Affinage

PTPN9

Tyrosine-protein phosphatase non-receptor type 9 · UniProt P43378

Length
593 aa
Mass
68.0 kDa
Annotated
2026-06-10
46 papers in source corpus 22 papers cited in narrative 22 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

PTPN9 (PTP-MEG2) is a non-receptor protein tyrosine phosphatase that couples membrane lipid sensing to the control of secretory vesicle dynamics and the negative regulation of receptor tyrosine kinase and STAT signaling (PMID:14662869, PMID:17387180, PMID:20335174). Its catalytic activity depends on the active-site cysteine C515 and is intramolecularly restrained by an N-terminal Sec14p/lipid-binding domain, which lowers the enzyme's Vmax until it is engaged by membrane phosphoinositides; polyphosphoinositides (PI(4,5)P2 > PI(3,4,5)P3) activate the phosphatase, while opsonized zymosan or PMA stimulation inhibits it (PMID:11711529, PMID:12112018). The Sec14p domain binds phosphatidylserine and PtdIns(3,4,5)P3 and is necessary and sufficient to target the enzyme to secretory vesicle membranes, where, together with its partners TIP47 and Arfaptin2, it drives homotypic vesicle fusion (PMID:14662869, PMID:12702726, PMID:17387180). At these membranes PTP-MEG2 dephosphorylates the fusion machinery — NSF-pY83, and through NSF-independent routes DYNAMIN2-pY125 and MUNC18-1-pY145 — to regulate vesicle enlargement, fusion pore opening, and quantal secretion, and dephosphorylates the Q-SNARE VTI1B to promote SNARE assembly and ATG16L1+ autophagosome precursor fusion during autophagy (PMID:17387180, PMID:33764618, PMID:33112705). As a signaling antagonist, PTP-MEG2 directly dephosphorylates the receptor tyrosine kinases ErbB2/EGFR, VEGFR2 (Tyr1175), TrkA, FGFR2 (pY656/657, via an ACAP1 scaffold engaging its Sec14p domain), and IGF1R (Y1166), and dephosphorylates cytoplasmic STAT3 at Tyr705 to suppress STAT3-dependent transcription (PMID:20335174, PMID:22763125, PMID:27655914, PMID:37505213, PMID:41275311, PMID:22394684). Through these activities it restrains growth-factor and cytokine signaling, controls erythroid maturation by relieving STAT3-mediated sequestration of GATA1/ZBP-89 (PMID:24727614), and antagonizes hepatic insulin receptor signaling and FOXO1 nuclear exclusion, such that its depletion normalizes hyperglycemia in db/db mice (PMID:16679294). Genetic loss in mice causes late embryonic lethality with secretory and hematopoietic defects, underscoring its essential role in regulated secretion (PMID:16330817).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2001 High

    Established the catalytic and regulatory architecture of MEG2 — that activity requires Cys515 and is autoinhibited by the N-terminal domain and tuned by lipids — defining how a phosphatase could be membrane-regulated.

    Evidence Cell fractionation, in vitro phosphatase assay, and GST-fusion mutagenesis (C515) with lipid activation in neutrophils

    PMID:11711529

    Open questions at the time
    • Did not identify physiological protein substrates
    • Mechanism by which lipids relieve N-terminal autoinhibition not resolved structurally
  2. 2002 High

    Showed catalytic activity controls secretory vesicle morphology and secretion, linking the phosphatase to regulated exocytosis rather than generic signaling.

    Evidence Overexpression in mast and Jurkat T cells with EM, IL-2 secretion assays, and catalytic mutant rescue; in vitro kinetics of full-length vs. truncated enzyme

    PMID:11971009 PMID:12112018

    Open questions at the time
    • Vesicle substrate(s) at the fusion machinery not yet identified
    • Connection between enlargement and secretion block mechanistically unclear
  3. 2003 High

    Defined the Sec14p domain as a lipid sensor binding phosphatidylserine and PtdIns(3,4,5)P3 that targets the enzyme to vesicle membranes and is required for homotypic fusion, explaining how membrane lipids spatially control activity.

    Evidence In vitro lipid overlay/liposome binding, domain mapping, point mutagenesis, colocalization, and PI3K inhibitor perturbation

    PMID:12702726 PMID:14662869

    Open questions at the time
    • Did not identify the dephosphorylated fusion substrate
    • Membrane partner proteins not yet defined
  4. 2005 High

    Genetic knockout established the organismal essentiality of MEG2 and confirmed its requirement for mature secretory vesicle biogenesis and immune cell activation.

