Affinage

PTPN14

Tyrosine-protein phosphatase non-receptor type 14 · UniProt Q15678

Length
1187 aa
Mass
135.3 kDa
Annotated
2026-06-10
58 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTPN14 is an evolutionarily conserved FERM domain–containing non-receptor protein tyrosine phosphatase that acts as a central negative regulator of the Hippo pathway effector YAP, coupling cell-density and growth-state cues to growth suppression (PMID:7733990, PMID:22948661, PMID:22525271). Its dominant mechanism is non-catalytic: PTPN14 binds YAP through reciprocal PPxY–WW interactions and, by binding the upstream component Kibra, cooperatively activates and stabilizes LATS1 kinase independently of MST1/2, driving LATS1-dependent YAP phosphorylation (YAP1 S127), cytoplasmic sequestration, and loss of YAP transcriptional output (PMID:22948661, PMID:22525271, PMID:25023289, PMID:39248565). This scaffold function requires PTPN14's PPxY motifs but not its phosphatase active site (PMID:23613971, PMID:39248565). PTPN14 localization is growth-state-dependent, residing in the nucleus in proliferating/low-density cells and at the cytoplasm/adherens junctions in confluent monolayers, with NPM1 retaining it in the nucleus under hypoxia to release YAP (PMID:10934049, PMID:12808048, PMID:35135548). In parallel, PTPN14 acts as a bona fide tyrosine phosphatase on multiple substrates, dephosphorylating β-catenin at adherens junctions (PMID:12808048), VE-cadherin at Tyr-658 to restore endothelial barrier function (PMID:32327488), PDGFRβ at Tyr-692 to restrain smooth-muscle phenotypic switching (PMID:39191789), RIN1 and PRKCD to limit secretory trafficking and metastasis (PMID:25690013), and BCAR3 to suppress PI3K/AKT and ERK signaling (PMID:39189475). PTPN14 protein levels are tightly controlled by ubiquitin ligases—CRL2(LRR1) at low density and WWP1/Su(dx) via its PPxY motifs—while high-risk HPV E7 oncoproteins co-opt UBR4 to degrade PTPN14 through a high-affinity C-terminal interaction with the phosphatase domain, impairing keratinocyte differentiation and, together with RB1 inactivation, immortalizing keratinocytes (PMID:22948661, PMID:25814387, PMID:27651363, PMID:31323018, PMID:41890011). Loss-of-function mutations in PTPN14 cause autosomal-recessive lymphedema-choanal atresia syndrome, and PTPN14 is a p53-induced tumor suppressor of pancreatic cancer acting through YAP (PMID:20826270, PMID:29017057).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 Medium

    Establishing PTPN14's domain architecture defined it as a candidate cytoskeleton/membrane-associated phosphatase, framing all later mechanistic work.

    Evidence cDNA cloning, sequence analysis and FISH mapping of a FERM-PTP protein

    PMID:7733990

    Open questions at the time
    • No substrate or pathway assigned at this stage
    • FERM-domain binding partners not identified
  2. 2000 Medium

    Linking PTPN14 localization to proliferation state revealed that its function is regulated by a nuclear-cytoplasmic switch tied to cell density.

    Evidence Subcellular fractionation, immunofluorescence and density/wound assays in endothelial cells

    PMID:10934049

    Open questions at the time
    • Molecular driver of the localization switch unknown
    • Functional output of localization not defined
  3. 2003 High

    Identifying β-catenin as a direct substrate at adherens junctions provided the first catalytic substrate and connected PTPN14 to junctional integrity and motility.

    Evidence Substrate trapping, in vitro dephosphorylation with recombinant enzyme, dominant-negative motility assay

    PMID:12808048

    Open questions at the time
    • Did not address Hippo/YAP regulation
    • In vivo relevance not tested
  4. 2007 Medium

    Demonstrating that PTPN14 perturbation drives EMT and organogenesis defects established it as a developmental regulator linked to TGFβ signaling.

    Evidence Overexpression in MDCK cells and morpholino knockdown in zebrafish

    PMID:17893246

    Open questions at the time
    • Mechanism connecting PTPN14 to TGFβ unresolved
    • No molecular substrate linked to the phenotype
  5. 2010 High

    Human genetics and mouse models tied PTPN14 loss to lymphedema-choanal atresia and lymphatic hyperplasia, with a VEGFR3 interaction giving a candidate mechanism.

