missense variants (p.H33N and p.H77Y) in the ILK ankyrin repeat domain disrupt the ILK-PINCH complex (predicted by in silico binding studies); mutant ILK expressed in H9c2 cells shows aberrant prominent cytoplasmic localization; expression of p.H77Y and p.P70L ILK under a cardiac-specific promoter in zebrafish causes cardiac dysfunction and death by 2–3 weeks. Exome sequencing, in silico binding modeling, transfection in H9c2 cells with immunofluorescence, zebrafish cardiac-specific overexpression with functional cardiac assessment Translational research : the journal of laboratory and clinical medicine Medium 30802431
2021 Endothelin A receptor (ETAR) signaling drives invadopodia in ovarian cancer cells via β-arrestin1 linking ILK to the βPIX complex, which activates Rac3 GTPase; downstream, Rac3 phosphorylates PAK1 and cofilin to promote invadopodium-dependent ECM proteolysis and invasion; ILK/Rac3 signaling also supports cancer-mesothelial cell communication and transmigration. Co-immunoprecipitation of ILK/βPIX/β-arrestin1, Rac3 activity assay, invadopodium formation and ECM degradation assays, in vivo ETAR antagonist treatment Cell reports Medium 33657382
2023 Injured mesothelial cells produce extracellular vesicles containing high levels of ILK; ILK packaged in EVs is delivered to fibroblasts and activates them via the p38 MAPK signaling pathway, driving peritoneal fibrogenesis. EV proteomics, single-cell RNA sequencing, EV isolation and transfer experiments, Rab27a knockdown to block EV secretion, Western blot for p38 MAPK activation in recipient fibroblasts, GW4869 (EV inhibitor) treatment Journal of extracellular vesicles Medium 37357686

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 ILK, PINCH and parvin: the tIPP of integrin signalling. Nature reviews. Molecular cell biology 571 16493410
2005 Integrin-linked kinase: a cancer therapeutic target unique among its ILK. Nature reviews. Cancer 509 15630415
2001 Integrin-linked kinase (ILK) and its interactors: a new paradigm for the coupling of extracellular matrix to actin cytoskeleton and signaling complexes. The Journal of cell biology 387 11696562
2003 Integrin-linked kinase (ILK) is required for polarizing the epiblast, cell adhesion, and controlling actin accumulation. Genes & development 321 12670870
2002 C. elegans PAT-4/ILK functions as an adaptor protein within integrin adhesion complexes. Current biology : CB 261 12015115
2004 Regulation of tumor angiogenesis by integrin-linked kinase (ILK). Cancer cell 235 14749128
1999 Integrin-linked kinase (ILK): a regulator of integrin and growth-factor signalling. Trends in cell biology 213 10407411
2009 The ILK/PINCH/parvin complex: the kinase is dead, long live the pseudokinase! The EMBO journal 209 20033063
2001 Inhibition of integrin linked kinase (ILK) suppresses beta-catenin-Lef/Tcf-dependent transcription and expression of the E-cadherin repressor, snail, in APC-/- human colon carcinoma cells. Oncogene 209 11244511
2000 The integrin-linked kinase (ILK) suppresses anoikis. Oncogene 205 10949937
2000 Cell-substrate interactions and signaling through ILK. Current opinion in cell biology 189 10712922
2013 An integrin-ILK-microtubule network orients cell polarity and lumen formation in glandular epithelium. Nature cell biology 185 23263281
2001 Integrin-linked kinase (ILK) binding to paxillin LD1 motif regulates ILK localization to focal adhesions. The Journal of biological chemistry 183 11304546
2003 PINCH-1 is an obligate partner of integrin-linked kinase (ILK) functioning in cell shape modulation, motility, and survival. The Journal of biological chemistry 180 14551191
2003 The role of integrin-linked kinase (ILK) in cancer progression. Cancer metastasis reviews 154 12884912
2005 ILK mediates actin filament rearrangements and cell migration and invasion through PI3K/Akt/Rac1 signaling. Oncogene 127 15735674
2003 alpha(v) integrins regulate cell proliferation through integrin-linked kinase (ILK) in ovarian cancer cells. Oncogene 126 12642872
2004 The PINCH-ILK-parvin complexes: assembly, functions and regulation. Biochimica et biophysica acta 123 15246679
