Affinage

PTPN12

Tyrosine-protein phosphatase non-receptor type 12 · UniProt Q05209

Length
780 aa
Mass
88.1 kDa
Annotated
2026-06-10
88 papers in source corpus 47 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTPN12 (PTP-PEST) is a ubiquitously expressed, non-transmembrane cytosolic protein tyrosine phosphatase with an N-terminal catalytic domain and a C-terminal PEST-rich non-catalytic region that acts as a master suppressor of adhesion, cytoskeletal, and oncogenic receptor tyrosine kinase signaling (PMID:8454633, PMID:8887669). Its central physiological role is to dephosphorylate the focal-adhesion adaptor p130Cas—established as a selective substrate by substrate-trapping and confirmed by hyperphosphorylation in knockout fibroblasts and embryos—thereby restraining Cas–Crk complex formation, cell migration, and Rho GTPase output (PMID:8887669, PMID:9748319, PMID:9920935, PMID:17070019). Substrate engagement is achieved by a two-component mechanism in which the catalytic domain confers specificity while proline-rich motifs in the C-terminus dock onto SH3 and adaptor domains of partners, including the p130Cas SH3 domain, paxillin and Hic-5 LIM domains, PSTPIP/CD2BP1, filamin-A, and Csk (PMID:9285683, PMID:9497381, PMID:10092676, PMID:11711533, PMID:16973606, PMID:9287362). Through these scaffolds PTPN12 dephosphorylates a defined substrate set—paxillin, Pyk2, FAK at Tyr397, WASp, PSTPIP at Tyr344, p120 catenin at Tyr335, and the Rho regulators VAV2 and p190RhoGAP—to coordinately suppress Rac1 while sustaining RhoA, coupling membrane protrusion to tail retraction during migration and maintaining adherens-junction integrity (PMID:11711533, PMID:14707117, PMID:16317044, PMID:16513648, PMID:24284071, PMID:20519451). PTPN12 functions as a negative-feedback brake on oncogenic receptor tyrosine kinases, binding and dephosphorylating HER2, EGFR, MET, PDGFRβ, and TrkB, and its frequent inactivation drives triple-negative breast cancer and other tumors (PMID:21376233, PMID:23785422, PMID:29578538). Catalytic output is tuned by post-translational regulation: PKA/PKC phosphorylation at Ser39 lowers substrate affinity and governs migratory localization (PMID:7520867, PMID:36250939); an ERK–PIN1 axis acting on Ser571 (and Ser910 of FAK) promotes FAK Tyr397 dephosphorylation to enable Ras-driven invasion (PMID:19595712, PMID:21876001); ROS-induced oxidation inactivates the enzyme, while SRXN1-mediated desulfinylation at Cys164 restores activity and stability to permit NLRP3 dephosphorylation and suppression of liver fibrosis (PMID:30297534, PMID:39446334). PTPN12 is essential for embryonic vascular and developmental viability and additionally targets ABL1, VCP/p97, and AMPK in contexts of renal cancer, glioblastoma invasion, and hypoxia-induced angiogenesis (PMID:17070019, PMID:23105101, PMID:30297534, PMID:29743287, PMID:33323505). Disease-linked loss of partner binding—PSTPIP1 mutations in PAPA syndrome and filamin-A mutations in mitral valve prolapse—disrupts PTPN12 recruitment and downstream substrate regulation (PMID:11971877, PMID:26594644).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1993 High

    Established PTPN12 as a bona fide cytosolic tyrosine-specific phosphatase, defining its enzymatic identity and domain architecture.

    Evidence recombinant GST-fusion protein with in vitro phosphatase assays against phosphotyrosine substrates

    PMID:8454633

    Open questions at the time
    • No physiological substrate identified
    • No cellular localization or partner mapping
  2. 1994 High

    Revealed that PTPN12 catalytic activity is not constitutive but is dialed down by serine phosphorylation, introducing the concept of upstream signaling control of the phosphatase.

    Evidence in vitro PKA/PKC kinase assays, Ser39/Ser435 site mapping, activity assays on enzyme from TPA-treated HeLa cells

    PMID:7520867

    Open questions at the time
    • Functional consequence of Ser39 phosphorylation for cell behavior not yet shown
    • Did not identify physiological substrates affected
  3. 1996 High

    Identified p130Cas as the first selective physiological substrate, anchoring PTPN12 in adhesion signaling.

    Evidence substrate-trapping catalytic-dead mutants, Co-IP across multiple cell lines, in vitro dephosphorylation

    PMID:8887669

    Open questions at the time
    • Mechanism of substrate selectivity unresolved
    • No functional/cellular phenotype demonstrated
  4. 1997 High

    Defined a two-component substrate-recognition mechanism—catalytic specificity plus a proline-rich/SH3 docking interaction—explaining how PTPN12 achieves substrate selectivity.

    Evidence proline-rich motif mutagenesis (P337A), in vitro binding and dephosphorylation assays; Csk SH3 association mapping

    PMID:9285683 PMID:9287362

    Open questions at the time
    • Generality of docking mechanism across substrates not yet established
    • Csk-PTP-PEST functional output undefined
  5. 1998 High

    Showed PTPN12 docks onto focal-adhesion scaffolds (paxillin, indirectly FAK) and confirmed p130Cas as a physiological substrate genetically, linking the phosphatase to adhesion complexes.

    Evidence in vitro binding, Co-IP, and PTP-PEST-null fibroblasts showing p130Cas hyperphosphorylation; Cas-family SH3 binding

    PMID:9497381 PMID:9748319

    Open questions at the time
    • Identity of the 180/97 kDa hyperphosphorylated proteins not resolved at the time
    • Functional migration consequence not yet tested
  6. 1999 High

    Demonstrated that PTPN12 regulates cell migration through p130Cas dephosphorylation, converting a biochemical activity into a defined cellular function.

    Evidence PTP-PEST-overexpressing Rat1 fibroblasts, migration/spreading assays, Cas-Crk Co-IP, leading-edge redistribution; B-cell scaffold analysis with Shc/Pyk2/FAK/Cas

    PMID:11432829 PMID:9920935

    Open questions at the time
    • Rho GTPase link not yet mechanistically defined
    • Direct vs scaffold-mediated dephosphorylation of FAK/Pyk2 unresolved
  7. 2002 High

    Connected PTPN12 to Rho GTPase regulation, showing it suppresses Rac1 to control protrusion and motility, and linked partner disruption (PSTPIP1) to autoinflammatory PAPA syndrome.

    Evidence PTP-PEST-null fibroblasts, catalytic-dead overexpression, Rac1 pulldown assays with constitutively-active Rac1 rescue; yeast two-hybrid with PAPA disease mutants

    PMID:11971877 PMID:12376562

    Open questions at the time
    • Direct Rho GTPase regulatory substrates not yet identified in 2002
    • How Rac1 suppression integrates with RhoA unknown
  8. 2001 High

    Identified PSTPIP/CD2BP1 as a substrate and adaptor that scaffolds PTPN12 to WASp, extending the phosphatase into actin-regulatory and immune signaling.

    Evidence domain-mapped Co-IP, tryptic phosphopeptide mapping of PSTPIP Tyr344, substrate-trapping; WASp Tyr291 dephosphorylation in T cells using knockout/transgene/Fyn-/- models

    PMID:11711533 PMID:14707117

    Open questions at the time
    • In vivo immune consequences of WASp regulation not fully delineated at the time
    • Quantitative contribution of scaffold vs direct catalysis unclear
  9. 2006 High

    Established that PTPN12 coordinately tunes Rac1 and RhoA by directly dephosphorylating the upstream GEF VAV2 and GAP p190RhoGAP, and is essential for embryonic development.