    Evidence Genetic linkage/sequencing, gene-trap mouse, co-immunoprecipitation

    PMID:20826270

    Open questions at the time
    • Whether VEGFR3 is a phosphatase substrate not established
    • Causal pathway from interaction to lymphatic phenotype incomplete
  6. 2012 High

    Convergent studies placed PTPN14 as a YAP-binding negative regulator that promotes YAP cytoplasmic localization during contact inhibition, with density-dependent stability controlled by CRL2(LRR1).

    Evidence shRNA screen, Co-IP with domain mapping, fractionation, luciferase reporter and E3 ligase identification across multiple labs

    PMID:22305752 PMID:22525271 PMID:22948661

    Open questions at the time
    • Whether YAP regulation requires phosphatase catalysis was disputed
    • Upstream kinase mediating the effect not yet defined
  7. 2013 High

    Showing that the PPxY motif and phosphatase activity are dispensable for endogenous YAP regulation reframed PTPN14 as a scaffold rather than a YAP-directed enzyme.

    Evidence Domain/motif and active-site mutants, transformation assays, siRNA in mammary epithelial cells

    PMID:23613971

    Open questions at the time
    • Identity of the activated kinase still unknown at this point
    • Reconciliation with earlier direct-substrate claims left open
  8. 2014 High

    Identifying the PTPN14-Kibra-LATS1 axis explained how PTPN14 represses YAP without MST kinases, by cooperatively activating and stabilizing LATS1.

    Evidence Co-IP, kinase activity assays, 3D morphogenesis and migration rescue with Kibra

    PMID:25023289

    Open questions at the time
    • Structural basis of LATS1 activation not resolved
    • Quantitative contribution of scaffolding vs. stability unclear
  9. 2015 High

    Two studies defined PTPN14 stability control by WWP1/Su(dx) via PPxY motifs and revealed catalytic suppression of secretory trafficking through RIN1 and PRKCD dephosphorylation.

    Evidence Degradation assays with domain mapping in Drosophila/mammalian cells; substrate identification, phosphomutant rescue, xenografts

    PMID:25690013 PMID:25814387

    Open questions at the time
    • Coordination between scaffold and catalytic functions not integrated
    • How trafficking substrates relate to YAP control unaddressed
  10. 2017 High

    High-risk HPV E7 was shown to drive UBR4-dependent PTPN14 degradation via a C-terminal E7–phosphatase-domain interaction, establishing PTPN14 as an RB1-independent E7 target controlling differentiation and immortalization, and p53 was shown to act through Ptpn14 to suppress pancreatic cancer.

    Evidence Co-IP, proteasome/cullin and UBR4 knockdown, E7 separation-of-function variants, p53 mouse cancer model and human mutual-exclusivity analysis

    PMID:27651363 PMID:28100625 PMID:29017057 PMID:30894485

    Open questions at the time
    • Whether PTPN14 catalytic activity matters for the HPV phenotypes not yet pinned down
    • Downstream effectors of the p53-PTPN14-YAP axis incompletely mapped
  11. 2018 Medium

    Identifying Roquin2 Tyr-691 as a catalytic substrate linked PTPN14 dephosphorylation to control of an mRNA-decay factor via its E3 ligase interaction.

    Evidence Co-IP, mass spectrometry, phospho-site mapping, KLHL6-dependent degradation assay

    PMID:30209976

    Open questions at the time
    • Single lab, limited independent replication
    • Physiological context of Roquin2 regulation not established
  12. 2019 High

    A crystal structure of HPV18 E7 bound to the PTPN14 phosphatase domain (Kd 18.2 nM) defined the degradation interface and enabled separation-of-function mutants showing E7-resistant PTPN14 better inhibits Hippo effectors; a parallel study placed PTPN14-YAP upstream of SMAD3/TGFβ signaling in synoviocytes.

    Evidence X-ray crystallography, SPR, structure-guided mutagenesis; Co-IP, SMAD reporter and disease model with non-YAP-binding mutant

    PMID:30808624 PMID:31323018

    Open questions at the time
    • How E7 binding to the catalytic domain alters phosphatase function not detailed
    • TGFβ/SMAD link mechanistically shallow
  13. 2020 High

    Multiple substrates and partners were established, defining PTPN14 catalytic roles in endothelial barrier recovery (VE-cadherin Tyr-658), an NPM1-driven nuclear retention mechanism under hypoxia that releases YAP, an inflammatory PTPN14-SOCS7-NF-κB axis, and a conserved C-terminal arginine in E7 required for PTPN14 binding/degradation.