    Evidence Meg2-/- mice and RAG2-/- hematopoietic chimeras with T cell/platelet activation assays, EM, and lipid binding

    PMID:16330817

    Open questions at the time
    • Embryonic lethality obscures tissue-specific roles
    • Molecular substrate driving vesicle maturation not pinpointed here
  5. 2006 High

    Placed MEG2 as a negative regulator of insulin receptor signaling in liver, establishing a metabolic role and a therapeutic rationale.

    Evidence Functional screen, FOXO1 localization imaging, RNAi/ectopic expression, and adenoviral liver depletion in db/db mice

    PMID:16679294

    Open questions at the time
    • Direct dephosphorylation of the insulin receptor by MEG2 not biochemically demonstrated here
    • Relationship to its vesicular role unaddressed
  6. 2007 High

    Identified TIP47 and Arfaptin2 as direct Sec14p-domain partners and NSF as a fusion substrate, providing the molecular machinery linking membrane targeting to vesicle fusion.

    Evidence Yeast two-hybrid, deletion mapping, Co-IP, TIP47 knockdown, and localization imaging

    PMID:17387180

    Open questions at the time
    • NSF dephosphorylation site not defined in this study
    • How TIP47/Arfaptin2 coordinate with lipid binding unresolved
  7. 2010 High

    Established MEG2 as a direct phosphatase for ErbB2 and EGFR with substrate selectivity, extending its role to receptor tyrosine kinase signaling and downstream STAT activation.

    Evidence Substrate-trapping DA mutant Co-IP/GST pulldown, gain/loss of function, and STAT activation readouts

    PMID:20335174

    Open questions at the time
    • Subcellular site of RTK dephosphorylation not localized
    • Whether vesicular targeting is required for RTK access unclear
  8. 2012 High

    Demonstrated direct STAT3 binding and Tyr705 dephosphorylation in the cytoplasm, and identified VEGFR2-Tyr1175 and JAK1 as additional targets, broadening MEG2 as a cytokine/growth-factor signaling brake.

    Evidence Co-IP and biochemical dephosphorylation in breast cancer cells; substrate-trapping Co-IP and phospho-immunoblot for VEGFR2/JAK1 in endothelial cells

    PMID:22394684 PMID:22763125

    Open questions at the time
    • VEGFR2 and JAK1 findings from a single lab
    • Spatial coordination of STAT3 vs. RTK dephosphorylation not defined
  9. 2012 High

    Crystal structures of inhibitor complexes revealed unique peripheral pockets enabling selective inhibition and provided in vivo proof that pharmacological inhibition augments insulin signaling.

    Evidence X-ray crystallography of inhibitor complexes, phosphatase inhibition assays, and diet-induced obese mouse model

    PMID:23075115

    Open questions at the time
    • No substrate-bound structure in this study
    • Selectivity over closely related phosphatases in cells not fully mapped
  10. 2014 High

    Connected MEG2-STAT3 regulation to erythroid maturation, showing loss elevates pSTAT3 which sequesters GATA1/ZBP-89, defining a developmental output of the phosphatase.

    Evidence Zebrafish morpholino knockdown, dominant-negative and siRNA in K562, and Co-IP of the STAT3-GATA1-ZBP89 complex

    PMID:24727614

    Open questions at the time
    • Whether reduced erythroid maturation reflects STAT3 alone or additional substrates unclear
  11. 2016 Medium

    Identified TrkA as both a substrate and a cargo, uniting MEG2's dephosphorylation and vesicle-fusion functions in controlling neurotrophin receptor surface delivery and neurite outgrowth.

    Evidence Substrate-trapping, phospho-site mapping (Y490, Y674/675), and neurite outgrowth assays in PC12 cells and cortical neurons

    PMID:27655914

    Open questions at the time
    • Single-lab finding
    • Quantitative contribution of trafficking vs. direct dephosphorylation to signaling output not separated
  12. 2020 High

    Extended the vesicle-fusion role into autophagy by identifying VTI1B as a Q-SNARE substrate required for ATG16L1+ precursor fusion, with conservation in Drosophila.