    Evidence PTP-PEST-null fibroblasts, direct dephosphorylation assays, Rho GTPase readouts; knockout mouse embryo phenotyping with p130Cas hyperphosphorylation; filamin-A binding and cytokinesis assays

    PMID:16513648 PMID:16973606 PMID:17070019

    Open questions at the time
    • Tissue-specific developmental requirements not yet dissected
    • Filamin-A scaffold role in cytokinesis mechanistically incomplete
  10. 2009 High

    Defined the ERK–PIN1–FAK regulatory axis through which Ras transformation co-opts PTPN12 to dephosphorylate FAK Tyr397 and promote migration and metastasis.

    Evidence kinase inhibitors, Co-IP, in vitro dephosphorylation/isomerization, migration/invasion and xenograft metastasis models; follow-up mapping PTP-PEST Ser571/PIN1

    PMID:19595712 PMID:21876001

    Open questions at the time
    • Context dependence of FAK dephosphorylation (pro- vs anti-migratory) not fully reconciled
    • Structural basis of PIN1-induced FAK binding undefined
  11. 2011 High

    Identified PTPN12 as a tumor suppressor that restrains multiple oncogenic RTKs (HER2, EGFR, TrkB), establishing its loss as a driver of malignancy.

    Evidence genetic RNAi screen, PTPN12-RTK Co-IP, RTK phosphorylation assays, restoration rescue in TNBC cells, xenografts; neuronal TrkB knockdown screen

    PMID:21376233 PMID:23785422

    Open questions at the time
    • Direct vs indirect RTK dephosphorylation not all resolved in 2011
    • Which RTK is rate-limiting in given tumors unclear
  12. 2013 High

    Demonstrated PTPN12's broad requirement across immune and epithelial cells—T cell secondary responses, DC and macrophage migration/fusion, adherens junctions—converging on Pyk2/paxillin and p120-catenin Tyr335 dephosphorylation.

    Evidence conditional knockouts in T cells/DCs/macrophages with Pyk2 inhibitor epistasis; substrate-trapping and Y335F mutagenesis of p120 catenin; calcium-switch and Rho GTPase assays

    PMID:20519451 PMID:20727793 PMID:23589331 PMID:24284071 PMID:24366546

    Open questions at the time
    • How a single phosphatase achieves cell-type-specific substrate prioritization unclear
    • Integration of multiple substrate axes in vivo not fully resolved
  13. 2012 High

    Confirmed the endothelial and vascular requirement for PTPN12, tying loss to hyperphosphorylation of Cas, paxillin, and Pyk2 and to vascular development in vivo.

    Evidence inducible endothelial-specific knockout mice, primary EC adhesion/migration assays, phosphotyrosine immunoblotting; osteoclast dynamin-Pyk2 cooperative dephosphorylation

    PMID:22342188 PMID:23105101

    Open questions at the time
    • Upstream signals targeting PTPN12 to nascent vessels unknown
    • Dynamin GTPase requirement for Pyk2 dephosphorylation mechanistically incomplete
  14. 2015 High

    Extended PTPN12's tumor-suppressive function to in vivo ErbB2 breast cancer and linked partner-disrupting filamin-A mutations to mitral valve prolapse via impaired Src/p190RhoGAP regulation.

    Evidence conditional knockout in ErbB2 mammary model with Pyk2 inhibitor rescue; FlnA MVP-mutant yeast two-hybrid/pulldown/Co-IP and substrate activity assays; EphA3 caspase-cleavage fragment analysis

    PMID:26391955 PMID:26594644 PMID:26644181

    Open questions at the time
    • Why ErbB2 phosphorylation is unchanged while adhesion substrates rise is unresolved
    • EphA3-cleavage fragment regulation requires further mechanistic validation
  15. 2018 High

    Revealed PTPN12 as a redox- and complex-regulated hub controlling RTK negative feedback (MET/PDGFRβ/EGFR), Cas–VCP stability in glioblastoma invasion, and ABL1 inactivation under oxidative stress in renal cancer.

    Evidence systematic substrate-trapping and Co-IP with RTKs plus combined-inhibitor PDX models; PTP-PEST-Cas-Vcp Co-IP with Vcp Y805 mutagenesis and GBM models; q-oxPTPome profiling and substrate-trapping for ABL1

    PMID:29578538 PMID:29743287 PMID:30297534

    Open questions at the time
    • Site-specificity of multi-RTK dephosphorylation not fully mapped
    • Reversibility of ROS-driven oxidation in vivo not quantified
  16. 2020 High

    Identified AMPK as a substrate, placing PTPN12 in hypoxia-induced AMPK activation, endothelial autophagy, and angiogenesis.

    Evidence IP-MS, domain-specific Co-IP of AMPKα subunits with PTP-PEST catalytic domain, knockdown with metformin/rapamycin rescue, tube-formation assays

    PMID:33323505

    Open questions at the time
    • Exact AMPK tyrosine dephosphorylation site not experimentally pinpointed
    • Coupling between tyrosine dephosphorylation and Thr172 activation unresolved
  17. 2024 High

    Defined a redox-controlled SRXN1–PTPN12–NLRP3 axis in which desulfinylation at Cys164 restores phosphatase activity to dephosphorylate NLRP3 and suppress liver fibrosis.

    Evidence HSC-specific Srxn1 knockout mice, PTPN12 C164A sulfinylation-resistant mutant, NLRP3 tyrosine phosphorylation and fibrosis models; preprint Abl-Ptpn12-p130Cas epistasis in lens

    PMID:39446334 PMID:bio_10.1101_2024.10.24.619064

    Open questions at the time
    • Generality of NLRP3 regulation beyond hepatic stellate cells unknown
    • Interplay between Cys164 sulfinylation and other PTMs not integrated
  18. 2023 Low

    Began structural rationalization of how tyrosine phosphorylation at interface residues (Tyr64/Tyr88) and Ser39 status tune catalytic-loop dynamics and substrate affinity.

    Evidence MD simulations and phosphomimetic Co-IP for Tyr64/AMPKα2; S39A/CS mutant rescue in PTP-PEST-null MEFs with migration/adhesion/localization assays

    PMID:36250939 PMID:36645312 PMID:39423851

    Open questions at the time
    • Tyr64/Tyr88 phosphorylation predictions await direct structural determination
    • Predicted AMPK Tyr232 dephosphorylation site not experimentally validated
    • Computational models not orthogonally confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single phosphatase selects among its many substrates and RTKs in a given cell type, and how its layered PTM code (Ser39, Ser571, Tyr64, Cys164 oxidation/desulfinylation) is integrated in real time, remains unresolved.
  • No high-resolution structure of full-length PTPN12 with substrate
  • Quantitative substrate hierarchy across cell types undefined
  • Spatiotemporal coordination of competing PTMs unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0098772 molecular function regulator activity 4 GO:0016787 hydrolase activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005856 cytoskeleton 4 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-168256 Immune System 6 R-HSA-1643685 Disease 5 R-HSA-1474244 Extracellular matrix organization 4 R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 2
Partners
BCAR1CSKFLNAPSTPIP1PTK2BPXNVCPWAS