2012 Role of the integrin-linked kinase (ILK)/Rictor complex in TGFβ-1-induced epithelial-mesenchymal transition (EMT). Oncogene 118 22310280
2007 Targeting SPARC expression decreases glioma cellular survival and invasion associated with reduced activities of FAK and ILK kinases. Oncogene 117 17213807
2016 Tissue Stiffness and Hypoxia Modulate the Integrin-Linked Kinase ILK to Control Breast Cancer Stem-like Cells. Cancer research 115 27503933
2008 Alphavbeta3 and alphavbeta5 integrins control glioma cell response to ionising radiation through ILK and RhoB. International journal of cancer 114 18464290
2012 ILK: a pseudokinase in the center stage of cell-matrix adhesion and signaling. Current opinion in cell biology 105 22763012
2002 Characterization of PINCH-2, a new focal adhesion protein that regulates the PINCH-1-ILK interaction, cell spreading, and migration. The Journal of biological chemistry 95 12167643
2000 Integrin-linked kinase (ILK): a "hot" therapeutic target. Biochemical pharmacology 88 11007949
2005 PINCH, N(i)ck and the ILK: network wiring at cell-matrix adhesions. Trends in cell biology 87 16084094
2022 Integrin-linked kinase (ILK): the known vs. the unknown and perspectives. Cellular and molecular life sciences : CMLS 81 35089438
2010 Hypoxia induces BMP-2 expression via ILK, Akt, mTOR, and HIF-1 pathways in osteoblasts. Journal of cellular physiology 78 20232298
2016 ILK-PI3K/AKT pathway participates in cutaneous wound contraction by regulating fibroblast migration and differentiation to myofibroblast. Laboratory investigation; a journal of technical methods and pathology 76 27111285
2019 Significance of integrin-linked kinase (ILK) in tumorigenesis and its potential implication as a biomarker and therapeutic target for human cancer. American journal of cancer research 75 30755822
2018 ILK Expression in Colorectal Cancer Is Associated with EMT, Cancer Stem Cell Markers and Chemoresistance. Cancer genomics & proteomics 74 29496692
2001 Dysregulation of integrin-linked kinase (ILK) signaling in colonic polyposis. Oncogene 71 11593435
2008 The Rsu-1-PINCH1-ILK complex is regulated by Ras activation in tumor cells. European journal of cell biology 69 18436335
2004 ILKAP regulates ILK signaling and inhibits anchorage-independent growth. Oncogene 69 14990992
2002 Regulation of fibronectin matrix deposition and cell proliferation by the PINCH-ILK-CH-ILKBP complex. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 69 12060675
2004 ILK is required for the assembly of matrix-forming adhesions and capillary morphogenesis in endothelial cells. Journal of cell science 67 15316070
2020 β1 integrin, ILK and mTOR regulate collagen synthesis in mechanically loaded tendon cells. Scientific reports 62 32724089
2011 Biochemical, proteomic, structural, and thermodynamic characterizations of integrin-linked kinase (ILK): cross-validation of the pseudokinase. The Journal of biological chemistry 61 21524996
2013 ILK: a pseudokinase with a unique function in the integrin-actin linkage. Biochemical Society transactions 60 23863169
1998 ILK (beta1-integrin-linked protein kinase): a novel immunohistochemical marker for Ewing's sarcoma and primitive neuroectodermal tumour. Virchows Archiv : an international journal of pathology 58 9737788
2009 Spatial coordination of actin polymerization and ILK-Akt2 activity during endothelial cell migration. Developmental cell 57 19460343
2006 Gi-coupled receptors mediate phosphorylation of CPI-17 and MLC20 via preferential activation of the PI3K/ILK pathway. The Biochemical journal 57 16472257
2008 Suppression of VEGF secretion and changes in glioblastoma multiforme microenvironment by inhibition of integrin-linked kinase (ILK). Molecular cancer therapeutics 56 18202010
2013 The differential expression of TGF-β1, ILK and wnt signaling inducing epithelial to mesenchymal transition in human renal fibrogenesis: an immunohistochemical study. International journal of clinical and experimental pathology 55 24040439
2011 Cten signals through integrin-linked kinase (ILK) and may promote metastasis in colorectal cancer. Oncogene 54 21339732