    Evidence siRNA in mammalian cells, Drosophila RNAi, phospho-mutant epistasis, SNARE assembly and autophagic flux assays

    PMID:33112705

    Open questions at the time
    • Lipid/partner requirements for autophagosomal targeting not dissected
    • Upstream signals controlling VTI1B phosphorylation unknown
  13. 2021 High

    Provided structural basis for substrate selectivity at the fusion machinery, showing distinct interfaces for NSF-pY83 versus DYNAMIN2-pY125 and MUNC18-1-pY145 controlling separable secretion steps.

    Evidence X-ray crystallography of substrate-enzyme complexes, mutagenesis, and electrochemical catecholamine secretion assays

    PMID:33764618

    Open questions at the time
    • How the same active site discriminates multiple substrates in cells not fully resolved
    • Regulation of step-specific substrate engagement unknown
  14. 2023 High

    Defined a scaffolded mechanism whereby ACAP1 bridges the Sec14p domain of PTPN9 to FGFR2, enabling pY656/657 dephosphorylation and modulating FGFR-inhibitor response in cholangiocarcinoma.

    Evidence Co-IP, phosphatase assays, structural modeling/mutagenesis (YRETRRKE motif, Y471; ACAP1 PH/Arf-GAP), and PDX models

    PMID:37505213

    Open questions at the time
    • Whether ACAP1 scaffolding generalizes to other RTK substrates unknown
    • I654V resistance mechanism beyond reduced interaction not fully detailed
  15. 2024 Medium

    Revealed competitive regulation of STAT3 by MEG2 and PKCε and an ERK1/2-facilitated MEG2-STAT3 interaction, refining how MEG2 access to STAT3 is controlled in inflammatory contexts.

    Evidence Reciprocal Co-IP/competition, luciferase, and in vivo/in vitro inflammatory pain models

    PMID:38656553

    Open questions at the time
    • Single-lab competition model
    • Structural basis of competitive STAT3 binding not resolved
  16. 2025 High

    Identified IGF1R-Y1166 as a substrate with structural definition of the interface (Tyr333, Asp335), linking PTPN9 tumor suppression to IGF1R signaling in cholangiocarcinoma.

    Evidence IP-MS, crystal structure analysis, biochemical dephosphorylation, active-site mutagenesis, and orthotopic mouse models

    PMID:41275311

    Open questions at the time
    • Single-lab finding
    • Integration with parallel RTK substrates in the same tumor context not addressed
  17. 2026 Medium

    Placed the ERK1/2-facilitated MEG2-STAT3 axis in a viral context, showing SARS-CoV-2 Mpro signaling drives STAT3 Tyr705 dephosphorylation and ACE2 suppression.

    Evidence Mpro overexpression/catalytic mutant, ERK1/2 inhibitor rescue, Co-IP, and single-round infectious particle assays

    PMID:41728757

    Open questions at the time
    • Single-lab pathway model
    • Direct ERK1/2 modification mediating MEG2-STAT3 assembly not biochemically defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single phosphatase coordinates its membrane-bound vesicle-fusion substrates with cytoplasmic RTK/STAT3 substrates — and what spatial or lipid cues partition these activities in vivo — remains unresolved.
  • No unified model linking lipid-regulated localization to substrate choice
  • Tissue-specific substrate priorities largely uncharacterized
  • In vivo relevance of individual RTK substrates outside cancer models unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0008289 lipid binding 4 GO:0098772 molecular function regulator activity 3 GO:0016787 hydrolase activity 2
Localization
GO:0031410 cytoplasmic vesicle 4 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-9612973 Autophagy 1
Partners
ACAP1EGFRERBB2FGFR2NSFSTAT3TIP47VEGFR2