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 PTP-PEST is a non-transmembrane cytosolic protein tyrosine phosphatase with an N-terminal catalytic domain and a C-terminal PEST-rich non-catalytic segment; recombinant protein expressed in E. coli demonstrated intrinsic phosphatase activity against phosphotyrosine-containing substrates including the autophosphorylated insulin receptor kinase domain, but did not dephosphorylate phosphoserine substrates. Recombinant expression (GST-fusion in E. coli), in vitro phosphatase activity assays The Journal of Biological Chemistry High 8454633
1994 PTP-PEST is regulated by serine phosphorylation: PKA and PKC phosphorylate PTP-PEST at Ser39 and Ser435 in vitro and in intact HeLa cells treated with TPA, forskolin, or IBMX. Phosphorylation at Ser39 reduces PTP-PEST catalytic activity by decreasing substrate affinity, and immunoprecipitated PTP-PEST from TPA-treated cells showed significantly lower phosphatase activity. Recombinant baculovirus expression, in vitro kinase assays (PKA, PKC), site identification, activity assays on immunoprecipitated enzyme from TPA-treated HeLa cells The EMBO Journal High 7520867
1996 p130Cas is a major, selective substrate of PTP-PEST: substrate-trapping catalytically inactive mutants of PTP-PEST formed stable complexes exclusively with p130Cas in HeLa cell lysates and multiple cell lines, and wild-type PTP-PEST preferentially dephosphorylated p130Cas in vitro. This selectivity was not observed with other PTP family members. Substrate-trapping mutagenesis (catalytic-dead mutant), co-immunoprecipitation, in vitro dephosphorylation assays, immunoblotting Molecular and Cellular Biology High 8887669
1997 PTP-PEST recognizes p130Cas as a substrate via two distinct mechanisms: the catalytic domain contributes specificity, while a proline-rich sequence (P335PPKPPR) in the PTP-PEST C-terminus binds the SH3 domain of p130Cas with high affinity. Mutation of Pro337 to alanine significantly impaired p130Cas dephosphorylation without abolishing SH3-mediated association, establishing SH3-proline-rich interaction as a novel substrate-recognition mechanism that increases dephosphorylation efficiency. Mutagenesis of proline-rich motif, in vitro binding assays, dephosphorylation assays Oncogene High 9285683
1997 PTP-PEST associates with Csk (p50csk) in both hemopoietic and non-hemopoietic cells via the SH3 domain of Csk and a proline-rich region (PPPLPERTPESFVLADM) in PTP-PEST outside its catalytic domain. PTP-PEST, unlike PEP, also complexes with the adaptor Shc in the same cells, suggesting distinct functional contexts for Csk-PTP-PEST vs Csk-PEP complexes. Co-immunoprecipitation, domain-mapping pulldown assays, cell fractionation The Journal of Biological Chemistry Medium 9287362
1998 PTP-PEST directly binds paxillin through its C-terminal non-catalytic domain; this interaction was detected in vitro and the complex co-immunoprecipitates with both FAK and paxillin from chicken embryo cell lysates. The FAK–PTP-PEST association is indirect, mediated through paxillin. In vitro binding with recombinant proteins, co-immunoprecipitation from cell lysates The Journal of Biological Chemistry High 9497381
1998 Gene-targeted PTP-PEST-null fibroblasts display constitutive hyperphosphorylation of p130Cas (as well as 180 and 97 kDa proteins), confirming p130Cas as a physiological substrate. PTP-PEST also interacts via its proline-rich sequence (332PPKPPR337) with SH3 domains of other Cas family members Hef1 and Sin in vitro, indicating it may be a general Cas-family modulator. Gene targeting (PTP-PEST knockout MEFs), substrate-trapping, immunoprecipitation, in vitro SH3-binding assays Biochemistry High 9748319
1999 Overexpression of PTP-PEST in Rat1 fibroblasts reduces p130Cas tyrosine phosphorylation, decreases p130Cas–Crk association, impairs redistribution of p130Cas to the leading edge, and markedly reduces cell migration rate without affecting initial cell attachment/spreading or MAPK activation after integrin engagement. These data establish PTP-PEST as a regulator of cell migration acting through p130Cas dephosphorylation. Stable cell lines overexpressing PTP-PEST, phosphotyrosine immunoblotting, co-immunoprecipitation (Cas-Crk), cell migration assays (haptotaxis, wound healing), MAPK activation assays The Journal of Biological Chemistry High 9920935
1999 Hic-5 (a paxillin homologue) directly binds PTP-PEST in mammalian cells; yeast two-hybrid and in vitro binding experiments mapped the binding to the LIM3 domain of Hic-5 and the second proline-rich region (Pro-2) of PTP-PEST — the same PTP-PEST region that also binds paxillin. Yeast two-hybrid, in vitro binding with deletion/point mutants, co-immunoprecipitation The Journal of Biological Chemistry Medium 10092676
2001 PTP-PEST functions as a scaffold phosphatase negatively regulating lymphocyte activation: it is constitutively associated with Shc, paxillin, Csk, and Cas in B cells; PTP-PEST induces dephosphorylation of Shc, Pyk2, FAK, and Cas and inactivates the Ras pathway. Overexpression suppresses and antisense increases lymphocyte activation, and Shc–PTP-PEST association is augmented by antigen receptor stimulation. Overexpression, antisense knockdown, co-immunoprecipitation, phosphotyrosine immunoblotting, structure-function analysis The EMBO Journal High 11432829
2001 PSTPIP (CD2BP1) is a substrate of PTP-PEST: they interact directly through the CTH domain of PTP-PEST and the coiled-coil domain of PSTPIP; PTP-PEST dephosphorylates PSTPIP at Tyr344 (identified by tryptic phosphopeptide mapping). PSTPIP acts as a scaffold between PTP-PEST and WASp, enabling PTP-PEST to dephosphorylate WASp. EGF and PDGF receptor activation induces PSTPIP phosphorylation via c-Abl (not Src). In vivo co-immunoprecipitation, domain-mapping, tryptic phosphopeptide mapping, in vitro dephosphorylation, inhibitor (PP2) studies, substrate-trapping The Journal of Biological Chemistry High 11711533
2002 PAPA syndrome-causing mutations E250Q and A230T in CD2BP1 (PSTPIP1/CD2BP1) severely reduce binding to PTP-PEST as demonstrated by yeast two-hybrid assays, linking disrupted PTP-PEST–PSTPIP interaction to an autoinflammatory disorder. Yeast two-hybrid binding assays with disease-mutant CD2BP1 proteins Human Molecular Genetics Medium 11971877
2002 PTP-PEST controls cell motility by suppressing Rac1 activity: overexpression of catalytically active (but not inactive) PTP-PEST impairs haptotaxis, cell spreading, membrane protrusion, and membrane ruffling, and suppresses integrin- and growth-factor-stimulated Rac1 activation. PTP-PEST-null fibroblasts have enhanced Rac1 activity, and co-expression of constitutively active Rac1 rescues PTP-PEST-induced migration inhibition. Overexpression (WT and catalytic-dead), PTP-PEST null fibroblasts, Rac1 activity assays (GST-PAK pulldown), haptotaxis and spreading assays, PDGF stimulation Journal of Cell Science High 12376562
