Affinage

PTK7

Inactive tyrosine-protein kinase 7 · UniProt Q13308

Length
1070 aa
Mass
118.4 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTK7 is a catalytically inactive transmembrane receptor that functions as a polarity co-receptor governing planar cell polarity (PCP) and convergent extension during vertebrate morphogenesis (PMID:15229603, PMID:19439496). Although its sequence places it among receptor tyrosine kinases, the kinase domain carries non-canonical motif residues and the protein neither autophosphorylates nor alters cellular phosphotyrosine, defining it as a pseudokinase/defective RTK (PMID:8882711, PMID:15019986). At the plasma membrane PTK7 organizes non-canonical Wnt signaling by recruiting Dishevelled together with Frizzled7, a function that requires the Dsh PDZ domain and the PTK7 kinase domain and is facilitated by RACK1 acting through PKCδ1 (PMID:19004858, PMID:21350015). PTK7 partners with the Wnt5a co-receptor ROR2 to drive JNK activation and morphogenetic cell movements, the latter depending on ROR2 catalytic activity (PMID:26499793, PMID:26680417). It simultaneously restrains canonical Wnt/β-catenin signaling by binding Wnt ligands and acting at the level of Frizzled, and by physically stabilizing LRP6, thereby reciprocally tuning the canonical and PCP branches; canonical Wnt in turn drives Fzd7-dependent caveolar endocytosis and lysosomal degradation of PTK7 (PMID:21772251, PMID:24353057, PMID:28420671). Downstream, PTK7 sustains junctional contractility through a PTK7–Src–ROCK2 module and controls myosin II activity in supporting cells to orient hair cell polarity (PMID:24703874, PMID:22560610). PTK7 is processed by sequential cleavage: MT1-MMP and ADAM17 shed the ectodomain to release a soluble fragment, after which γ-secretase liberates an intracellular C-terminal fragment that translocates to the nucleus and promotes proliferation and migration (PMID:20837484, PMID:22665490). The shed extracellular domain is itself the key signaling unit, sufficient to rescue both PCP and β-catenin defects and acting in trans as a ligand-like modulator of VEGFR2/KDR, the adhesion GPCR GPR133, and non-canonical Wnt/Ca2+–YAP signaling (PMID:23533179, PMID:25986862, PMID:37354459, PMID:36631445). In disease, PTK7 functions as an oncogenic co-receptor that potentiates FGFR1 and EGFR signaling and promotes invasion and EMT (PMID:31490704, PMID:37569547, PMID:35977930), and loss-of-function or interaction-altering variants cause scoliosis and neural tube defects in zebrafish, mouse, and human cohorts (PMID:25182715, PMID:20704721, PMID:30689296).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 Medium

    Established the molecular identity of PTK7 as an RTK-like receptor with anomalous catalytic-motif residues, raising the question of whether it functions as an active kinase.

    Evidence Full-length cDNA cloning and sequence/expression analysis of human PTK7

    PMID:8882711

    Open questions at the time
    • Did not test catalytic activity directly
    • No functional or pathway assignment
  2. 2004 High

    Resolved the catalytic question by showing PTK7 is a pseudokinase, and independently placed it genetically in the vertebrate PCP pathway, defining its core developmental role.

    Evidence In vitro kinase/phosphotyrosine assays in COS-1 cells; mouse knockout, Xenopus knockdown, and Ptk7×Vangl2 epistasis with hair cell imaging

    PMID:15019986 PMID:15229603

    Open questions at the time
    • Did not identify the molecular partners transducing PCP signal
    • Mechanism of polarity readout unknown
  3. 2008 High

    Defined the proximal molecular mechanism: PTK7 recruits Dishevelled to the membrane with Frizzled7, linking the receptor to non-canonical Wnt transduction.

    Evidence Xenopus explant assays, reciprocal Co-IP, domain-deletion constructs, neural crest transplantation

    PMID:19004858

    Open questions at the time
    • How the pseudokinase domain engages Dsh structurally unresolved
    • Did not address canonical Wnt branch
  4. 2009 High

    Established the cell-behavioral output of PTK7 loss — failure of mediolateral elongation, alignment, and convergent extension during gastrulation.

    Evidence High-resolution live imaging of Ptk7 mutant mouse embryos

    PMID:19439496

    Open questions at the time
    • Did not connect cell behavior to specific cytoskeletal effectors
    • Molecular link to PCP core proteins not shown
  5. 2010 High

    Identified MT1-MMP as the principal PTK7 sheddase and showed proteolysis is functionally required, introducing regulated cleavage as a control point.

    Evidence In vitro cleavage with site mapping (PKP621↓LI), uncleavable L622D mutant, MT1-MMP siRNA, zebrafish CE assay

    PMID:20837484

    Open questions at the time
    • Fate of cleavage fragments not yet defined
    • In vivo sheddase relevance in mammals not tested
  6. 2010 High

    Linked PTK7 to disease-relevant proteolysis and to context-specific roles, showing the chuzhoi mutation impairs membrane localization and that soluble ectodomain acts as a VEGF decoy and a survival factor in leukemia.

    Evidence ENU mutant positional cloning with PCP epistasis; recombinant sPTK7/HUVEC angiogenesis assays; PTK7 overexpression and PTK7-Fc decoy in AML cells

    PMID:18471990 PMID:20558616 PMID:20704721

    Open questions at the time
    • Mechanistic basis of decoy activity not yet defined (later resolved as KDR binding)
    • Intracellular-region effector in AML not identified
  7. 2011 High

    Expanded the membrane signaling module by adding RACK1/PKCδ1 as required for PTK7-mediated Dsh localization, and demonstrated PTK7 binds Wnt ligands to inhibit canonical Wnt at the Frizzled level.