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 PTPN9 directly dephosphorylates ErbB2 and EGFR (but not ErbB3 or Shc) as substrates, demonstrated by substrate-trapping mutant (DA) co-immunoprecipitation and GST pulldown showing preferential association with phospho-ErbB2/EGFR, and by WT overexpression inhibiting while DA mutant enhancing their tyrosyl phosphorylation. PTPN9 WT expression also specifically impairs EGF-induced STAT3 and STAT5 activation. Substrate-trapping mutant (DA) overexpression, co-immunoprecipitation, GST-fusion pulldown, siRNA knockdown, soft agar growth assay The Journal of biological chemistry High 20335174
2012 PTPN9 (PTPMeg2) directly interacts with STAT3 and mediates its dephosphorylation in the cytoplasm; overexpression decreases STAT3 tyrosine phosphorylation and suppresses STAT3 transcriptional activity, while depletion increases phosphorylation. Immunoprecipitation, biochemical dephosphorylation assays, siRNA knockdown, overexpression in MCF7 and MDA-MB-231 cells, in vivo tumor growth assay Breast cancer research : BCR High 22394684
2002 Overexpression of PTP-MEG2 causes striking enlargement of secretory vesicles in mast cells and Jurkat T cells and reduces IL-2 secretion; these effects require the catalytic activity of PTP-MEG2 (reversed by pervanadate and abolished by catalytic mutants). Overexpression in RBL mast cells and Jurkat T cells, immunofluorescence, electron microscopy, IL-2 secretion assay, catalytic mutant analysis Journal of immunology High 11971009
2003 The N-terminal Sec14p homology domain of PTP-MEG2 binds PtdIns(3,4,5)P3 in vitro and colocalizes with this lipid on secretory vesicle membranes; point mutations preventing PtdIns(3,4,5)P3 binding abolish homotypic secretory vesicle fusion. Inhibition of cellular PtdIns(3,4,5)P3 synthesis rapidly reverses vesicle fusion by PTP-MEG2. In vitro lipid binding assay, point mutagenesis, immunofluorescence colocalization, PI3K inhibitor treatment, cell-based vesicle fusion assay Journal of immunology High 14662869
2003 PTP-MEG2 specifically binds phosphatidylserine among >20 lipids tested, mediated by its N-terminal Sec14 domain; the Sec14 domain is responsible for perinuclear localization of PTP-MEG2 in intact cells, and exogenous phosphatidylserine loading causes translocation of PTP-MEG2 to the plasma membrane. Lipid-membrane overlay assay, liposome binding assay, deletion mutant analysis, cell fractionation/immunofluorescence localization The Journal of biological chemistry High 12702726
2001 MEG2 is localized predominantly in the cytosol with components in secondary/tertiary granules and secretory vesicles of neutrophils, and associates at an early stage with nascent phagosomes. Cysteine 515 is essential for catalytic activity. The N-terminal domain negatively regulates enzymatic activity of the C-terminal phosphatase domain. PTP-MEG2 activity is activated by polyphosphoinositides (PI 4,5-P2 > PI 3,4,5-P3 > PI 4-P) and inhibited by opsonized zymosan or PMA stimulation. Immunofluorescence, cell fractionation, immunoblotting, immunoprecipitation, in vitro phosphatase assay, GST-fusion protein mutagenesis (C515 mutation) The Journal of biological chemistry High 11711529
2002 Purified full-length PTP-MEG2 exhibits classical Michaelis-Menten kinetics with pNPP and phosphotyrosine substrates; the N-terminal lipid-binding domain has an inhibitory role on catalytic activity (truncated form lacking the domain shows significantly higher Vmax and lower Km than full-length enzyme). Recombinant protein purification (adenovirus and E. coli expression), in vitro phosphatase kinetics assay, gel exclusion chromatography Journal of cellular biochemistry High 12112018
2005 MEG2-deficient mice show >90% late embryonic lethality with hemorrhages, neural tube defects, and bone abnormalities. T lymphocytes and platelets from Meg2-/- hematopoietic chimeras display profound activation defects; T lymphocytes show impaired IL-2 secretion with near-complete absence of mature secretory vesicles by ultrastructural analysis. MEG2 binds PI(4,5)P2 and PI(3,4,5)P3 via its N-terminal lipid-binding domain. Knockout mouse generation, hematopoietic reconstitution (RAG2-/- chimeras), T cell activation assays, platelet activation assays, electron microscopy, lipid binding assay The Journal of experimental medicine High 16330817