    Evidence Phospho-site-specific antibodies, Co-IP, PLD2 manipulation, in vivo permeability/liver-failure models, E7 arginine mutants with CRISPR rescue

    PMID:32327488 PMID:32581101 PMID:32978373 PMID:35135548

    Open questions at the time
    • Whether SOCS7 ubiquitination is direct vs. indirect unclear
    • Integration of catalytic substrate roles with scaffold-YAP role incomplete
  14. 2024 High

    New substrates (PDGFRβ Tyr-692, BCAR3) and a definitive scaffold-mechanism study clarified that PTPN14 controls keratinocyte differentiation through LATS1-dependent YAP phosphorylation requiring its PPxY motifs but not its catalytic site, while also using catalysis to restrain SMC switching and anoikis resistance.

    Evidence Phospho-site antibodies, SMC conditional KO/OE mice, genome-wide CRISPR screen, LATS1/2 KO and active-site/PPxY mutants in keratinocytes

    PMID:39189475 PMID:39191789 PMID:39248565

    Open questions at the time
    • What dictates choice between scaffold vs. catalytic mode in a given tissue
    • Mechanism of LATS1 phosphorylation by the scaffold not resolved
  15. 2025 High

    In vivo knockout revealed sexually dimorphic, YAP-dependent tissue phenotypes; small-molecule (fenofibrate) engagement of the PPxY motif assembling a PTPN14/LATS1/MARK3 complex demonstrated pharmacological exploitability; RB1 and PTPN14 inactivation were shown to be jointly required for HPV E7 immortalization.

    Evidence Constitutive KO mouse histopathology/YAP IF; direct PPxY binding and complex Co-IP with functional knockdown; E7 separation-of-function complementation (preprint)