    Evidence Xenopus Co-IP/morpholino/explant assays; Wnt ligand Co-IP, luciferase reporters, and epistasis in Xenopus and Drosophila; chz creates aberrant MT1-MMP site

    PMID:21350015 PMID:21518755 PMID:21772251

    Open questions at the time
    • How a single receptor switches between canonical inhibition and PCP activation not mechanistically unified
    • Structural basis of Wnt binding unknown
  8. 2012 High

    Connected PTK7 to mechanical polarity outputs and defined the full proteolytic cascade ending in a nuclear intracellular fragment.

    Evidence Mouse mosaic/double-mutant analysis with vinculin and myosin II readouts; ADAM17 knockdown and γ-secretase inhibition with nuclear fractionation and proliferation assays

    PMID:22560610 PMID:22665490 PMID:23095747

    Open questions at the time
    • Nuclear targets of PTK7-CTF2 not identified
    • Relationship between MT1-MMP and ADAM17 shedding pathways unresolved
  9. 2013 High

    Showed the extracellular domain alone is the functional unit for both Wnt branches and that PTK7 stabilizes LRP6 to reciprocally tune canonical and PCP signaling.

    Evidence ZFN MZptk7 zebrafish with ectodomain rescue and β-catenin readouts; Co-IP and Xenopus knockdown of PTK7/LRP6

    PMID:23533179 PMID:24353057

    Open questions at the time
    • How the membrane-tethered ectodomain signals without the cytoplasmic tail unexplained
    • LRP6 stabilization mechanism unknown
  10. 2014 High

    Defined a junctional PTK7–Src–ROCK2 contractility module and dissected differential signaling and motility roles of full-length versus cleaved PTK7.

    Evidence Co-IP and knockdown with active-Src/ROCK2 imaging plus in vivo SFK inhibition; transcriptomic/kinome profiling of PTK7 constructs; HT1080 metastasis models; Id1/TGF-β rescue in glioma

    PMID:24618420 PMID:24703874 PMID:25006253 PMID:25204555

    Open questions at the time
    • Direct substrate of Src in this module not defined
    • How cleavage state biases 2D vs 3D motility mechanistically unclear
  11. 2014 High

    Linked PTK7 dysfunction to scoliosis, establishing a developmental-disease axis through Wnt dysregulation.

    Evidence ZFN and MZ ptk7 zebrafish with microCT and functional testing of a human idiopathic-scoliosis variant

    PMID:25182715

    Open questions at the time
    • Tissue-specific requirement for spinal curvature not localized
    • Mechanism linking Wnt to spine geometry unresolved
  12. 2015 High

    Identified ROR2 as a Wnt5a co-receptor partner driving JNK and morphogenesis, and showed sPTK7 binds KDR/VEGFR2 with biphasic effects, mechanistically explaining the decoy activity.

    Evidence Co-IP, JNK assays, nuclear fractionation and papc reporters in mammalian cells/Xenopus; kinase-dead Ror2 rescue in neural crest; KDR binding and dose-dependent VEGF assays

    PMID:25986862 PMID:26499793 PMID:26680417

    Open questions at the time
    • Stoichiometric switch between activating and inhibitory sPTK7 not defined in vivo
    • Whether ROR2 phosphorylates PTK7 partners unknown
  13. 2017 Medium

    Revealed a feedback mechanism whereby canonical Wnt triggers Fzd7-dependent caveolar endocytosis and lysosomal degradation of PTK7, explaining mutual antagonism between PTK7 and canonical Wnt.

    Evidence Endocytosis/caveolin and lysosomal inhibition, Fzd7 loss-of-function, Wnt reporters in Xenopus

    PMID:28420671

    Open questions at the time
    • Single-lab trafficking study
    • Adaptor linking PTK7 to caveolar machinery not identified
  14. 2019 Medium

    Extended PTK7's co-receptor role to oncogenic RTK signaling, showing ligand-independent FGFR1 activation, and connected interaction-altering variants to neural tube defects.

    Evidence Co-IP, colocalization, knockdown with FGFR1 phosphorylation/functional assays in ESCC; Co-IP of NTD variants with Dvl2 and protein-stability assays

    PMID:30689296 PMID:31490704

    Open questions at the time
    • Mechanism of ligand-free FGFR1 activation not structurally defined
    • Causality of NTD variants beyond altered Dvl2 binding not established
  15. 2022 Medium

    Implicated PTK7 in Rho-GTPase–driven EMT/plasticity and in drug resistance via a stabilized NDRG1 axis, broadening its junctional adhesion roles in cancer.

    Evidence Phosphoproteomics and 3D imaging with cofetuzumab in ovarian cancer; BirA* proximity labeling and Co-IP with drug-sensitivity assays in NSCLC

    PMID:35977930 PMID:36205702

    Open questions at the time
    • Direct biochemical link between PTK7 and Rho-GTPase regulators not defined
    • PTK7–NDRG1 stabilization mechanism unknown
  16. 2023 High

    Identified new trans-acting roles for the PTK7 ectodomain as a positive allosteric modulator of the adhesion GPCR GPR133 and as a senescence-secreted activator of Wnt/Ca2+–YAP signaling, plus interactions with FGFR1/EGFR in TNBC.

    Evidence Affinity proteomics, Co-IP, domain-deletion signaling assays in glioblastoma; intestinal organoid/SASP fractionation with Ca2+ imaging and YAP/FZD7 epistasis; Co-IP and phospho-signaling in TNBC

    PMID:36631445 PMID:37354459 PMID:37569547

    Open questions at the time
    • Structural basis of GPR133 allosteric modulation undefined
    • Receptor mediating intracellular Ca2+ output beyond FZD7 not fully mapped
  17. 2024 High

    Provided structural definition of an aptamer-binding region within PTK7 Ig domains 3–4, establishing a high-resolution view of the ectodomain.