2003 Nitric oxide (NO) decreases aortic smooth muscle cell motility via a cGMP-dependent mechanism that increases PTP-PEST activity, leading to dephosphorylation of p130Cas and dissociation of the Cas–Crk complex. Dominant-negative PTP-PEST blocks NO-induced p130Cas dephosphorylation and antimotogenesis; overexpression of PTP-PEST mimics NO effects. NO donor treatments, cGMP analog/guanylyl cyclase inhibitor pharmacology, dominant-negative and overexpression constructs, phosphotyrosine immunoblotting, Cas–Crk co-immunoprecipitation, cell migration assays American Journal of Physiology. Heart and Circulatory Physiology Medium 12714323
2004 PTP-PEST dephosphorylates WASp and inhibits WASp-driven actin polymerization and immunological synapse formation in T cells. This occurs via PSTPIP1-mediated scaffolding: PTP-PEST interacts with WASp through PSTPIP1. TCR-induced WASp phosphorylation at Tyr291 (by Fyn) is required for WASp effector function; PTP-PEST counteracts Fyn-mediated phosphorylation. WASp knockout mice with transgene complementation, site-directed mutagenesis (Y291F), Fyn-/- T cells, co-localization, co-immunoprecipitation, actin polymerization assays, synapse formation assays, NFAT reporter assays The Journal of Experimental Medicine High 14707117
2005 Paxillin is essential for PTP-PEST-mediated inhibition of cell spreading and Rac1 activation, and for PTP-PEST stimulation of cell migration. PTP-PEST function involves binding to paxillin C-terminal LIM domains and signaling through paxillin Tyr31/118 and the LD4 motif. PKL/GIT2 (an ARF-GAP paxillin LD4-binding partner) is identified as a PTP-PEST substrate by substrate-trapping and immunoprecipitation. PTP-PEST-/- and paxillin-/- fibroblasts, substrate-trapping, co-immunoprecipitation, mutagenesis (paxillin LIM, Tyr31/118, LD4), Rac1 activity assays, cell spreading/migration assays Journal of Cell Science High 16317044
2006 PTP-PEST couples leading-edge membrane protrusion to tail retraction during cell migration by directly targeting the upstream Rho GTPase regulators VAV2 (a Rac1 GEF) and p190RhoGAP (a RhoA GAP). PTP-PEST null fibroblasts show enhanced Rac1 and decreased RhoA activity with exaggerated protrusions and unretracted tails. PTP-PEST directly dephosphorylates VAV2 and p190RhoGAP, which regulates their activities. PTP-PEST null fibroblasts, Rho GTPase activity assays, direct dephosphorylation assays, integrin-mediated adhesion stimulation The Journal of Biological Chemistry High 16513648
2006 Filamin-A is a novel binding partner of PTP-PEST; the interaction was mapped to the fourth proline-rich region (Pro4) of PTP-PEST. PTP-PEST overexpression in HeLa cells causes multinucleated cell formation (cytokinesis defect), and a PTP-PEST mutant lacking Pro4 that cannot bind filamin-A fails to induce this phenotype. Depletion of filamin-A also reduces PTP-PEST-dependent multinucleation. Proteomics (GST-pulldown + mass spectrometry), co-immunoprecipitation, domain-mapping, overexpression/mutant rescue, filamin-A siRNA depletion The Journal of Biological Chemistry High 16973606
2006 PTP-PEST is essential for early embryonic development; PTP-PEST-null embryos display defects in embryo turning, somitogenesis, vasculogenesis, liver development, and neuroepithelium integrity, leading to lethality at E9.5–10.5. Increased p130Cas tyrosine phosphorylation is the earliest detected biochemical defect in PTP-PEST-/- embryos (E9.5). Gene targeting (PTP-PEST-/- mice), embryo morphological analysis, phosphotyrosine immunoblotting for p130Cas Mechanisms of Development High 17070019
2006 CD2BP1 (PSTPIP1) acts as a scaffold linking PTP-PEST to the CD2 signalsome; disruption of PTP-PEST–CD2BP1 association rescues T cells from CD2BP1-mediated inhibition of T cell activation. CD2BP1 overexpression selectively attenuates PLCγ1, ERK1/2, and p38 phosphorylation in a PTP-PEST-dependent manner. Primary T cell transduction, mutagenesis of PTP-PEST–CD2BP1 interaction interface, cytokine/signaling reporter assays (CD69, IL-2, IFN-γ), immunoblotting Journal of Immunology Medium 16670297
2009 Activated Ras induces FAK Tyr397 dephosphorylation via a Fgd1-Cdc42-PAK1-MEK-ERK signaling cascade: ERK phosphorylates FAK at Ser910, which recruits PIN1 and PTP-PEST to colocalize with FAK at lamellipodia. PIN1 prolyl-isomerization of phospho-Ser910 FAK promotes PTP-PEST binding to and dephosphorylation of FAK Tyr397, thereby promoting Ras-induced cell migration and metastasis. Signaling pathway analysis, kinase inhibitors, co-immunoprecipitation, in vitro dephosphorylation/isomerization assays, cell migration/invasion assays, xenograft metastasis models Molecular Cell High 19595712
2010 PTP-PEST promotes secondary T cell responses by specifically dephosphorylating Pyk2 (a substrate of Fyn kinase). Conditional deletion of PTP-PEST in T cells impairs secondary responses, anergy prevention, and autoimmunity induction but not primary responses or T cell development. PTP-PEST also promotes formation of T cell homoaggregates that enhance T cell activation. Conditional Ptpn12 knockout mice (T cell-specific), secondary antigen challenge, Pyk2 phosphorylation analysis, T cell aggregate formation assays Immunity High 20727793
2010 PTP-PEST regulates adherens junction integrity and epithelial cell motility in colon carcinoma cells by controlling Rho GTPase activity. PTP-PEST knockdown enhances migration, disrupts adherens junction assembly after calcium switch, increases Rac1 activity, and decreases RhoA activity in response to cadherin engagement, without altering E-cadherin expression. PTP-PEST localizes to adherens junctions. siRNA/shRNA knockdown, ectopic overexpression, calcium switch assay, Rho GTPase activity assays, cell migration assays (haptotaxis/chemotaxis), immunofluorescence localization American Journal of Physiology. Cell Physiology Medium 20519451
2011 Activated Ras induces ERK1/2-dependent phosphorylation of PTP-PEST at Ser571, which recruits PIN1 to bind PTP-PEST. PIN1 isomerization of phospho-Ser571 PTP-PEST increases the PTP-PEST–FAK interaction, leading to dephosphorylation of FAK Tyr397 and promotion of migration, invasion, and metastasis in Ras-transformed cells. Site-directed mutagenesis (S571A), co-immunoprecipitation, in vitro dephosphorylation assays, cell migration/invasion assays, xenograft metastasis models Molecular and Cellular Biology High 21876001
2011 PTPN12 suppresses triple-negative breast cancer transformation by interacting with and inhibiting multiple oncogenic receptor tyrosine kinases including HER2 and EGFR. PTPN12 is frequently inactivated in TNBCs, and restoration of PTPN12 impairs tumorigenic and metastatic potential of PTPN12-deficient TNBC cells. Genetic RNAi screen, co-immunoprecipitation (PTPN12 with RTKs), RTK phosphorylation assays, overexpression rescue in TNBC cells, xenograft tumor models Cell High 21376233