    PMID:40533389 PMID:40858196 PMID:41890011

    Open questions at the time
    • Basis of female-specific phenotypes unexplained
    • Role of MARK3 in physiological PTPN14-LATS1 signaling not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PTPN14's scaffold (LATS1-activating) and catalytic (multi-substrate) functions are selected and integrated within a given cell, and what determines its nuclear-cytoplasmic partitioning beyond density and hypoxia, remain unresolved.
  • No unified model coupling localization to catalytic vs. scaffold output
  • Structural mechanism of LATS1 activation by the PTPN14-Kibra scaffold unknown
  • Tissue determinants of substrate selection uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016787 hydrolase activity 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-1266738 Developmental Biology 2
Partners
LATS1NPM1PDGFRBPRKCDRIN1VEGFR3WWBP2/KIBRAYAP1
Complex memberships
PTPN14-Kibra-LATS1 complexPTPN14-VE-cadherin-PLD2 junctional complexPTPN14/LATS1/MARK3 complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 PTPN14 (Pez) was identified as a novel non-receptor protein tyrosine phosphatase with N-terminal FERM domain homology (ezrin/band 4.1/merlin/radixin family) and a C-terminal PTP catalytic domain, encoded on chromosome 1q32.2-41. cDNA cloning, sequence analysis, Northern blot, FISH mapping Biochemical and biophysical research communications Medium 7733990
2000 PTPN14 (Pez) localizes to the nucleus in proliferating/low-density endothelial cells and translocates to the cytoplasm in confluent quiescent monolayers; TGFβ inhibited nuclear translocation at wound edges, linking nuclear localization to cell proliferation. Subcellular fractionation, immunofluorescence, density manipulation, serum starvation/refeeding, wound assay Journal of cell science Medium 10934049
2003 PTPN14 (Pez) localizes to adherens junctions in confluent epithelial cells and directly dephosphorylates β-catenin; a catalytic-domain truncation dominant-negative mutant increased tyrosine phosphorylation at adherens junctions and enhanced cell motility. Immunofluorescence, substrate-trapping approach, in vitro dephosphorylation with recombinant Pez, dominant-negative overexpression, wound motility assay Molecular biology of the cell High 12808048
2007 PTPN14 (Pez) overexpression in epithelial MDCK cells induces EMT accompanied by induction of TGFβ signaling; Pez knockdown in zebrafish disrupts organogenesis (brain, heart, pharyngeal arches, somites) and abolishes TGFβ3 expression from co-expressing tissues. Overexpression in MDCK cells (morphology, gene expression), morpholino knockdown in zebrafish, in situ hybridization The Journal of cell biology Medium 17893246
2010 Loss-of-function mutation in PTPN14 causes autosomal-recessive lymphedema-choanal atresia syndrome; Ptpn14 gene-trap mice develop lymphatic hyperplasia with lymphedema; PTPN14 biochemically interacts with VEGFR3, a receptor tyrosine kinase essential for lymphangiogenesis. Genetic linkage, Sanger sequencing, murine gene-trap model (lymphatic phenotype), co-immunoprecipitation/biochemical interaction studies American journal of human genetics High 20826270
2012 PTPN14 interacts with YAP1 (via PTPN14 PPxY domain and YAP1 WW domain) and promotes nucleus-to-cytoplasm translocation of YAP1 during contact inhibition, suppressing YAP1 transcriptional activity; PTPN14 protein stability is positively regulated by cell density, and the CRL2(LRR1) E3 ubiquitin ligase complex targets PTPN14 for degradation at low cell density. shRNA screen, co-immunoprecipitation, subcellular fractionation/localization assays, luciferase reporter, ubiquitin ligase identification Genes & development High 22948661
2012 PTPN14 directly interacts with YAP through the WW domain of YAP and the PPxY domain of PTPN14; YAP is a direct substrate of PTPN14 phosphatase activity; PTPN14 inhibits YAP transcriptional co-activator function and increases cytoplasmic YAP; PTPN14 knockdown induces nuclear retention of YAP and increases YAP-dependent cell migration. Co-immunoprecipitation, luciferase reporter assay, immunofluorescence, siRNA knockdown, migration assay Oncogene High 22525271
2012 Drosophila Pez (ortholog of PTPN14) acts as a negative upstream regulator of Yorkie (YAP ortholog) specifically in the fly midgut epithelium by binding the upstream Hippo component Kibra; the PTP catalytic domain of Pez is dispensable for Hippo pathway activity in this context. Genetic loss-of-function in Drosophila, co-immunoprecipitation (Pez-Kibra interaction), ISC proliferation assays, PTP domain mutant analysis Current biology : CB High 22305752
2013 PTPN14 negatively regulates YAP activity by controlling its cytoplasmic localization; the WW/PPxY interaction between PTPN14 and YAP mediates their binding, but the PPxY motif and phosphatase activity of PTPN14 are dispensable for regulation of endogenous YAP; PTPN14 downregulation phenocopies YAP activation and synergizes with YAP to induce oncogenic transformation in mammary epithelial cells. Co-immunoprecipitation, immunofluorescence, domain/motif mutants, transformation assays, siRNA knockdown PloS one High 23613971