    Evidence Crystal structure of sgc8c–Ig(3-4) complex with MS footprinting, MD simulation, and mutagenesis

    PMID:38889444

    Open questions at the time
    • Structure of full-length receptor or ligand complexes not solved
    • Does not address signaling-competent conformations

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single pseudokinase ectodomain selects among its many co-receptor partners (Fzd7, ROR2, LRP6, KDR, FGFR1, EGFR, GPR133) to switch between canonical inhibition, PCP activation, and oncogenic RTK potentiation remains the central unresolved question.
  • No structural model of PTK7 in a signaling complex
  • Quantitative rules governing partner choice and cleavage-state output undefined
  • In vivo function of the nuclear intracellular fragment's targets unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 4 GO:0005886 plasma membrane 4 GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3
Partners
DVLFGFR1FZD7GPR133KDRLRP6ROR2SRC

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 PTK7 is required for planar cell polarity (PCP) in vertebrates: mouse PTK7 mutations disrupt neural tube closure and stereociliary bundle orientation, and PTK7 shows genetic interaction with the Vangl2 (Van Gogh homologue) mutation. PTK7 is dynamically localized during hair cell polarization. Xenopus PTK7 is required for neural convergent extension and neural tube closure. Mouse mutant analysis, Xenopus loss-of-function (morpholino), genetic epistasis (Ptk7 × Vangl2Lp double mutant), live imaging of hair cell polarization Nature High 15229603
2008 PTK7 recruits Dishevelled (Dsh) to the plasma membrane to regulate neural crest migration. This function depends on the PDZ domain of Dsh and the conserved kinase domain of PTK7. PTK7 is found in a complex with Dsh and Frizzled7 by immunoprecipitation, and endogenous PTK7 is required for Frizzled7-mediated Dsh membrane localization. A PTK7 deletion construct deficient in Dsh binding inhibits neural crest migration. Xenopus ectodermal explant assays, immunoprecipitation, morpholino knockdown, domain deletion constructs, transplantation of neural crest cells Development High 19004858
2009 PTK7 is essential for mediolateral cell elongation, alignment, polarized protrusive activity, and convergent extension (CE) during mouse gastrulation. In Ptk7 mutants, mesoderm cells fail to elongate and align upon leaving the primitive streak, and CE and axial elongation fail. Loss of PTK7 also unleashes cryptic radial intercalation, causing excessive mesodermal thinning. High-resolution time-lapse imaging of living mouse embryos, Ptk7 mutant mouse analysis Development High 19439496
2010 Membrane type-1 matrix metalloproteinase (MT1-MMP) acts as a principal sheddase of PTK7, directly cleaving the PKP(621)↓LI sequence in the seventh Ig-like domain to generate a soluble N-terminal PTK7 fragment (sPTK7). Expression of full-length membrane PTK7 in cancer cells reorganizes the actin cytoskeleton and inhibits cell invasion; MT1-MMP silencing and the uncleavable L622D PTK7 mutant confirm the biological significance of this proteolysis. In vitro cleavage assay, MT1-MMP siRNA silencing, uncleavable L622D mutant analysis, zebrafish convergent extension assay, actin cytoskeleton imaging The Journal of Biological Chemistry High 20837484
2011 RACK1 is a novel interaction partner of PTK7 required for neural tube closure. RACK1 facilitates PTK7-mediated membrane localization of Dishevelled (DSH) by recruiting PKCδ1. RACK1 is necessary for PTK7-DSH interaction and for neural convergent extension in Xenopus. Xenopus loss-of-function (morpholino), Co-IP, explant assays, dominant-negative constructs Development High 21350015
2011 PTK7/Otk co-precipitates canonical Wnt3a and Wnt8 ligands and inhibits canonical Wnt signaling. PTK7 loss-of-function activates canonical Wnt activity; epistasis places PTK7 at the level of the Frizzled receptor. In Drosophila, Otk interacts with Wnt4 and opposes canonical Wnt signaling in embryonic patterning. Co-immunoprecipitation, luciferase reporter assays (Xenopus, Drosophila), genetic epistasis, loss-of-function in multiple organisms The EMBO Journal High 21772251
2012 PTK7 regulates myosin II activity in supporting cells to orient planar cell polarity in the mammalian auditory epithelium. PTK7 and Frizzled3/Frizzled6 act in parallel with opposing effects on hair cell PCP. PTK7 is required in supporting cells (not hair cells) for hair cell PCP. In Ptk7 mutants, compromised myosin II activity results in loss of planar asymmetry of junctional vinculin, which is restored in Fz3−/−;Ptk7−/− double mutants. Mouse mosaic analysis, double mutant epistasis (Fz3−/−;Ptk7−/−), vinculin localization as tension readout, myosin II inhibition Current Biology High 22560610
2012 PTK7 undergoes sequential ectodomain shedding: ADAM17 cleaves full-length PTK7 to generate sPTK7-Ig1-7 (shed extracellular domain) and PTK7-CTF1; γ-secretase then cleaves PTK7-CTF1 to generate PTK7-CTF2. PTK7-CTF2 localizes to the nucleus and enhances cell proliferation, migration, and anchorage-independent colony formation in colon cancer cells. Protease inhibitor treatment, ADAM17 knockdown, γ-secretase inhibitors, immunoblotting, nuclear fractionation, proliferation/migration assays The Journal of Biological Chemistry High 22665490
2012 PTK7 ectodomain shedding in HT1080 fibrosarcoma cells involves both ADAM proteinase-mediated and MT1-MMP-mediated cleavage of the PTK7 ectodomain. γ-Secretase cleaves the resulting C-terminal PTK7 fragments; the γ-secretase product is predominantly degraded by the proteasome, but when the C-terminal fragment is overexpressed it enters the nucleus. Protease inhibitor experiments, overexpression of PTK7 C-terminal fragment, nuclear/cytoplasmic fractionation, immunoblotting The Journal of Biological Chemistry Medium 23095747
2013 PTK7 modulates LRP6 protein levels: PTK7 and LRP6 physically interact, and PTK7 depletion strongly reduces LRP6 protein levels. Because LRP6 positively modulates Wnt/β-catenin but negatively modulates Wnt/PCP, PTK7 stabilization of LRP6 reciprocally regulates both canonical and non-canonical Wnt activities. Co-immunoprecipitation, morpholino knockdown in Xenopus, immunoblotting, Wnt reporter assays, meis3 expression analysis Development Medium 24353057