2018 Non-catalytic signaling by pseudokinase ILK for regulating cell adhesion. Nature communications 51 30367047
2017 The ILK-MMP9-MRTF axis is crucial for EndMT differentiation of endothelial cells in a tumor microenvironment. Biochimica et biophysica acta. Molecular cell research 46 28893556
2014 Involvement of ILK/ERK1/2 and ILK/p38 pathways in mediating the enhanced osteoblast differentiation by micro/nanotopography. Acta biomaterialia 46 24769109
2012 Induction of membrane circular dorsal ruffles requires co-signalling of integrin-ILK-complex and EGF receptor. Journal of cell science 46 22357970
2010 ILK mediates LPS-induced vascular adhesion receptor expression and subsequent leucocyte trans-endothelial migration. Cardiovascular research 46 20164118
2010 Suppression of Her2/neu expression through ILK inhibition is regulated by a pathway involving TWIST and YB-1. Oncogene 45 20838384
2007 Role of the integrin-linked kinase (ILK) in determining neuronal polarity. Developmental biology 45 17490631
2018 Identification of ILK as a critical regulator of VEGFR3 signalling and lymphatic vascular growth. The EMBO journal 44 30518533
2019 Chronic kidney disease induced by an adenine rich diet upregulates integrin linked kinase (ILK) and its depletion prevents the disease progression. Biochimica et biophysica acta. Molecular basis of disease 42 30726718
2013 Activated PAR-2 regulates pancreatic cancer progression through ILK/HIF-α-induced TGF-α expression and MEK/VEGF-A-mediated angiogenesis. The American journal of pathology 42 23764046
2019 Mutations in ILK, encoding integrin-linked kinase, are associated with arrhythmogenic cardiomyopathy. Translational research : the journal of laboratory and clinical medicine 39 30802431
2018 Integrin-linked kinase (ILK) and src homology 2 domain-containing phosphatase 2 (SHP2): Novel targets in EGFR-mutation positive non-small cell lung cancer (NSCLC). EBioMedicine 38 30473379
1997 Mapping of the gene encoding the integrin-linked kinase, ILK, to human chromosome 11p15.5-p15.4. Genomics 37 9177792
2010 ILK expression in human basal cell carcinoma correlates with epithelial-mesenchymal transition markers and tumour invasion. Histopathology 36 20546345
2009 How ILK and kindlins cooperate to orchestrate integrin signaling. Current opinion in cell biology 35 19560331
2019 Sparc, an EPS-induced gene, modulates the extracellular matrix and mitochondrial function via ILK/AMPK pathways in C2C12 cells. Life sciences 34 31150687
2013 Small interfering RNA targeting ILK inhibits metastasis in human tongue cancer cells through repression of epithelial-to-mesenchymal transition. Experimental cell research 34 23707970
2021 POSTN promotes proliferation and epithelial-mesenchymal transition in renal cell carcinoma through ILK/AKT/mTOR pathway. Journal of Cancer 33 34093819
2020 Monocyte Chemoattractant Protein 1 Promotes VEGF-A Expression in OSCC by Activating ILK and MEK1/2 Signaling and Downregulating miR-29c. Frontiers in oncology 31 33330077
2023 Extracellular vesicle-packaged ILK from mesothelial cells promotes fibroblast activation in peritoneal fibrosis. Journal of extracellular vesicles 30 37357686
2022 New Perspectives on the Role of Integrin-Linked Kinase (ILK) Signaling in Cancer Metastasis. Cancers 30 35804980
2015 PARVA promotes metastasis by modulating ILK signalling pathway in lung adenocarcinoma. PloS one 30 25738875
2014 Thymosin β4 induces invasion and migration of human colorectal cancer cells through the ILK/AKT/β-catenin signaling pathway. Biochemical and biophysical research communications 30 25218472
2009 Integrin linked kinase (ILK) expression and function in vascular smooth muscle cells. Cell adhesion & migration 30 19262169
2012 Targeting ILK and β4 integrin abrogates the invasive potential of ovarian cancer. Biochemical and biophysical research communications 29 23026047
2011 How integrins control mammary epithelial differentiation: a possible role for the ILK-PINCH-Parvin complex. FEBS letters 28 21570968
2023 Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway. Zoological research 27 36866625