2014 PTPN14 interacts with Kibra through PTPN14's PPXY domain and Kibra's WW domain; PTPN14 and Kibra each independently and cooperatively activate LATS1 kinase (in a manner independent of MST kinases); PTPN14 increases LATS1 protein stability; Kibra overexpression rescues the increased cell migration and aberrant 3D morphogenesis caused by PTPN14 knockdown via LATS1-mediated YAP cytoplasmic sequestration. Co-immunoprecipitation, kinase activity assays, siRNA knockdown, 3D morphogenesis assay, migration assay, immunoblot The Journal of biological chemistry High 25023289
2015 PTPN14 suppresses metastasis by reducing protein trafficking through the secretory pathway; loss of catalytically functional PTPN14 increases secretion of IL-8 and surface abundance of EGFR and FLT4/VEGFR3; PTPN14 directly binds and dephosphorylates RIN1 and PRKCD; RIN1 dephosphorylation or PRKCD loss mimics PTPN14 overexpression in restricting receptor trafficking. shRNA knockdown, mouse xenograft model, co-immunoprecipitation, substrate identification (phosphoproteomics/pulldown), phosphomutant rescue, cytokine secretion assays, EGFR/FLT4 surface abundance measurements Science signaling High 25690013
2015 Suppressor of Deltex (Su(dx)) E3 ubiquitin ligase targets Drosophila Pez (PTPN14 ortholog) for degradation via WW domain–PY/PPxY motif interactions; Kibra stabilizes Pez through the same WW-PY/PPxY interaction; the mammalian Su(dx) homolog WWP1 similarly degrades PTPN14 in mammalian cells. In vitro and in vivo degradation assays in Drosophila, co-immunoprecipitation (WW-PPxY interaction), overexpression rescue experiments, mammalian cell WWP1 overexpression Nature communications High 25814387
2016 High-risk HPV E7 proteins target PTPN14 for proteasome-mediated degradation; this requires the E3 ubiquitin ligase UBR4; residues in the C-terminus of E7 interact with the C-terminal phosphatase domain of PTPN14; PTPN14 degradation correlates with retinoblastoma-independent transforming activity of high-risk HPV E7. Co-immunoprecipitation, proteasome inhibitor assays, UBR4 siRNA knockdown, domain mapping, transformation assays mBio High 27651363
2017 High-risk HPV E7-mediated PTPN14 degradation (proteasome-dependent, via UBR4/p600 ubiquitin ligase) impairs keratinocyte differentiation; using an HPV16 E7 variant that degrades pRb but cannot degrade PTPN14, PTPN14 degradation was shown to contribute to HPV E6/E7-mediated keratinocyte immortalization and anoikis resistance independent of RB1 inactivation. E7 variant with separated RB1/PTPN14 activities, CRISPR/primary keratinocyte culture, differentiation gene expression, anoikis/detachment survival assays Proceedings of the National Academy of Sciences of the United States of America High 30894485
2017 The p53-target gene Ptpn14 is necessary and sufficient for pancreatic cancer suppression downstream of p53; Ptpn14 negatively regulates the Yap oncoprotein; PTPN14 and TP53 mutations are mutually exclusive in human cancers, establishing a p53-Ptpn14-Yap pathway. Mouse pancreatic cancer model (p53 TAD mutants), shRNA knockdown, overexpression studies, analysis of human cancer mutation databases Cancer cell High 29017057
2017 PTPN14 interacts with HPV E7 C-terminal region independently of pRb; high-risk E7 induces proteasome-mediated PTPN14 degradation (via UBR4/p600, independent of cullin-1/cullin-2) in cervical cancer cells; PTPN14 overexpression decreases the ability of HPV-16 E7 to cooperate with activated EJ-ras in primary cell transformation. Co-immunoprecipitation, proteasome inhibitor and cullin knockdown assays, transformation/focus formation assay Journal of virology High 28100625
2018 PTPN14 specifically interacts with the mRNA decay factor Roquin2 through its phosphatase domain and dephosphorylates Roquin2 at tyrosine 691; this dephosphorylation restores the Roquin2-KLHL6 E3 ligase interaction, promoting Roquin2 proteasomal degradation. Co-immunoprecipitation, mass spectrometry identification, phospho-site mapping, in vivo phosphorylation assays, overexpression of PTPN14, KLHL6-dependent degradation assay Cell cycle (Georgetown, Tex.) Medium 30209976
2019 Crystal structure of HPV18 E7 C-terminal domain bound to PTPN14 catalytic domain was solved; the interaction has a Kd of 18.2 nM; structure-based mutagenesis of the binding interface impaired E7-promoted keratinocyte proliferation/migration and rendered PTPN14 resistant to proteasomal degradation; E7-binding-defective PTPN14 more effectively inhibited Hippo signaling downstream effectors. X-ray crystallography, surface plasmon resonance (binding affinity), structure-guided mutagenesis, cell proliferation/migration/invasion assays, immunoblot for Hippo signaling PLoS biology High 31323018
2019 In rheumatoid arthritis fibroblast-like synoviocytes (FLS), PTPN14 forms a complex with YAP and promotes nuclear localization of SMAD3 and TGFβ signaling (MMP13 expression, TNF potentiation); a non-YAP-interacting PTPN14 mutant fails to enhance SMAD reporter activity, indicating the PTPN14-YAP interaction is required for this function. Co-immunoprecipitation, antisense oligonucleotide knockdown, immunofluorescence, SMAD luciferase reporter, RA FLS-cartilage co-implantation model Annals of the rheumatic diseases Medium 30808624