2013 The extracellular domain of Ptk7 (plasma membrane-tethered fragment) is sufficient to rescue both PCP morphogenesis and Wnt/β-catenin patterning defects in maternal-zygotic ptk7 mutant zebrafish, indicating the extracellular domain acts as the key functional unit regulating both signaling branches. Zinc-finger nuclease gene targeting (MZptk7 mutant zebrafish), rescue with extracellular domain construct, β-catenin target gene expression analysis Development High 23533179
2014 PTK7 interacts with Src kinase and stimulates Src signaling along cell-cell contacts in epithelial cells. ROCK2 is a downstream target of junctional PTK7-Src signaling. PTK7 knockdown reduces active Src at cell-cell contacts, delocalizes ROCK2, decreases junctional contractility, and increases basal actomyosin. In vivo, Src family kinase (SFK) activity is critical for PCP in the auditory sensory epithelium and PTK7-SFK signaling regulates tyrosine phosphorylation of junctional ROCK2. Co-IP (PTK7-Src interaction), PTK7 knockdown in cultured epithelial cells, immunofluorescence of active Src/ROCK2, pharmacological SFK inhibition in mouse auditory epithelium, phosphotyrosine analysis of ROCK2 Developmental Cell High 24703874
2014 Full-length membrane PTK7 and its proteolytic fragments (N-terminal soluble ectodomain, C-terminal 622–1070 and 726–1070 fragments) differentially regulate migration-related genes. Full-length PTK7 activates Akt and c-Jun pathways and suppresses multiple migration genes; C-terminal fragments act via RAS-ERK and CREB/ATF1 pathways and upregulate cadherin-11. Genome-wide transcriptional arrays, kinome arrays, stable expression of PTK7 constructs in HT1080 cells, immunoblotting validation Cell Communication and Signaling Medium 24618420
2015 PTK7 associates with ROR2 to form a heterodimeric complex. PTK7 and ROR2 physically and functionally interact with Wnt5a, leading to JNK activation and cell movements. Wnt5a stimulates release of the tagged PTK7 intracellular domain, which translocates to the nucleus and activates papc expression. In Xenopus, Ptk7 functionally interacts with Ror2 to regulate papc expression and morphogenesis, and Ptk7 is required for Wnt5a-induced papc activation. Co-immunoprecipitation in mammalian cells, JNK activation assays, cell movement assays, Xenopus gain/loss-of-function, nuclear fractionation, papc reporter assays The Journal of Biological Chemistry High 26499793
2015 PTK7 interacts with ROR2 in Xenopus neural crest cells (Co-IP), and PTK7 loss-of-function migration defects can be rescued by Ror2 expression but not by a kinase-dead Ror2 mutant, indicating the kinase function of Ror2 is required when substituting for PTK7. PTK7 loss-of-function reduces cell protrusion formation and cell motility in neural crest explants. Co-immunoprecipitation in Xenopus, morpholino knockdown, live cell imaging of neural crest explants, kinase-dead Ror2 rescue experiment PLoS One Medium 26680417
2010 The chuzhoi (chz) splice-site mutation inserts three amino acids into PTK7 between the 5th and 6th Ig-like domains, reduces membrane localization of PTK7 protein, and causes craniorachischisis, heart/lung defects, and abnormal inner ear hair cell polarity. Chuzhoi shows genetic interaction with Vangl2Lp and Celsr1Crsh, confirming PCP pathway involvement. ENU mutagenesis screen, positional cloning, immunofluorescence/immunoblot of PTK7 membrane localization, genetic epistasis with Vangl2Lp and Celsr1Crsh BMC Developmental Biology High 20704721
2011 The chuzhoi (chz) mutation creates an additional MT1-MMP cleavage site in PTK7, causing aberrant proteolysis that reduces membrane localization and alters cell migratory parameters. In vitro MT1-MMP cleavage assay of chz PTK7, mutagenesis, cell migration assays The Journal of Biological Chemistry Medium 21518755
2010 Soluble PTK7 (sPTK7, the extracellular domain) acts as a decoy receptor to inhibit VEGF-induced tube formation, migration, and invasion of endothelial cells and angiogenesis in vivo. sPTK7 reduces VEGF-induced phosphorylation of FAK and paxillin, blocks paxillin relocalization to focal adhesions, and inhibits stress fiber formation. PTK7 siRNA knockdown also inhibits VEGF-induced tube formation. Recombinant sPTK7 treatment, HUVEC tube formation/migration/invasion assays, siRNA knockdown, immunofluorescence of paxillin/focal adhesions, in vivo Matrigel angiogenesis assay Biochemical and Biophysical Research Communications Medium 18471990
2015 PTK7 interacts with KDR (VEGFR2) but not FLT-1 via its extracellular domain. sPTK7 forms oligomers with the extracellular domain of KDR. At low molar ratios, sPTK7 enhances VEGF binding to KDR and promotes KDR phosphorylation/migration/tube formation; at high molar ratios or high cellular PTK7 levels, sPTK7 inhibits VEGF-KDR binding and angiogenic phenotypes (biphasic regulation). Co-immunoprecipitation, in vitro binding assay, KDR phosphorylation assays in HUVECs, VEGF binding competition, angiogenesis in vivo Biochimica et Biophysica Acta Medium 25986862
2016 PTK7 knockdown in esophageal squamous cell carcinoma (ESCC) cells reduces MMP-9 secretion by decreasing phosphorylation of NF-κB, IκB, ERK, and JNK, and blocking nuclear localization of NF-κB and AP-1 (c-Fos/c-Jun). NF-κB activation by PTK7 involves the PI3K/Akt pathway and requires Src kinase activity. PTK7 siRNA knockdown, gelatin zymography, MMP9 luciferase reporter, phospho-immunoblotting, nuclear fractionation, pharmacological inhibitors Oncotarget Medium 27689325
2019 PTK7 binds FGFR1 via its extracellular domain in ESCC and HEK293 cells, colocalizes with FGFR1, and activates FGFR1 phosphorylation independent of FGF ligand. PTK7 knockdown reduces both ligand-free and FGF-induced FGFR1 phosphorylation and downstream signaling, and inhibits FGF-induced oncogenic phenotypes. Co-immunoprecipitation, co-localization imaging, PTK7 knockdown, FGFR1 phosphorylation assays with/without FGF, proliferation/invasion/wound-healing assays FASEB Journal Medium 31490704
2017 In the presence of canonical Wnt ligands, PTK7 undergoes caveolin-mediated endocytosis (not triggered by non-canonical Wnt ligands), dependent on co-receptor Fzd7, leading to lysosomal degradation of PTK7. This suggests mutual inhibition: PTK7 suppresses canonical Wnt signaling while canonical Wnt induces PTK7 internalization and degradation. Endocytosis assays, caveolin inhibition, Fzd7 loss-of-function, lysosomal inhibitor treatment, immunofluorescence, Wnt reporter assays in Xenopus Journal of Cell Science Medium 28420671