2006 PTP-MEG2 antagonizes hepatic insulin signaling: ectopic expression inhibits insulin-induced phosphorylation of the insulin receptor and blocks insulin-dependent FOXO1 nuclear exclusion, while RNAi-mediated reduction enhances insulin action. Adenoviral depletion of PTP-MEG2 in livers of diabetic db/db mice normalizes hyperglycemia. Genome-scale functional screen, quantitative image analysis of FOXO1 localization, ectopic expression, RNAi knockdown, adenoviral liver-specific depletion in db/db mice, glucose homeostasis measurements Cell metabolism High 16679294
2007 The N-terminal Sec14p domain (residues 1–261) of PTPMEG2 is necessary and sufficient for targeting to secretory vesicle membranes. Yeast two-hybrid screening identified TIP47 and Arfaptin2 as direct binding partners of the SEC14 domain; TIP47 overexpression alters PTPMEG2 localization and elimination of TIP47 causes loss of PTPMEG2 function. PTPMEG2 dephosphorylates NSF (N-ethylmaleimide-sensitive factor) to promote homotypic vesicle fusion. Deletion mutant analysis, yeast two-hybrid screen, Co-IP, overexpression/knockdown of TIP47, subcellular localization imaging The Journal of biological chemistry High 17387180
2003 Elevated PTP-MEG2 activity in polycythemia vera (PV) erythroid progenitor cells is due to increased distribution of PTP-MEG2 in the membrane fraction. Expression of dominant-negative mutant forms of PTP-MEG2 suppresses in vitro growth and expansion of both normal and PV erythroid colony-forming cells. Cell fractionation, phosphatase activity assay, dominant-negative mutant overexpression, colony-forming assay Blood Medium 12920026
2012 PTP-MEG2 dephosphorylates VEGFR2 at Tyr1175 (a critical autophosphorylation site) in endothelial cells; substrate-trapping DA mutant preferentially co-immunoprecipitates with VEGFR2 but not WT PTP-MEG2. PTP-MEG2 DA mutant also preferentially associates with JAK1 (but not Tyk2 or JAK2) and regulates JAK1 tyrosine phosphorylation. PTP-MEG2 knockdown enhances VEGF-induced IL-6 production. Substrate-trapping (DA) mutant co-immunoprecipitation, overexpression/knockdown, phospho-specific immunoblotting, IL-6 ELISA American journal of physiology. Cell physiology Medium 22763125
2012 Crystal structures of PTP-MEG2–inhibitor complexes reveal that potent and selective inhibition is achieved by engaging both the active site and unique peripheral binding pockets on PTP-MEG2, with F2Pmp scaffold modifications providing selectivity. A selective cell-permeable inhibitor augments insulin signaling and improves glucose homeostasis in diet-induced obese mice. X-ray crystallography of inhibitor complexes, in vitro phosphatase inhibition assays, cell-based insulin signaling assays, diet-induced obese mouse model Journal of the American Chemical Society High 23075115
2014 Zebrafish ptpn9a is required for erythroid cell maturation; morpholino knockdown of ptpn9a impairs erythrocyte maturation and increases phosphorylated STAT3. Hyper-phosphorylated STAT3 sequesters transcription factors GATA1 and ZBP-89 into an inhibitory complex, preventing erythroid gene expression. Both dominant-negative PTPN9 (C515S) and siRNA in human K562 cells inhibit erythroid differentiation. Morpholino knockdown in zebrafish, dominant-negative overexpression, siRNA in K562 cells, immunoprecipitation, erythroid differentiation assays Journal of cell science High 24727614
2016 PTP-MEG2 identifies TrkA (neurotrophin receptor) as a novel substrate and cargo; PTP-MEG2 dephosphorylates both Tyr-490 and Tyr-674/Tyr-675 of TrkA, and also facilitates TrkA transport to the cell surface via its vesicle fusion activity (dephosphorylation of NSF). Overexpression of PTP-MEG2 down-regulates NGF/TrkA signaling and blocks neurite outgrowth and differentiation in PC12 cells and cortical neurons. Substrate-trapping mutant, phospho-specific immunoblotting, neurite outgrowth assay in PC12 cells, overexpression in cortical neurons The Journal of biological chemistry Medium 27655914