2011 PTPN12 is a negative regulator of TrkB tyrosine phosphorylation and downstream ERK1/2 activation in neuronal cells. Endogenous PTPN12 also negatively regulates phosphorylation of p130Cas and FAK in the context of BDNF-TrkB signaling and neurite outgrowth. RNAi-based phosphatase loss-of-function screen (254 phosphatases), PTPN12 knockdown validation, TrkB/ERK/p130Cas/FAK phosphorylation assays, neurite outgrowth assays PloS One Medium 23785422
2012 PTP-PEST is required for integrin-mediated adhesion and migration of endothelial cells; its loss leads to hyperphosphorylation of Cas, paxillin, and Pyk2. PTP-PEST expression in endothelial cells is required for normal vascular development and embryonic viability in vivo, but is not needed for endothelial cell differentiation, proliferation, or permeability control. Inducible endothelial-specific PTP-PEST knockout mice, primary endothelial cell cultures, adhesion/migration assays, phosphotyrosine immunoblotting, conditional in vivo vascular phenotyping The Journal of Biological Chemistry High 23105101
2012 Dynamin and PTP-PEST cooperatively regulate Pyk2 dephosphorylation at Tyr402 in osteoclasts; the mechanism involves binding of Pyk2's FERM domain to dynamin's PH domain, and dynamin GTPase activity is required. PTP-PEST mediates the actual dephosphorylation step. Co-immunoprecipitation (Pyk2-dynamin), domain-mapping, GTPase-deficient dynamin mutants, in vitro dephosphorylation assays The International Journal of Biochemistry & Cell Biology Medium 22342188
2013 PTPN12 protects cells against ROS-induced apoptosis by supporting FOXO1/3a activation (required for antioxidant gene upregulation); this function is mediated through suppression of PDK1, which is hyperstimulated in PTPN12-deficient cells. PTPN12-deficient MEFs show increased ROS-induced apoptosis under antioxidant-depleted conditions. PTPN12-deficient MEFs, ROS/apoptosis assays, FOXO1/3a activation assays, PDK1 activity analysis Oncogene Medium 23435421
2013 PTP-PEST dephosphorylates p120 catenin at Tyr335 in epithelial cells (identified by substrate-trapping and point mutagenesis). PTP-PEST knockdown increases cytosolic p120, enhances p120 association with VAV2 and cortactin, activates VAV2 exchange activity, and promotes Rac1 activation with corresponding decreases in RhoA activity. A Y335F p120 mutant fails to show these effects, linking the specific dephosphorylation site to Rho GTPase regulation and cell motility. Substrate-trapping, shRNA knockdown, site-directed mutagenesis (p120 Y335F), co-immunoprecipitation, Rho GTPase activity assays, VAV2 GEF assays, cell migration assays Journal of Cell Science High 24284071
2013 PTP-PEST is required for macrophage fusion into multinucleated giant cells (IL-4-induced) and osteoclasts (RANKL-induced); it is needed for CCL2-induced macrophage migration, macrophage polarization, and integrin-induced spreading. Mechanistically, PTP-PEST loss causes hyperphosphorylation of Pyk2 and paxillin, and pharmacological Pyk2 inhibition in normal macrophages recapitulates the fusion defect. Macrophage-targeted conditional PTP-PEST knockout, in vitro fusion assays, foreign body implantation in vivo, Pyk2/paxillin phosphorylation analysis, Pyk2 inhibitor rescue Molecular and Cellular Biology High 23589331
2013 PTPN12 is required for DC migration from peripheral tissues to secondary lymphoid organs, thereby enabling T cell-dependent immune responses. Loss of PTPN12 in DCs results in hyperphosphorylation of Pyk2 and its substrate paxillin. Pharmacological inhibition or knockdown of Pyk2 also impairs DC migration, establishing Pyk2 deregulation as the key mechanism underlying the migration defect. DC-specific conditional PTPN12 knockout, in vivo DC migration assays, Pyk2/paxillin phosphorylation analysis, Pyk2 inhibitor and siRNA experiments, T cell immune response assays Molecular and Cellular Biology High 24366546
2013 SKAP-Hom (Src kinase-associated phosphoprotein 55 homologue) is a novel substrate of PTP-PEST identified by modified yeast substrate-trapping two-hybrid. In vitro pulldown confirmed that the PTP-PEST catalytic domain binds SKAP-Hom Tyr260/Tyr297, and the PTP-PEST Pro1 domain binds the SKAP-Hom SH3 domain. SKAP-Hom deficiency impairs cell migration, and the SH3 domain mutant (which cannot recruit PTP-PEST) shows enhanced migration with elevated SKAP-Hom tyrosine phosphorylation. Yeast substrate-trapping two-hybrid, in vitro pulldown with domain mutants, SKAP-Hom-deficient MEF rescue experiments (WT, Y260F, Y260F/Y297F, W335K mutants), wound-healing and transwell migration assays The Journal of Biological Chemistry Medium 23897807
2015 PTPN12 deficiency in a mouse ErbB2-dependent breast cancer model accelerates tumor development and lung metastases. PTPN12-deficient breast cancer cells show increased tyrosine phosphorylation of Cas, paxillin, and Pyk2 (but no detectable increase in ErbB2 phosphorylation), enhanced anoikis resistance, augmented migration and invasion, and partial EMT features. Pyk2 inhibition corrects enhanced migration. Conditional PTPN12 knockout in ErbB2 mouse mammary tumor model, in vivo tumor/metastasis analysis, Pyk2/Cas/paxillin phosphorylation immunoblotting, anoikis assays, migration/invasion assays, Pyk2 inhibitor rescue Molecular and Cellular Biology High 26391955
2015 MVP-associated filamin A (FlnA) mutations (G288R, P637Q, H743P) abolish FlnA/PTPN12 interaction as shown by yeast two-hybrid, pulldown, and co-immunoprecipitation. These mutations impair activation of two PTPN12 substrates, Src and p190RhoGAP, suggesting that loss of FlnA–PTPN12 interaction underlies the pathophysiology of FlnA-associated mitral valve prolapse. Yeast two-hybrid (first repeats 1–8 of FlnA as bait), pulldown assays, co-immunoprecipitation, Src and p190RhoGAP activity assays with MVP mutants Journal of Cardiovascular Development and Disease Medium 26594644
2015 PTP-PEST controls EphA3 receptor activation: ephrinA5 stimulation triggers caspase-3-mediated cleavage generating a catalytically active N-terminal fragment of PTP-PEST that attenuates EphA3 phosphorylation and internalisation. This fragment is recruited to EphA3 signaling clusters within plasma membrane. Modulation of actin polymerization affects EphA3 phosphorylation similarly to PTP-PEST overexpression, indicating dual regulation through direct phosphatase activity and cytoskeletal remodeling. Cell fractionation (detergent-free plasma membrane fragments), overexpression and dominant-negative actin approaches, EphA3 phosphorylation assays, EphA3 internalization assays, caspase-3 cleavage analysis Journal of Cell Science Medium 26644181