2020 A conserved C-terminal arginine in diverse HPV E7 proteins mediates the interaction with PTPN14; mutation of this arginine prevents PTPN14 binding and degradation (via UBR4), renders HPV16 and HPV18 E7 unable to repress keratinocyte differentiation gene expression, and prevents HPV18 E7 from extending keratinocyte lifespan; PTPN14 CRISPR knockout rescued keratinocyte lifespan in cells expressing the PTPN14-binding-deficient E7 variant. E7 arginine mutant analysis, Co-immunoprecipitation, CRISPR/Cas9 knockout rescue experiment, differentiation gene expression assays, keratinocyte lifespan assay Journal of virology High 32581101
2020 PLD2-generated phosphatidic acid promotes PTPN14 activity; PTPN14, VE-cadherin, and PLD2 form a complex at adherens junctions after thrombin stimulation; PTPN14 dephosphorylates VE-cadherin at Tyr-658, enabling VE-cadherin recycling and endothelial barrier recovery after edemagenic insult. Co-immunoprecipitation, VE-cadherin phospho-site specific antibodies, siRNA knockdown, PLD2 inhibitor/deletion, in vivo lung permeability model The Journal of biological chemistry High 32327488
2020 PTPN14 interacts with SOCS7 and promotes its degradation via ubiquitination at K11 and K48 linkages, reducing SOCS7 protein levels; SOCS7 blocks NF-κB signaling by inhibiting IKK complex activity; PTPN14 deficiency reduces inflammation in LPS+D-GalN-induced acute liver failure via the PTPN14-SOCS7-NF-κB axis. Co-immunoprecipitation, ubiquitination assays (K11/K48 linkage-specific), PTPN14 knockout mouse model, NF-κB signaling assays Cell death & disease Medium 32978373
2022 Hypoxia-induced nuclear translocation of PTPN14 in hepatocellular carcinoma causes resistance to sorafenib; NPM1 regulates PTPN14 localization under hypoxia, retaining it in the nucleus and thereby releasing YAP from PTPN14-mediated cytoplasmic sequestration. Immunofluorescence/subcellular fractionation, siRNA knockdown, hypoxia treatment, co-immunoprecipitation (NPM1-PTPN14), HCC cell functional assays and xenograft Cancer cell international Medium 35135548
2024 PTPN14 interacts with intracellular region of PDGFRβ and dephosphorylates it at Y692; phosphorylation of PDGFRβ Y692 negatively regulates PDGFRβ signaling; PTPN14 overexpression (phosphatase activity-dependent) exacerbates neointimal hyperplasia in mice by boosting PDGFRβ signaling-induced smooth muscle cell phenotypic modulation, while SMC-specific PTPN14 deletion mitigates it. Co-immunoprecipitation, phospho-site specific antibodies (Y692), SMC-specific conditional KO mouse (neointima model), RNA-seq, overexpression studies Nature communications High 39191789
2024 PTPN14 is identified as a key regulator of anoikis resistance in triple-negative breast cancer; PTPN14 dephosphorylates BCAR3 (breast cancer antiestrogen resistance 3), leading to inhibition of PI3K/AKT and ERK signaling; PTPN14 mRNA-LNP delivery inhibited TNBC tumor growth and metastasis in vivo. Genome-wide CRISPR/Cas9 knockout screen, substrate identification (BCAR3 dephosphorylation), PI3K/AKT/ERK signaling assays, mRNA-LNP mouse xenograft Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 39189475
2024 PTPN14 knockout or HPV18 E7-mediated PTPN14 degradation decreases phosphorylation of LATS1 at T1079 and YAP1 at S127 in human keratinocytes; PTPN14-dependent differentiation requires LATS kinases and specific PPxY motifs in PTPN14 but not MST1/2 kinases or the PTPN14 phosphatase active site, placing PTPN14 as a scaffold regulator of LATS1 upstream of YAP1. PTPN14 CRISPR knockout, phospho-specific immunoblots (LATS1 T1079, YAP1 S127), LATS1/2 double knockout, PPxY motif mutants, phosphatase active-site mutants, keratinocyte differentiation assays mBio High 39248565
2025 PTPN14 knockout mice develop corneal lesions, hydrometra, heart and kidney abnormalities with only ~60% postnatal survival; the cornea shows impaired injury response and both cornea and uterus exhibit dysregulated YAP signaling; phenotypes are female-specific, revealing sexually dimorphic Hippo pathway function. Ptpn14 constitutive knockout mouse generation, histopathology, immunofluorescence for YAP, corneal injury assay Genes & development High 40533389
2025 Fenofibrate directly binds the PPxY motif of PTPN14, facilitating formation of a PTPN14/LATS1/MARK3 complex that promotes cytoplasmic sequestration of YAP; PTPN14 knockdown or MARK3 inhibition abolished fenofibrate-mediated suppression of cancer cell malignant phenotypes. Direct binding assay (PPxY motif), co-immunoprecipitation (PTPN14/LATS1/MARK3 complex), siRNA knockdown, YAP localization assays, cancer cell functional assays Pharmacological research Medium 40858196
2025 Inactivation of both RB1 and PTPN14 is required for high-risk HPV E7-mediated keratinocyte immortalization; neither RB1-binding-deficient nor PTPN14-binding-deficient E7 mutant alone could extend keratinocyte lifespan, but together they reconstituted wild-type E7 activity; PTPN14 depletion and RB1 inactivation act synergistically to induce cell cycle regulatory gene expression. Genetic complementation with E7 separation-of-function mutants (RB1-binding-deficient and PTPN14-binding-deficient), primary keratinocyte lifespan assay, gene expression analysis bioRxiv : the preprint server for biologypreprint Medium 41890011