2020 The focal adhesion protein Integrin-Linked Kinase (ILK) as an important player in breast cancer pathogenesis. Cell adhesion & migration 26 33043811
2018 Kindlin-2 interacts with a highly conserved surface of ILK to regulate focal adhesion localization and cell spreading. Journal of cell science 26 30254023
2015 An ELMO2-RhoG-ILK network modulates microtubule dynamics. Molecular biology of the cell 26 25995380
2017 Peripheral insulin resistance in ILK-depleted mice by reduction of GLUT4 expression. The Journal of endocrinology 25 28490443
2016 Involvement of Tiam1, RhoG and ELMO2/ILK in Rac1-mediated phagocytosis in human trabecular meshwork cells. Experimental cell research 25 27539661
2021 Astragalus Polysaccharide Reduces Blood Pressure, Renal Damage, and Dysfunction Through the TGF-β1-ILK Pathway. Frontiers in pharmacology 24 34690754
2012 ILK induces cardiomyogenesis in the human heart. PloS one 24 22666394
2008 ILK overexpression in human hepatocellular carcinoma and liver cirrhosis correlates with activation of Akt. Oncology reports 24 19020711
2021 Endothelin-1 drives invadopodia and interaction with mesothelial cells through ILK. Cell reports 23 33657382
2013 ILK modulates epithelial polarity and matrix formation in hair follicles. Molecular biology of the cell 23 24371086
2017 ILK regulates MSCs survival and angiogenesis partially through AKT and mTOR signaling pathways. Acta histochemica 22 28457660
2012 Identification of ILK as a new partner of the ADAM12 disintegrin and metalloprotease in cell adhesion and survival. Molecular biology of the cell 22 22767580
2007 Role of ERK1/2 and PI3-K in the regulation of CTGF-induced ILK expression in HK-2 cells. Clinica chimica acta; international journal of clinical chemistry 22 17498677
2022 Partitioning defective 6 homolog alpha (PARD6A) promotes epithelial-mesenchymal transition via integrin β1-ILK-SNAIL1 pathway in ovarian cancer. Cell death & disease 21 35379775
2023 The Expression of TGF-β1, SMAD3, ILK and miRNA-21 in the Ectopic and Eutopic Endometrium of Women with Endometriosis. International journal of molecular sciences 20 36768775
2021 β-elemene alleviates airway stenosis via the ILK/Akt pathway modulated by MIR143HG sponging miR-1275. Cellular & molecular biology letters 19 34118875
2019 ILK promotes survival and self-renewal of hypoxic MSCs via the activation of lncTCF7-Wnt pathway induced by IL-6/STAT3 signaling. Gene therapy 19 30814673
2018 ILK-induced epithelial-mesenchymal transition promotes the invasive phenotype in adenomyosis. Biochemical and biophysical research communications 19 29409901
2014 Integrin linked kinase (ILK) is required for lens epithelial cell survival, proliferation and differentiation. Experimental eye research 19 24472646
2014 Gender-based differences in cardiac remodeling and ILK expression after myocardial infarction. Arquivos brasileiros de cardiologia 19 25098374
2020 Downstream Effectors of ILK in Cisplatin-Resistant Ovarian Cancer. Cancers 18 32260415
2018 ILK enhances migration and invasion abilities of human endometrial stromal cells by facilitating the epithelial-mesenchymal transition. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 18 30182767
2019 MicroR-542-3p can mediate ILK and further inhibit cell proliferation, migration and invasion in osteosarcoma cells. Aging 17 30636169
2012 Integrin-linked kinase (ILK) expression correlates with tumor severity in clear cell renal carcinoma. Pathology oncology research : POR 17 22814720
2010 Integrin-linked kinase (ILK) in pulmonary fibrosis. Virchows Archiv : an international journal of pathology 17 20857141
2009 Oncogenic ILK, tumor suppression and all that JNK. Cell cycle (Georgetown, Tex.) 17 19923885
2021 Targeting the ILK/YAP axis by LFG-500 blocks epithelial-mesenchymal transition and metastasis. Acta pharmacologica Sinica 16 33879841
2017 HMGA1 participates in MHCC97H cell proliferation and invasion through the ILK/Akt/GSK3β signaling pathway. Molecular medicine reports 16 29152644

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