2018 PTP-PEST physically bridges the focal adhesion protein Cas and the ATP-dependent ubiquitin segregase Vcp (p97/VCP); both Cas and Vcp are PTP-PEST substrates. Phosphorylation of Vcp Tyr805 controls its affinity for Cas in focal adhesions, regulating ubiquitination and protein stability of Cas. Perturbing PTP-PEST-mediated phosphorylation of Cas and Vcp alters GBM cell invasive growth in vitro and in vivo. Co-immunoprecipitation (PTP-PEST–Cas–Vcp complex), substrate-trapping, Vcp Y805 mutagenesis, ubiquitination assays, GBM invasion assays in vitro and mouse models Cancer Research High 29743287
2018 PTPN12 is recruited to and dephosphorylates MET, PDGFRβ, and EGFR after ligand stimulation, serving as a negative feedback mechanism to limit RTK signaling. Cancer-associated PTPN12 mutations or reduced PTPN12 levels diminish this feedback, leading to aberrant activity of these RTKs. Combined inhibition of PDGFRβ and MET (receptors co-regulated by PTPN12) induces apoptosis in PTPN12-deficient TNBC cells in vitro and regression in vivo. Systematic substrate identification (PTPN12 substrate-trapping), co-immunoprecipitation (PTPN12–RTK complexes), RTK phosphorylation assays, PTPN12 restoration experiments, combined RTK inhibitor in vitro/in vivo assays including patient-derived xenografts Nature Medicine High 29578538
2018 PTPN12 oxidation (by elevated ROS due to FH deficiency) is the mechanism of ABL1 phosphatase inactivation in HLRCC-associated papillary renal cell carcinoma. Using quantitative oxPTPome profiling, PTPN12 was found to be among the most oxidized PTPs; substrate-trapping showed only PTPN12 (not other oxidized PTPs) could target ABL1. PTPN12 knockdown confirmed it is the major ABL1 phosphatase; PTPN12 overexpression inhibited ABL1 phosphorylation and cancer cell growth. Quantitative oxidized-PTPome profiling (q-oxPTPome), substrate-trapping mutants, PTPN12 knockdown, PTPN12 overexpression, ABL1 phosphorylation assays Cancer Research High 30297534
2020 PTP-PEST promotes hypoxia-induced AMPK activation and endothelial autophagy/angiogenesis. Under normoxia, AMPK α subunits (α1 and α2) interact with the catalytic domain of PTP-PEST (confirmed by Co-IP); under hypoxia this interaction is lost. PTP-PEST knockdown abrogates hypoxia-induced tyrosine dephosphorylation and Thr172 phosphorylation (activation) of AMPK, and blocks autophagy (LC3 degradation) and angiogenesis. AMPK activator (metformin) rescues the autophagy defect; autophagy inducer (rapamycin) rescues angiogenesis. Co-immunoprecipitation (AMPK α subunits with PTP-PEST catalytic domain), immunoprecipitation + mass spectrometry, PTPN12 knockdown, hypoxia experiments, AMPK activation assays (Thr172/tyrosine phosphorylation), LC3 autophagy assays, tube formation and migration assays, pharmacological rescue (metformin, rapamycin) Journal of Cell Science High 33323505
2021 GB1e (an oncogenic isoform of GABAB1) promotes EGFR signaling by interacting with PTPN12 and disrupting the EGFR–PTPN12 interaction, thereby preventing PTPN12-mediated EGFR dephosphorylation. Phosphorylation of GB1e at Tyr230 and Tyr404 is required for this disruption. Co-immunoprecipitation (GB1e–PTPN12, EGFR–PTPN12), site-directed mutagenesis (GB1e Y230/Y404), EGFR phosphorylation assays, in vitro and in vivo breast cancer cell assays iScience Medium 34778730
2023 Phosphorylation/dephosphorylation of PTP-PEST at Ser39 is critical for cell migration: constitutively active (S39A) PTP-PEST causes decreased cell migration despite enhanced phosphatase activity, while WT and kinase-dead (CS) PTP-PEST support normal or reduced migration respectively. Ser39-phosphorylated PTP-PEST localizes preferentially to pseudopodial adherent areas. Loss of PTP activity or absence of PTP-PEST leads to rapid, excessive adhesion to fibronectin and many focal adhesions; S39A cells show weak adhesion and few focal adhesions. PTP-PEST knockout MEFs, PTP-PEST WT/S39A/CS mutant re-expression, cell migration assays, fibronectin adhesion assays, focal adhesion staining, subcellular fractionation/localization Journal of Biochemistry Medium 36250939
2023 In silico modeling predicts Tyr232 of AMPKα2 as the PTP-PEST dephosphorylation site. Phosphorylation of conserved Tyr64 on PTP-PEST enhances stability of the PTP-PEST–AMPKα2 complex by rearranging electrostatic interactions and conformational changes in the catalytic WPD loop. A phosphomimetic mutant (PTP-PEST-Y64D) showed increased affinity for AMPKα2 by co-immunoprecipitation, corroborating the structural prediction. Computational structure prediction, molecular dynamics simulations, co-immunoprecipitation (Y64D phosphomimetic mutant vs WT) Proteins Low 36645312
2024 SRXN1 (sulfiredoxin-1) desulfinylates PTPN12 (reducing Cys-SO2H to Cys-SOH), which enhances PTPN12 phosphatase activity and protein stability. Active PTPN12 dephosphorylates NLRP3 on tyrosine, decreasing NLRP3 activation. A sulfinylation-resistant PTPN12 mutant (C164A) showed amplified suppression of NLRP3 activation. This SRXN1–PTPN12–NLRP3 axis attenuates hepatic stellate cell activation and liver fibrosis. HSC-specific Srxn1 knockout mice, pharmacological Srxn1 inhibition, PTPN12 overexpression, PTPN12 C164A sulfinylation-resistant mutant, NLRP3 tyrosine phosphorylation assays, liver fibrosis models Hepatology High 39446334
2024 Abl kinases phosphorylate Ptpn12, which in turn inhibits p130Cas phosphorylation and Crk recruitment, thereby regulating Rho GTPase activation and cytoskeletal dynamics. Abl kinase deficiency reduces actomyosin contractility in lens vesicle via the Ptpn12–p130Cas pathway. This places Ptpn12 downstream of Abl kinases and upstream of Crk/Rho GTPase signaling in the regulation of FGF-dependent corneal development. Genetic ablation of Abl kinases in mouse lens, epistasis with Ptpn12 phosphorylation (Abl kinase targets Ptpn12), p130Cas phosphorylation and Crk recruitment assays, RhoA/Rac1 GTPase activity, corneal/lens phenotype analysis bioRxiv (preprint)preprint Medium bio_10.1101_2024.10.24.619064
2024 Tyrosine phosphorylation at Tyr64 and Tyr88 of PTP-PEST alters loop dynamics near the catalytic site, modifies the binding pocket size, and impacts substrate binding energy as determined by computational modeling and experimental validation. Phosphorylation of Tyr64 (an interface residue) enhances PTP-PEST affinity for AMPKα2 by rearranging electrostatic interactions and WPD loop conformation. Computational (MD simulations), phosphomimetic mutants, co-immunoprecipitation, structural modeling The Journal of Physical Chemistry B Low 39423851
2019 A missense variant in PTPN12 (rs3750050) impairs PTPN12's ability to dephosphorylate SHC, thereby increasing Ras/MEK/ERK signaling, upregulating cyclin D1, and promoting aberrant cell proliferation, associated with increased colorectal cancer risk. Exome-wide association, biochemical assays (SHC dephosphorylation), ERK/cyclin D1 signaling assays in cell lines Cancer Epidemiology Medium 30731403