2020 PTPN9 promotes homotypic fusion of ATG16L1+ autophagosome precursor vesicles and is required for autophagosome formation and autophagic flux. PTPN9 dephosphorylates the Q-SNARE VTI1B; the nonphosphorylatable VTI1B mutant (but not phosphomimetic) enhances SNARE complex assembly and autophagic flux. Loss of PTPN9 and its Drosophila homolog Ptpmeg2 impairs autophagosome formation. siRNA knockdown in mammalian cells, RNAi in Drosophila, immunofluorescence colocalization, phospho-mutant analysis, SNARE complex assembly assay, autophagic flux assay Autophagy High 33112705
2021 PTP-MEG2 controls multiple steps of catecholamine secretion. Crystallographic and biochemical analyses reveal key residues governing PTP-MEG2 interaction with phosphorylated NSF-pY83, specifying substrate selectivity and modulating vesicle fusion. PTP-MEG2 controls fusion pore opening through NSF-independent mechanisms by dephosphorylating DYNAMIN2-pY125 and MUNC18-1-pY145, with a distinct structural basis from the NSF-pY83 interaction. X-ray crystallography, biochemical interaction assays, electrochemical secretion assays, site-directed mutagenesis, bioinformatics substrate screening EMBO reports High 33764618
2023 PTPN9 interacts with FGFR2 through ACAP1 mediation (via the Sec14p domain of PTPN9) and dephosphorylates FGFR2 at pY656/657. Key interaction residues include the 'YRETRRKE' motif of Sec14p, Y471 of PTPN9, and the PH and Arf-GAP domains of ACAP1. The FGFR2 I654V substitution decreases PTPN9-FGFR2 interaction and reduces pemigatinib effectiveness. PTPN9 synergistically enhances pemigatinib efficacy in cholangiocarcinoma. Co-immunoprecipitation, phosphatase activity assays, structural modeling of FGFR2-PTPN9 complex, site-directed mutagenesis, patient-derived xenograft models, in vitro and in vivo functional experiments Hepatology High 37505213
2018 MEG2 inhibits AKT phosphorylation in hepatocellular carcinoma cells; MEG2 overexpression inhibits EMT and AKT phosphorylation, and the promoting effects of MEG2 knockdown on cell viability, migration, and invasion are blocked by AKT phosphorylation inhibition, placing MEG2 upstream of AKT in this pathway. Western blot, overexpression and siRNA knockdown, cell viability/migration/invasion assays, AKT inhibitor epistasis, subcutaneous and tail-vein injection mouse models Gene Medium 30399427
2024 MEG2 and PKCε competitively bind STAT3; PKCε displays stronger binding to STAT3 than MEG2. STAT3 Ser727 phosphorylation increases interaction with both PKCε and MEG2. MEG2 binding to STAT3 suppresses IL-6 promoter activity and reduces inflammatory pain signaling in microglia, while PKCε promotes it. ERK1/2 facilitates MEG2-STAT3 interaction leading to STAT3 Tyr705 dephosphorylation. Co-immunoprecipitation, ELISA, dual-luciferase assay, Western blot, overexpression in vivo (FCA mouse model) and in vitro (LPS-stimulated microglia), von Frey test FASEB journal Medium 38656553
2025 PTPN9 dephosphorylates IGF1R preferentially at Y1166 (within the Y1165/1166 activation loop); crystal structure analysis identified Tyr333 and Asp335 as key PTPN9 residues interacting with IGF1R, and mutation of these residues restores IGF1R signaling and abolishes tumor-suppressive effects of PTPN9 in cholangiocarcinoma. IP-MS substrate identification, crystal structure analysis, biochemical dephosphorylation assay, site-directed mutagenesis, orthotopic mouse models, surufatinib-resistant cell line Journal of experimental & clinical cancer research High 41275311
2026 ERK1/2 (activated by SARS-CoV-2 Mpro via TRAF6-TAK1 signaling) facilitates interaction between STAT3 and MEG2, leading to dephosphorylation of STAT3 at Tyr705 and suppression of ACE2 expression; ERK1/2 inhibition restores STAT3 activity and ACE2 levels. Overexpression of Mpro and catalytic mutant, ERK1/2 inhibitor treatment, immunoprecipitation, Western blot for pSTAT3/ACE2, SARS-CoV-2 single-round infectious particles Journal of medical virology Medium 41728757