2010 PTK7 expression in AML cells promotes cell migration, cell survival, and resistance to anthracycline-induced apoptosis; the intracellular region of PTK7 is required for these effects. A recombinant soluble PTK7-Fc protein sensitizes primary AML blasts to anthracycline-mediated cell death. PTK7 overexpression in leukemia cell lines, soluble PTK7-Fc decoy treatment, cell migration assay, apoptosis assay, domain deletion (intracellular region requirement) Blood Medium 20558616
2014 PTK7 expression in cancer cells regulates cell motility in a two-dimensional versus three-dimensional environment differently depending on its proteolytic processing. Both overexpression and knockout of PTK7 in HT1080 cells abrogate metastatic dissemination in mouse and chick embryo models. PTK7 levels and cleavage by MT1-MMP are both required for efficient directional cell motility. PTK7 overexpression and knockout in HT1080 cells, mouse/chick embryo metastasis models, analysis of lamellipodia/invadopodia structure, analysis of human colorectal cancer tissue The Journal of Biological Chemistry Medium 25006253
2010 PlexinA1 interacts with PTK7 by Co-IP and shows phenotypic interaction in Xenopus co-injection experiments. PlexinA1 is required for neural crest migration and likely acts through interaction with PTK7. Co-immunoprecipitation, morpholino knockdown, co-injection epistasis in Xenopus Biochemical and Biophysical Research Communications Low 20946874
2014 In zebrafish, ptk7 mutants (Zptk7) develop idiopathic scoliosis-like spinal curvature (no vertebral malformation), while maternal-zygotic ptk7 mutants develop vertebral anomalies associated with congenital scoliosis. A human IS patient PTK7 variant disrupts PTK7 function, linking dysregulated Wnt signaling to scoliosis pathogenesis. Zebrafish ptk7 genetic mutants (ZFN), MZ mutant analysis, microCT imaging of vertebral column, functional analysis of human variant Nature Communications High 25182715
2023 Secreted N-terminal domain of PTK7 (from senescent fibroblasts as a SASP component) activates non-canonical Wnt/Ca2+ signaling through FZD7 in intestinal stem cells. PTK7-induced changes in cytosolic Ca2+ promote nuclear translocation of YAP and induce YAP/TEAD target gene expression, impairing symmetry breaking and stem cell differentiation. Intestinal organoid assay, SASP conditioned medium fractionation, PTK7 neutralization, Ca2+ imaging, YAP nuclear translocation assay, FZD7 knockdown epistasis Nature Communications High 36631445
2023 PTK7 is an extracellular binding partner of the adhesion GPCR GPR133 (ADGRD1) in glioblastoma, identified by affinity proteomics. PTK7 binds the autoproteolytically generated N-terminal fragment of GPR133 and acts as a positive allosteric modulator of GPR133 signaling in trans. This effect requires GPR133 intramolecular cleavage and PTK7 membrane anchoring. PTK7 and GPR133 are expressed in adjacent cells in glioblastoma and their knockdowns phenocopy each other. Affinity proteomics (BioID), Co-IP, GPR133 signaling assays, domain deletion (GPR133 cleavage mutant, PTK7 membrane anchor), siRNA knockdown in glioblastoma cells Cell Reports High 37354459
2022 PTK7 interacts with and stabilizes NDRG1 (predominantly adjacent to adherens junctions) as identified by BirA*-PTK7 proximity labeling. Downregulation of PTK7 or NDRG1 eliminates AZD9291 (osimertinib) resistance in NSCLC cells, and PTK7 knockdown or overexpression alters cell-cell adhesion strength, linking PTK7-NDRG1 axis to drug resistance. Phosphoproteomics, proximity labeling (BirA*-PTK7), Co-IP, PTK7 knockdown/overexpression, drug sensitivity assays ACS Chemical Biology Medium 36205702
2024 The binding site of DNA aptamer sgc8c on PTK7 is within Ig domains 3–4 of the extracellular domain, confirmed by sequential protein truncation and crystal structure of the sgc8c–Ig(3-4) complex. Specific PTK7 amino acid residues and aptamer nucleotide residues mediating binding were identified by mass spectrometry, molecular dynamics simulation, and mutagenesis. Protein truncation, crystal structure determination, mass spectrometry footprinting, molecular dynamics simulation, mutagenesis Analytical Chemistry High 38889444
2014 In zebrafish, ptk7 regulates Id1 expression in CD44-high glioma cells through TGF-β/Smad signaling. PTK7 knockdown reduces Id1 expression and attenuates TGF-β-stimulated cell proliferation; overexpression of Id1 restores proliferation impaired by PTK7 depletion. Lentiviral shRNA knockdown, gene expression microarray, Id1 rescue overexpression, TGF-β/Smad pathway inhibition, orthotopic mouse model Neuro-Oncology Medium 25204555
1996 Human PTK7 encodes a 1,070 amino acid receptor protein tyrosine kinase-like polypeptide (closely related to chick KLG) with several unusual residues in the conserved tyrosine kinase motifs, identifying it as a catalytically atypical/defective receptor tyrosine kinase. Full-length cDNA cloning, sequence analysis, expression profiling by Northern blot Journal of Biochemistry Medium 8882711
2004 Mouse PTK7 protein is not phosphorylated by itself nor by other protein tyrosine kinases, and its expression does not affect cellular phosphotyrosine levels, confirming it is a catalytically inactive (defective) receptor tyrosine kinase. In vitro kinase assay, phosphotyrosine immunoblot in COS-1 cells expressing mouse PTK7 Gene Medium 15019986
2019 PTK7 variants associated with neural tube defects (NTDs): p.Arg630Ser increases PTK7 interaction with Dvl2, while p.Thr186Met decreases PTK7 interaction with Dvl2, as demonstrated by co-immunoprecipitation; p.Arg630Ser also affects PTK7 protein stability. Sequencing of NTD patients, immunoblotting (protein stability), co-immunoprecipitation (PTK7–Dvl2 interaction), validation in Chinese NTD cohort Molecular Genetics & Genomic Medicine Medium 30689296
2022 PTK7 modulates Rho-GTPase signaling and cell adhesion to sustain epithelial-mesenchymal transition (EMT) and cell plasticity in ovarian cancer. Phosphoproteomics upon PTK7 knockdown identified downstream effectors SNCG, SALL2, and PP1γ, and confirmed modulation of Rho-GTPase signaling pathways. PTK7 siRNA knockdown, proteomics and phosphoproteomics, 3D high-content imaging, ex vivo primary samples with cofetuzumab mAb, drug sensitivity testing Cell Death & Disease Medium 35977930
2023 PTK7 interacts with FGFR1 and EGFR (extracellular domain interactions) in triple-negative breast cancer cells. PTK7 knockdown decreases growth-factor-induced phosphorylation of both FGFR1 and EGFR, and reduces ERK, Akt, and FAK phosphorylation, indicating PTK7 modulates oncogenic RTK activation. Co-immunoprecipitation, siRNA knockdown, phospho-immunoblotting, proliferation/migration/invasion assays International Journal of Molecular Sciences Medium 37569547