Source papers

Stage 0 corpus · 88 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Human molecular genetics 341 11971877
1996 Identification of p130(cas) as a substrate for the cytosolic protein tyrosine phosphatase PTP-PEST. Molecular and cellular biology 242 8887669
2011 Activation of multiple proto-oncogenic tyrosine kinases in breast cancer via loss of the PTPN12 phosphatase. Cell 235 21376233
2004 Fyn and PTP-PEST-mediated regulation of Wiskott-Aldrich syndrome protein (WASp) tyrosine phosphorylation is required for coupling T cell antigen receptor engagement to WASp effector function and T cell activation. The Journal of experimental medicine 159 14707117
2009 FAK phosphorylation by ERK primes ras-induced tyrosine dephosphorylation of FAK mediated by PIN1 and PTP-PEST. Molecular cell 145 19595712
1998 Direct association of protein-tyrosine phosphatase PTP-PEST with paxillin. The Journal of biological chemistry 145 9497381
1997 Association of PTP-PEST with the SH3 domain of p130cas; a novel mechanism of protein tyrosine phosphatase substrate recognition. Oncogene 144 9285683
1999 Regulation of fibroblast motility by the protein tyrosine phosphatase PTP-PEST. The Journal of biological chemistry 118 9920935
1994 PTP-PEST: a protein tyrosine phosphatase regulated by serine phosphorylation. The EMBO journal 117 7520867
1997 Inhibitory tyrosine protein kinase p50csk is associated with protein-tyrosine phosphatase PTP-PEST in hemopoietic and non-hemopoietic cells. The Journal of biological chemistry 113 9287362
2001 PTP-PEST, a scaffold protein tyrosine phosphatase, negatively regulates lymphocyte activation by targeting a unique set of substrates. The EMBO journal 104 11432829
2001 PSTPIP is a substrate of PTP-PEST and serves as a scaffold guiding PTP-PEST toward a specific dephosphorylation of WASP. The Journal of biological chemistry 96 11711533
1998 Combination of gene targeting and substrate trapping to identify substrates of protein tyrosine phosphatases using PTP-PEST as a model. Biochemistry 91 9748319
2002 PTP-PEST controls motility through regulation of Rac1. Journal of cell science 83 12376562
1999 Hic-5, a paxillin homologue, binds to the protein-tyrosine phosphatase PEST (PTP-PEST) through its LIM 3 domain. The Journal of biological chemistry 80 10092676
1993 Cloning and expression of PTP-PEST. A novel, human, nontransmembrane protein tyrosine phosphatase. The Journal of biological chemistry 77 8454633
2011 Ras-induced and extracellular signal-regulated kinase 1 and 2 phosphorylation-dependent isomerization of protein tyrosine phosphatase (PTP)-PEST by PIN1 promotes FAK dephosphorylation by PTP-PEST. Molecular and cellular biology 73 21876001
2006 PTP-PEST couples membrane protrusion and tail retraction via VAV2 and p190RhoGAP. The Journal of biological chemistry 56 16513648
2018 Combinatorial inhibition of PTPN12-regulated receptors leads to a broadly effective therapeutic strategy in triple-negative breast cancer. Nature medicine 55 29578538
2009 Clinical associations of the genetic variants of CTLA-4, Tg, TSHR, PTPN22, PTPN12 and FCRL3 in patients with Graves' disease. Clinical endocrinology 55 19438904
2010 The phosphatase PTP-PEST promotes secondary T cell responses by dephosphorylating the protein tyrosine kinase Pyk2. Immunity 52 20727793
2006 Essential function of PTP-PEST during mouse embryonic vascularization, mesenchyme formation, neurogenesis and early liver development. Mechanisms of development 52 17070019
2006 CD2BP1 modulates CD2-dependent T cell activation via linkage to protein tyrosine phosphatase (PTP)-PEST. Journal of immunology (Baltimore, Md. : 1950) 45 16670297
2005 Paxillin is essential for PTP-PEST-dependent regulation of cell spreading and motility: a role for paxillin kinase linker. Journal of cell science 45 16317044
2010 PTP-PEST controls motility, adherens junction assembly, and Rho GTPase activity in colon cancer cells. American journal of physiology. Cell physiology 42 20519451
2002 Roles for the tubulin- and PTP-PEST-binding paxillin LIM domains in cell adhesion and motility. The international journal of biochemistry & cell biology 42 11950600
2013 Control of dendritic cell migration, T cell-dependent immunity, and autoimmunity by protein tyrosine phosphatase PTPN12 expressed in dendritic cells. Molecular and cellular biology 41 24366546
2015 Loss of PTPN12 Stimulates Progression of ErbB2-Dependent Breast Cancer by Enhancing Cell Survival, Migration, and Epithelial-to-Mesenchymal Transition. Molecular and cellular biology 40 26391955
2007 Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells. American journal of physiology. Cell physiology 37 17329398
2013 PTPN12 promotes resistance to oxidative stress and supports tumorigenesis by regulating FOXO signaling. Oncogene 36 23435421
2006 PTP-PEST phosphatase variations in human cancer. Cancer genetics and cytogenetics 36 16965954
2012 The phosphatase PTP-PEST/PTPN12 regulates endothelial cell migration and adhesion, but not permeability, and controls vascular development and embryonic viability. The Journal of biological chemistry 34 23105101
2013 Macrophage fusion is controlled by the cytoplasmic protein tyrosine phosphatase PTP-PEST/PTPN12. Molecular and cellular biology 31 23589331
2011 Tyrosine phosphatases in the HER2-directed motility of ovarian cancer cells: Involvement of PTPN12, ERK5 and FAK. Analytical cellular pathology (Amsterdam) 30 21483099
2005 Involvement of FAK and PTP-PEST in the regulation of redox-sensitive nuclear-cytoplasmic shuttling of a LIM protein, Hic-5. Antioxidants & redox signaling 28 15706082
2012 PTPN12 controls PTEN and the AKT signalling to FAK and HER2 in migrating ovarian cancer cells. Molecular and cellular biochemistry 27 23212450
2018 PTPN12/PTP-PEST Regulates Phosphorylation-Dependent Ubiquitination and Stability of Focal Adhesion Substrates in Invasive Glioblastoma Cells. Cancer research 25 29743287
2019 Important roles of protein tyrosine phosphatase PTPN12 in tumor progression. Pharmacological research 24 30959160
2015 MVP-Associated Filamin A Mutations Affect FlnA-PTPN12 (PTP-PEST) Interactions. Journal of cardiovascular development and disease 23 26594644
2021 The protein tyrosine phosphatase PTP-PEST mediates hypoxia-induced endothelial autophagy and angiogenesis via AMPK activation. Journal of cell science 21 33323505
2003 Nitric oxide-induced inhibition of aortic smooth muscle cell motility: role of PTP-PEST and adaptor proteins p130cas and Crk. American journal of physiology. Heart and circulatory physiology 18 12714323
2015 Epigenetic regulation of protein tyrosine phosphatase PTPN12 in triple-negative breast cancer. Life sciences 17 25817229
2018 PTPN12 Affects Nasopharyngeal Carcinoma Cell Proliferation and Migration Through Regulating EGFR. Cancer biotherapy & radiopharmaceuticals 16 29634414
2006 Identification of a filamin docking site on PTP-PEST. The Journal of biological chemistry 16 16973606
2021 GABAB1e promotes the malignancy of human cancer cells by targeting the tyrosine phosphatase PTPN12. iScience 15 34778730