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Lipopolysaccharide transport and assembly at the outer membrane: the PEZ model. Nature reviews. Microbiology 291 27026255
2012 PTPN14 is required for the density-dependent control of YAP1. Genes & development 175 22948661
2012 PTPN14 interacts with and negatively regulates the oncogenic function of YAP. Oncogene 171 22525271
2017 A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer. Cancer cell 145 29017057
2015 MiR-21 promotes intrahepatic cholangiocarcinoma proliferation and growth in vitro and in vivo by targeting PTPN14 and PTEN. Oncotarget 99 25803229
2019 PTPN14 degradation by high-risk human papillomavirus E7 limits keratinocyte differentiation and contributes to HPV-mediated oncogenesis. Proceedings of the National Academy of Sciences of the United States of America 92 30894485
2016 High-Risk Human Papillomavirus E7 Proteins Target PTPN14 for Degradation. mBio 83 27651363
2012 Drosophila Pez acts in Hippo signaling to restrict intestinal stem cell proliferation. Current biology : CB 82 22305752
2013 The tyrosine phosphatase PTPN14 is a negative regulator of YAP activity. PloS one 80 23613971
2014 PTPN14 forms a complex with Kibra and LATS1 proteins and negatively regulates the YAP oncogenic function. The Journal of biological chemistry 78 25023289
2003 The protein tyrosine phosphatase Pez is a major phosphatase of adherens junctions and dephosphorylates beta-catenin. Molecular biology of the cell 78 12808048
2017 The PTPN14 Tumor Suppressor Is a Degradation Target of Human Papillomavirus E7. Journal of virology 71 28100625
2007 The protein tyrosine phosphatase Pez regulates TGFbeta, epithelial-mesenchymal transition, and organ development. The Journal of cell biology 71 17893246
2010 Protein tyrosine phosphatase PTPN14 is a regulator of lymphatic function and choanal development in humans. American journal of human genetics 70 20826270
2019 PTPN14 phosphatase and YAP promote TGFβ signalling in rheumatoid synoviocytes. Annals of the rheumatic diseases 56 30808624
2019 Structural basis for recognition of the tumor suppressor protein PTPN14 by the oncoprotein E7 of human papillomavirus. PLoS biology 52 31323018
2015 The tyrosine phosphatase PTPN14 (Pez) inhibits metastasis by altering protein trafficking. Science signaling 51 25690013
1995 Pez: a novel human cDNA encoding protein tyrosine phosphatase- and ezrin-like domains. Biochemical and biophysical research communications 50 7733990
2012 Mouse and human strategies identify PTPN14 as a modifier of angiogenesis and hereditary haemorrhagic telangiectasia. Nature communications 47 22233626
2000 Translocation of protein tyrosine phosphatase Pez/PTPD2/PTP36 to the nucleus is associated with induction of cell proliferation. Journal of cell science 42 10934049
2020 Exosomal CircPRRX1 Enhances Doxorubicin Resistance in Gastric Cancer by Regulating MiR-3064-5p/PTPN14 Signaling. Yonsei medical journal 34 32882759
2020 A Conserved Amino Acid in the C Terminus of Human Papillomavirus E7 Mediates Binding to PTPN14 and Repression of Epithelial Differentiation. Journal of virology 30 32581101
2016 The Regulatory Role of KIBRA and PTPN14 in Hippo Signaling and Beyond. Genes 30 27240404
2021 Loss-of-Function Variants in the Tumor-Suppressor Gene PTPN14 Confer Increased Cancer Risk. Cancer research 27 33602785
2017 MicroRNA-217 suppressed epithelial-to-mesenchymal transition in gastric cancer metastasis through targeting PTPN14. European review for medical and pharmacological sciences 22 28485805
2020 microRNA-217 suppressed epithelial-to-mesenchymal transition through targeting PTPN14 in gastric cancer. Bioscience reports 20 31793993
2020 PTPN14 aggravates inflammation through promoting proteasomal degradation of SOCS7 in acute liver failure. Cell death & disease 20 32978373
2023 A small molecule targeting the interaction between human papillomavirus E7 oncoprotein and cellular phosphatase PTPN14 exerts antitumoral activity in cervical cancer cells. Cancer letters 18 37532093
2022 A role for the NPM1/PTPN14/YAP axis in mediating hypoxia-induced chemoresistance to sorafenib in hepatocellular carcinoma. Cancer cell international 17 35135548
2020 Phospholipase D2 restores endothelial barrier function by promoting PTPN14-mediated VE-cadherin dephosphorylation. The Journal of biological chemistry 17 32327488