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. Nature 409 15229603
2017 A PTK7-targeted antibody-drug conjugate reduces tumor-initiating cells and induces sustained tumor regressions. Science translational medicine 136 28077676
2014 ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease. Nature communications 123 25182715
2008 PTK7 recruits dsh to regulate neural crest migration. Development (Cambridge, England) 116 19004858
2009 PTK7 is essential for polarized cell motility and convergent extension during mouse gastrulation. Development (Cambridge, England) 112 19439496
1997 Loss of expression of receptor tyrosine kinase family genes PTK7 and SEK in metastatic melanoma. International journal of cancer 110 9185712
2011 PTK7/Otk interacts with Wnts and inhibits canonical Wnt signalling. The EMBO journal 108 21772251
2013 Ptk7 promotes non-canonical Wnt/PCP-mediated morphogenesis and inhibits Wnt/β-catenin-dependent cell fate decisions during vertebrate development. Development (Cambridge, England) 104 23533179
2012 The many roles of PTK7: a versatile regulator of cell-cell communication. Archives of biochemistry and biophysics 89 22230326
2015 The PTK7 and ROR2 Protein Receptors Interact in the Vertebrate WNT/Planar Cell Polarity (PCP) Pathway. The Journal of biological chemistry 86 26499793
2010 The cell polarity PTK7 receptor acts as a modulator of the chemotherapeutic response in acute myeloid leukemia and impairs clinical outcome. Blood 85 20558616
2010 The novel mouse mutant, chuzhoi, has disruption of Ptk7 protein and exhibits defects in neural tube, heart and lung development and abnormal planar cell polarity in the ear. BMC developmental biology 84 20704721
2010 The Wnt/planar cell polarity protein-tyrosine kinase-7 (PTK7) is a highly efficient proteolytic target of membrane type-1 matrix metalloproteinase: implications in cancer and embryogenesis. The Journal of biological chemistry 79 20837484
2011 RACK1 is a novel interaction partner of PTK7 that is required for neural tube closure. Development (Cambridge, England) 76 21350015
2017 PTK7 Faces the Wnt in Development and Disease. Frontiers in cell and developmental biology 72 28424771
2008 Soluble PTK7 inhibits tube formation, migration, and invasion of endothelial cells and angiogenesis. Biochemical and biophysical research communications 68 18471990
2016 Wnt, Ptk7, and FGFRL expression gradients control trunk positional identity in planarian regeneration. eLife 67 27074666
1984 Effects of cholecystokinin (CCK)-4, nonsulfated CCK-8, and sulfated CCK-8 on pancreatic somatostatin, insulin, and glucagon secretion in the dog: studies in vitro. Endocrinology 67 6143659
2010 Silencing of PTK7 in colon cancer cells: caspase-10-dependent apoptosis via mitochondrial pathway. PloS one 64 21103379
2013 PTK7 modulates Wnt signaling activity via LRP6. Development (Cambridge, England) 63 24353057
2012 The cytosolic domain of protein-tyrosine kinase 7 (PTK7), generated from sequential cleavage by a disintegrin and metalloprotease 17 (ADAM17) and γ-secretase, enhances cell proliferation and migration in colon cancer cells. The Journal of biological chemistry 59 22665490
2012 PTK7 regulates myosin II activity to orient planar polarity in the mammalian auditory epithelium. Current biology : CB 56 22560610
2001 Vigabatrin decreases cholecystokinin-tetrapeptide (CCK-4) induced panic in healthy volunteers. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 56 11682253
1996 Characterization of the human full-length PTK7 cDNA encoding a receptor protein tyrosine kinase-like molecule closely related to chick KLG. Journal of biochemistry 54 8882711
2023 Senescent cells perturb intestinal stem cell differentiation through Ptk7 induced noncanonical Wnt and YAP signaling. Nature communications 53 36631445
2021 PTK7-Targeting CAR T-Cells for the Treatment of Lung Cancer and Other Malignancies. Frontiers in immunology 53 34475869
2014 Protein-tyrosine pseudokinase 7 (PTK7) directs cancer cell motility and metastasis. The Journal of biological chemistry 53 25006253
2015 Isolation of Human Colon Stem Cells Using Surface Expression of PTK7. Stem cell reports 51 26549850
2015 Overexpression of the Promigratory and Prometastatic PTK7 Receptor Is Associated with an Adverse Clinical Outcome in Colorectal Cancer. PloS one 49 25962058
2014 PTK7-Src signaling at epithelial cell contacts mediates spatial organization of actomyosin and planar cell polarity. Developmental cell 49 24703874
2012 PTK7: a new biomarker for immunophenotypic characterization of maturing T cells and T cell acute lymphoblastic leukemia. Leukemia research 49 22898210
2011 Cdx mediates neural tube closure through transcriptional regulation of the planar cell polarity gene Ptk7. Development (Cambridge, England) 49 21350009
1991 CCK-8, CCK-4 and gastrin-induced contractions in guinea pig ileum: evidence for differential release of acetylcholine and substance P by CCK-A and CCK-B receptors. The Journal of pharmacology and experimental therapeutics 48 1704435