2020 Targeting protein tyrosine phosphatase PTP-PEST (PTPN12) for therapeutic intervention in acute myocardial infarction. Cardiovascular research 15 31228185
2019 MicroRNA-503 serves an oncogenic role in retinoblastoma progression by directly targeting PTPN12. Experimental and therapeutic medicine 15 31410179
2005 Nitric oxide attenuates IGF-I-induced aortic smooth muscle cell motility by decreasing Rac1 activity: essential role of PTP-PEST and p130cas. American journal of physiology. Cell physiology 15 16354758
2013 PTP-PEST targets a novel tyrosine site in p120 catenin to control epithelial cell motility and Rho GTPase activity. Journal of cell science 14 24284071
2012 Dynamin and PTP-PEST cooperatively regulate Pyk2 dephosphorylation in osteoclasts. The international journal of biochemistry & cell biology 14 22342188
2012 Clinicopathological significance of PTPN12 expression in human breast cancer. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 14 23044628
2007 Preliminary evidence for interaction of PTPN12 polymorphism with TSHR genotype and association with Graves' ophthalmopathy. Clinical endocrinology 14 17608818
2019 A missense variant in PTPN12 associated with the risk of colorectal cancer by modifying Ras/MEK/ERK signaling. Cancer epidemiology 13 30731403
2018 Pathologic Oxidation of PTPN12 Underlies ABL1 Phosphorylation in Hereditary Leiomyomatosis and Renal Cell Carcinoma. Cancer research 13 30297534
2013 A loss-of-function screen for phosphatases that regulate neurite outgrowth identifies PTPN12 as a negative regulator of TrkB tyrosine phosphorylation. PloS one 13 23785422
2013 miR-1279, miR-548j, miR-548m, and miR-548d-5p binding sites in CDSs of paralogous and orthologous PTPN12, MSH6, and ZEB1 Genes. BioMed research international 12 23957009
2022 LncRNA GATA2-AS1 suppresses esophageal squamous cell carcinoma progression via the mir-940/PTPN12 axis. Experimental cell research 11 35364057
2017 CD99-Derived Agonist Ligands Inhibit Fibronectin-Induced Activation of β1 Integrin through the Protein Kinase A/SHP2/Extracellular Signal-Regulated Kinase/PTPN12/Focal Adhesion Kinase Signaling Pathway. Molecular and cellular biology 11 28483911
2013 Regulation of the Src kinase-associated phosphoprotein 55 homologue by the protein tyrosine phosphatase PTP-PEST in the control of cell motility. The Journal of biological chemistry 11 23897807
2020 CD99-PTPN12 Axis Suppresses Actin Cytoskeleton-Mediated Dimerization of Epidermal Growth Factor Receptor. Cancers 9 33050232
2015 PTP-PEST controls EphA3 activation and ephrin-induced cytoskeletal remodelling. Journal of cell science 8 26644181
2004 A PTP-PEST-like protein affects alpha5beta1-integrin-dependent matrix assembly, cell adhesion, and migration in Xenopus gastrula. Developmental biology 8 14732402
2024 The desulfinylation enzyme sulfiredoxin-1 attenuates HSC activation and liver fibrosis by modulating the PTPN12-NLRP3 axis. Hepatology (Baltimore, Md.) 7 39446334
2022 Transthyretin-induced increase in circ_0007411 represses neovascularization of human retinal microvascular endothelial cells in hyperglycemia via the miR-548m/PTPN12/SKP1/EGFR pathway. Annals of translational medicine 7 35722376
2016 Identifying the role of PTPN12 expression in predicting the efficacy of capecitabine to neoadjuvant chemotherapy in breast cancer treatment. European review for medical and pharmacological sciences 7 27608899
2023 In-silico identification of Tyr232 in AMPKα2 as a dephosphorylation site for the protein tyrosine phosphatase PTP-PEST. Proteins 6 36645312
2021 Protein tyrosine phosphatase non-receptor type 12 (PTPN12), negatively regulated by miR-106a-5p, suppresses the progression of hepatocellular carcinoma. Human cell 6 34784010
2016 Hepatitis B virus mutations, expression quantitative trait loci for PTPN12, and their interactions in hepatocellular carcinoma. Cancer medicine 6 27075395
2014 Protein tyrosine phosphatase-PEST (PTP-PEST) regulates mast cell-activating signals in PTP activity-dependent and -independent manners. Cellular immunology 6 24791697
2024 PTPN1/2 inhibition promotes muscle stem cell differentiation in Duchenne muscular dystrophy. Life science alliance 5 39477543
2022 Depletion of circ_0128846 ameliorates interleukin-1β-induced human chondrocyte apoptosis and inflammation through the miR-940/PTPN12 pathway. International immunopharmacology 5 35978501
2024 Identification of PTPN12 Phosphatase as a Novel Negative Regulator of Hippo Pathway Effectors YAP/TAZ in Breast Cancer. International journal of molecular sciences 4 38612874
2020 A fluorescent probe for monitoring PTP-PEST enzymatic activity. The Analyst 4 32812952
2023 PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma. Open medicine (Warsaw, Poland) 3 37333450
2016 ACTH Modulates PTP-PEST Activity and Promotes Its Interaction With Paxillin. Journal of cellular biochemistry 3 27061092
2012 SHP-2 and PTP-pest induction during Rb-E2F associated apoptosis. Cellular & molecular biology letters 3 22644489
2025 miR-369-3p regulates the drug resistance of lung cancer cells by targeting PTPN12. Pharmacogenomics 2 40366733
2025 Dual Conjugation of Long- and Medium-Chain Fatty Acids to BimBH3 Peptide Yields Ultra Long-Acting Inhibitors of Intracellular PTPN1/2. Journal of medicinal chemistry 1 40458949
2022 PTP-PEST Regulated Membranous/Cytoplasmic Translocation of p120ctn in the Lung Cancer Resistance to Tyrosine Kinase Inhibitor. Applied immunohistochemistry & molecular morphology : AIMM 1 35030104
2020 Expression and clinical significance of PTPN12 in clear cell renal cell carcinoma. The Journal of international medical research 1 33292053
2017 Expression, purification and characterization of a catalytic domain of human protein tyrosine phosphatase non-receptor 12 (PTPN12) in Escherichia coli with FKBP-type PPIase as a chaperon. Protein expression and purification 1 28965803
2015 Mosaic partial deletion of PTPN12 in a child with interrupted aortic arch type A. American journal of medical genetics. Part A 1 26250342
2026 miR-194-5p-mediated suppression of protein tyrosine phosphatase non-receptor type 12 (PTPN12) expression in the thymus enhances immunologic functional restoration in aged mice. European journal of medical research 0 41555448
2026 PTPN12 is a novel biomarker associated with genomic instability, therapeutic potentials, and immunomodulator in colorectal cancer. Frontiers in pharmacology 0 42088574
2025 Biochemical and Structural Studies of Protein Tyrosine Phosphatase PTP-PEST (PTPN12) in Search of Small Molecule Inhibitors. Chemical biology & drug design 0 39895370
2024 Role of Tyrosine Phosphorylation in PTP-PEST. The journal of physical chemistry. B 0 39423851
2024 Erratum to Transthyretin-induced increase in circ_0007411 represses neovascularization of human retinal microvascular endothelial cells in hyperglycemia via the miR-548m/PTPN12/SKP1/EGFR pathway. Annals of translational medicine 0 40438510
2023 Phosphorylation/dephosphorylation of PTP-PEST at Serine 39 is crucial for cell migration. Journal of biochemistry 0 36250939

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