2021 Harmine alleviates atherogenesis by inhibiting disturbed flow-mediated endothelial activation via protein tyrosine phosphatase PTPN14 and YAP. British journal of pharmacology 16 33474722
2015 Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14. Frontiers in genetics 16 25815003
2023 PTPN14 promotes gastric cancer progression by PI3KA/AKT/mTOR pathway. Cell death & disease 15 36898991
2015 Suppressor of Deltex mediates Pez degradation and modulates Drosophila midgut homeostasis. Nature communications 15 25814387
2021 FAT1 and PTPN14 Regulate the Malignant Progression and Chemotherapy Resistance of Esophageal Cancer through the Hippo Signaling Pathway. Analytical cellular pathology (Amsterdam) 14 34712552
2024 mRNA-Lipid Nanoparticle-Mediated Restoration of PTPN14 Exhibits Antitumor Effects by Overcoming Anoikis Resistance in Triple-Negative Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 13 39189475
2008 PTP-Pez: a novel regulator of TGFbeta signaling. Cell cycle (Georgetown, Tex.) 13 18677119
2020 PTPN14 acts as a candidate tumor suppressor in prostate cancer and inhibits cell proliferation and invasion through modulating LATS1/YAP signaling. Molecular and cellular probes 12 32645410
2024 PTPN14 aggravates neointimal hyperplasia via boosting PDGFRβ signaling in smooth muscle cells. Nature communications 11 39191789
2024 HPV18 E7 inhibits LATS1 kinase and activates YAP1 by degrading PTPN14. mBio 11 39248565
2020 PTPN14, a target gene of miR-4295, restricts the growth and invasion of osteosarcoma cells through inactivation of YAP1 signalling. Clinical and experimental pharmacology & physiology 11 32141101
2023 MmuPV1 E7's interaction with PTPN14 delays Epithelial differentiation and contributes to virus-induced skin disease. PLoS pathogens 10 37036883
2018 PTPN14 regulates Roquin2 stability by tyrosine dephosphorylation. Cell cycle (Georgetown, Tex.) 10 30209976
2021 PTPN14 deficiency alleviates podocyte injury through suppressing inflammation and fibrosis by targeting TRIP6 in diabetic nephropathy. Biochemical and biophysical research communications 9 33684622
2022 The tyrosine phosphatase PTPN14 inhibits the activation of STAT3 in PEDV infected Vero cells. Veterinary microbiology 8 35259601
2020 PTPN21/Pez Is a Novel and Evolutionarily Conserved Key Regulator of Inflammation In Vivo. Current biology : CB 8 33296680
2019 Stathmin levels alter PTPN14 expression and impact neuroblastoma cell migration. British journal of cancer 8 31806880
2021 Recurrent PTPN14 Mutations in Trichilemmoma: Evidence for Distinct Pathways of Molecular Pathogenesis. The American Journal of dermatopathology 7 35830698
2001 Comparative analysis of the Band 4.1/ezrin-related protein tyrosine phosphatase Pez from two Drosophila species: implications for structure and function. Gene 7 11587846
2021 Association of mutation in PTPN14 gene and gingival fibromatosis with distinctive facies: a novel finding in whole exome sequencing. Clinical dysmorphology 3 33491997
2015 [Expression and clinical significance of PTPN14 in cholangiocarcinoma]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 3 26359106
2021 PTPN14 Mutations and Cervical Cancer. Cancer diagnosis & prognosis 2 35403138
2024 HPV18 E7 inhibits LATS1 kinase and activates YAP1 by degrading PTPN14. bioRxiv : the preprint server for biology 1 38496413
2026 Inactivation of the RB1 and PTPN14 tumor suppressors cooperatively enables the carcinogenic activity of the human papillomavirus E7 oncoprotein. bioRxiv : the preprint server for biology 0 41890011
2025 Analysis of knockout mice reveals critical female-specific roles for the Hippo pathway component PTPN14. Genes & development 0 40533389
2025 Fenofibrate-mediated inhibition of tumor proliferation and progression by modulating the PTPN14/MARK3/Hippo signaling axis. Pharmacological research 0 40858196
2025 Exosomal miRNA-148b/301a/423 cluster predicts pneumonitis risk in NSCLC with concurrent radiotherapy with immunotherapy via PTPN14-YAP signaling: a retrospective cohort study. Frontiers in immunology 0 41080561
2025 Oncogenic Role of PTPN14 in Pancreatic Cancer Through β-Catenin/NF-κB Pathway Activation. IUBMB life 0 41255096

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