2012 PTK7 as a novel marker for favorable gastric cancer patient survival. Journal of surgical oncology 44 22585737
1995 Ac-[3- and 4-alkylthioproline31]-CCK4 analogs: synthesis and implications for the CCK-B receptor-bound conformation. Journal of medicinal chemistry 44 7837225
2007 Comparative integromics on non-canonical WNT or planar cell polarity signaling molecules: transcriptional mechanism of PTK7 in colorectal cancer and that of SEMA6A in undifferentiated ES cells. International journal of molecular medicine 40 17671748
2007 Role of the amygdaloid cholecystokinin (CCK)/gastrin-2 receptors and terminal networks in the modulation of anxiety in the rat. Effects of CCK-4 and CCK-8S on anxiety-like behaviour and [3H]GABA release. The European journal of neuroscience 38 18088282
2019 Variants identified in PTK7 associated with neural tube defects. Molecular genetics & genomic medicine 35 30689296
2016 Catalytically defective receptor protein tyrosine kinase PTK7 enhances invasive phenotype by inducing MMP-9 through activation of AP-1 and NF-κB in esophageal squamous cell carcinoma cells. Oncotarget 35 27689325
2011 PTK7: a cell polarity receptor with multiple facets. Cell cycle (Georgetown, Tex.) 35 21415598
2005 Panic induction with cholecystokinin-tetrapeptide (CCK-4) Increases plasma concentrations of the neuroactive steroid 3alpha, 5alpha tetrahydrodeoxycorticosterone (3alpha, 5alpha-THDOC) in healthy volunteers. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 35 15467707
2002 Organization of the human PTK7 gene encoding a receptor protein tyrosine kinase-like molecule and alternative splicing of its mRNA. Biochimica et biophysica acta 35 12427550
2014 The PTK7-related transmembrane proteins off-track and off-track 2 are co-receptors for Drosophila Wnt2 required for male fertility. PLoS genetics 34 25010066
2013 PTK7 expression in triple-negative breast cancer. Anticancer research 34 24023307
2005 The GxxxG-containing transmembrane domain of the CCK4 oncogene does not encode preferential self-interactions. Biochemistry 34 15683231
2004 Cloning and characterization of the full-length mouse Ptk7 cDNA encoding a defective receptor protein tyrosine kinase. Gene 33 15019986
1997 The cholecystokinin-B receptor antagonist CI-988 failed to affect CCK-4 induced symptoms in panic disorder patients. Psychopharmacology 33 9084062
2014 PTK7 regulates Id1 expression in CD44-high glioma cells. Neuro-oncology 31 25204555
2017 PTK7 localization and protein stability is affected by canonical Wnt ligands. Journal of cell science 30 28420671
2024 Structure-based investigation of a DNA aptamer targeting PTK7 reveals an intricate 3D fold guiding functional optimization. Proceedings of the National Academy of Sciences of the United States of America 28 38985770
2021 Inhibition of BCL11B induces downregulation of PTK7 and results in growth retardation and apoptosis in T-cell acute lymphoblastic leukemia. Biomarker research 28 33663588
2016 Development of new PTK7-targeting aptamer-fluorescent and -radiolabelled probes for evaluation as molecular imaging agents: Lymphoma and melanoma in vivo proof of concept. Bioorganic & medicinal chemistry 28 28089349
2012 Insights into ectodomain shedding and processing of protein-tyrosine pseudokinase 7 (PTK7). The Journal of biological chemistry 28 23095747
2016 Ptk7 and Mcc, Unfancied Components in Non-Canonical Wnt Signaling and Cancer. Cancers 27 27438854
2010 PlexinA1 interacts with PTK7 and is required for neural crest migration. Biochemical and biophysical research communications 27 20946874
2005 Randomized, double-blind study of SR142801 (Osanetant). A novel neurokinin-3 (NK3) receptor antagonist in panic disorder with pre- and posttreatment cholecystokinin tetrapeptide (CCK-4) challenges. Pharmacopsychiatry 26 15706463
2018 miR‑205‑5p/PTK7 axis is involved in the proliferation, migration and invasion of colorectal cancer cells. Molecular medicine reports 25 29488611
2014 Downstream signaling and genome-wide regulatory effects of PTK7 pseudokinase and its proteolytic fragments in cancer cells. Cell communication and signaling : CCS 24 24618420
2019 The Increased PTK7 Expression Is a Malignant Factor in Cervical Cancer. Disease markers 23 30944666
2011 Potential relation of aberrant proteolysis of human protein tyrosine kinase 7 (PTK7) chuzhoi by membrane type 1 matrix metalloproteinase (MT1-MMP) to congenital defects. The Journal of biological chemistry 23 21518755
2015 Biphasic effect of PTK7 on KDR activity in endothelial cells and angiogenesis. Biochimica et biophysica acta 22 25986862
2015 A PTK7/Ror2 Co-Receptor Complex Affects Xenopus Neural Crest Migration. PloS one 22 26680417
2024 Recent insights into the therapeutic strategies targeting the pseudokinase PTK7 in cancer. Oncogene 21 38773263
2023 A dual-ratio fluorescent probe with a single excitation triple-signal to synchronously detect PTK7 and miRNA-21 for breast cancer early diagnosis. Biosensors & bioelectronics 20 37480788
2022 Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate. Biomaterials research 20 36471380
2020 LncRNA-MALAT1 regulates proliferation and apoptosis of acute lymphoblastic leukemia cells via miR-205-PTK7 pathway. Pathology international 20 32754978
2016 Ptk7-Deficient Mice Have Decreased Hematopoietic Stem Cell Pools as a Result of Deregulated Proliferation and Migration. Journal of immunology (Baltimore, Md. : 1950) 20 27183644
2016 PTK7 regulates radioresistance through nuclear factor-kappa B in esophageal squamous cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20 27557627
2008 Association testing of panic disorder candidate genes using CCK-4 challenge in healthy volunteers. Neuroscience letters 20 18832011
2022 Multiomics characterization implicates PTK7 in ovarian cancer EMT and cell plasticity and offers strategies for therapeutic intervention. Cell death & disease 19 35977930
2022 Protein Tyrosine Kinase 7 (PTK7) Promotes Metastasis in Hepatocellular Carcinoma via SOX9 Regulation and TGF-β Signaling. Cellular and molecular gastroenterology and hepatology 19 36202326
2022 Proteomic and Phosphoproteomic Analyses Reveal the Oncogenic Role of PTK7-NDRG1 Axis in Non-small-cell Lung Cancer Cell Resistance to AZD9291. ACS chemical biology 19 36205702
2017 Therapeutic Targeting of PTK7 is Cytotoxic in Atypical Teratoid Rhabdoid Tumors. Molecular cancer research : MCR 19 28442586
2017 PTK7 is a novel oncogenic target for esophageal squamous cell carcinoma. World journal of surgical oncology 19 28545451
2002 2-Oxopiperazine-based gamma-turn conformationally constrained peptides: synthesis of CCK-4 analogues. The Journal of organic chemistry 19 12027705
2021 Metastatic and non-metastatic melanoma imaging using Sgc8-c aptamer PTK7-recognizer. Scientific reports 18 34620894
2023 Identification and targeting of protein tyrosine kinase 7 (PTK7) as an immunotherapy candidate for neuroblastoma. Cell reports. Medicine 17 37343516
2015 Neuropeptide S receptor gene variation modulates anterior cingulate cortex Glx levels during CCK-4 induced panic. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 17 26235955
2023 A novel TREM1/DAP12-based multiple chain CAR-T cell targets PTK7 in ovarian cancer therapy. Medical oncology (Northwood, London, England) 16 37405498
2024 FOXP4-mediated induction of PTK7 activates the Wnt/β-catenin pathway and promotes ovarian cancer development. Cell death & disease 15 38740744
2023 PTK7 is a positive allosteric modulator of GPR133 signaling in glioblastoma. Cell reports 15 37354459
2019 Catalytically inactive receptor tyrosine kinase PTK7 activates FGFR1 independent of FGF. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 15 31490704
2019 PTK7 expression is associated with lymph node metastasis, ALK and EGFR mutations in lung adenocarcinomas. Histology and histopathology 15 31701509
2010 CCK-4: Psychophysiological conditioning elicits features of spontaneous panic attacks. Journal of psychiatric research 14 20451215
1998 Decrease in short-term memory function induced by CCK-4 in healthy volunteers. Peptides 14 9700743
1994 Systemic administration of CCK-8S, but not CCK-4, enhances dopamine turnover in the posterior nucleus accumbens: a microdialysis study in freely moving rats. Brain research 14 7820607
2023 MTX-13, a Novel PTK7-Directed Antibody-Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors. Molecular cancer therapeutics 13 37352387
2023 Knockdown of PTK7 Reduces the Oncogenic Potential of Breast Cancer Cells by Impeding Receptor Tyrosine Kinase Signaling. International journal of molecular sciences 13 37569547
2022 Diverse ancestry whole-genome sequencing association study identifies TBX5 and PTK7 as susceptibility genes for posterior urethral valves. eLife 13 36124557
2020 PTK7 promotes the malignant properties of cancer stem-like cells in esophageal squamous cell lines. Human cell 13 31894477
2012 PTK7 marks the first human developmental EMT in vitro. PloS one 13 23209741
2006 Tryptophan depletion does not modify response to CCK-4 challenge in patients with panic disorder after treatment with citalopram. Psychopharmacology 13 16541242
2001 The influence of Type A behavior pattern on the response to the panicogenic agent CCK-4. Journal of psychosomatic research 13 11602221
2021 The Mutational Landscape of PTK7 in Congenital Scoliosis and Adolescent Idiopathic Scoliosis. Genes 12 34828397
2005 Conformationally constrained CCK4 analogues incorporating IBTM and BTD beta-turn mimetics. Journal of medicinal chemistry 12 16302807
2020 Identification of PTK7 as a promising therapeutic target for thyroid cancer. European review for medical and pharmacological sciences 11 32633373
2010 Glyoxalase-I mRNA expression and CCK-4 induced panic attacks. Journal of psychiatric research 11 20542521
2024 Identification of the Binding Site between Aptamer sgc8c and PTK7. Analytical chemistry 10 38889444
2024 PTK7: an underestimated contributor to human cancer. Frontiers in oncology 10 39474113
2022 Anti-PTK7 Monoclonal Antibodies Inhibit Angiogenesis by Suppressing PTK7 Function. Cancers 10 36139622

Missed literature

Know a paper Affinage missed for PTK7? Flag it for the maintainers and the community.

No submissions yet.