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling. Journal of cell science 130 23418360
2016 miR-96 promotes cell proliferation, migration and invasion by targeting PTPN9 in breast cancer. Scientific reports 91 27857177
2012 Protein tyrosine phosphatase Meg2 dephosphorylates signal transducer and activator of transcription 3 and suppresses tumor growth in breast cancer. Breast cancer research : BCR 67 22394684
2010 Protein-tyrosine phosphatase PTPN9 negatively regulates ErbB2 and epidermal growth factor receptor signaling in breast cancer cells. The Journal of biological chemistry 65 20335174
2006 Identification of the tyrosine phosphatase PTP-MEG2 as an antagonist of hepatic insulin signaling. Cell metabolism 53 16679294
2002 Enlargement of secretory vesicles by protein tyrosine phosphatase PTP-MEG2 in rat basophilic leukemia mast cells and Jurkat T cells. Journal of immunology (Baltimore, Md. : 1950) 49 11971009
2012 A highly selective and potent PTP-MEG2 inhibitor with therapeutic potential for type 2 diabetes. Journal of the American Chemical Society 44 23075115
2005 Tyrosine phosphatase MEG2 modulates murine development and platelet and lymphocyte activation through secretory vesicle function. The Journal of experimental medicine 42 16330817
2017 MEG2 is regulated by miR-181a-5p and functions as a tumour suppressor gene to suppress the proliferation and migration of gastric cancer cells. Molecular cancer 39 28747184
2003 PTP-MEG2 is activated in polycythemia vera erythroid progenitor cells and is required for growth and expansion of erythroid cells. Blood 39 12920026
2003 Homotypic secretory vesicle fusion induced by the protein tyrosine phosphatase MEG2 depends on polyphosphoinositides in T cells. Journal of immunology (Baltimore, Md. : 1950) 37 14662869
2001 Protein-tyrosine phosphatase MEG2 is expressed by human neutrophils. Localization to the phagosome and activation by polyphosphoinositides. The Journal of biological chemistry 35 11711529
2008 MEG-1 and MEG-2 are embryo-specific P-granule components required for germline development in Caenorhabditis elegans. Genetics 33 18202375
2003 Specific interaction of protein tyrosine phosphatase-MEG2 with phosphatidylserine. The Journal of biological chemistry 30 12702726
2007 Association of protein-tyrosine phosphatase MEG2 via its Sec14p homology domain with vesicle-trafficking proteins. The Journal of biological chemistry 28 17387180
2002 Purification and characterization of protein tyrosine phosphatase PTP-MEG2. Journal of cellular biochemistry 24 12112018
2021 BMSCs-Derived Exosomal MiR-126-3p Inhibits the Viability of NSCLC Cells by Targeting PTPN9. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 22 34761590
2020 Ropivacaine inhibits cervical cancer cell growth via suppression of the miR‑96/MEG2/pSTAT3 axis. Oncology reports 19 32323811
2016 The Protein Tyrosine Phosphatase MEG2 Regulates the Transport and Signal Transduction of Tropomyosin Receptor Kinase A. The Journal of biological chemistry 19 27655914
2012 Tyrosine phosphatase PTP-MEG2 negatively regulates vascular endothelial growth factor receptor signaling and function in endothelial cells. American journal of physiology. Cell physiology 19 22763125
2018 MiR-613 promotes cell proliferation and invasion in cervical cancer via targeting PTPN9. European review for medical and pharmacological sciences 17 30024598
2019 PTPN9 induces cell apoptosis by mitigating the activation of Stat3 and acts as a tumor suppressor in colorectal cancer. Cancer management and research 16 30804683
2018 MiR-96 enhances cellular proliferation and tumorigenicity of human cervical carcinoma cells through PTPN9. Saudi journal of biological sciences 15 30108433
2014 Protein tyrosine phosphatase PTPN9 regulates erythroid cell development through STAT3 dephosphorylation in zebrafish. Journal of cell science 15 24727614
2023 PTPN9 dephosphorylates FGFR2 pY656/657 through interaction with ACAP1 and ameliorates pemigatinib effect in cholangiocarcinoma. Hepatology (Baltimore, Md.) 14 37505213
2020 PTPN9-mediated dephosphorylation of VTI1B promotes ATG16L1 precursor fusion and autophagosome formation. Autophagy 13 33112705
2015 Downregulated Expression of PTPN9 Contributes to Human Hepatocellular Carcinoma Growth and Progression. Pathology oncology research : POR 13 26715439
2018 Methyllucidone inhibits STAT3 activity by regulating the expression of the protein tyrosine phosphatase MEG2 in DU145 prostate carcinoma cells. Bioorganic & medicinal chemistry letters 12 29456111
2017 PTPN9 promotes cell proliferation and invasion in Eca109 cells and is negatively regulated by microRNA-126. Oncology letters 11 28789358
2011 C. elegans meg-1 and meg-2 differentially interact with nanos family members to either promote or inhibit germ cell proliferation and survival. Genesis (New York, N.Y. : 2000) 10 21305687
2020 The Critical Role of the miR-21-MEG2 Axis in Colorectal Cancer. Critical reviews in eukaryotic gene expression 9 33463918
2018 Heterozygous Meg2 Ablation Causes Intraocular Pressure Elevation and Progressive Glaucomatous Neurodegeneration. Molecular neurobiology 9 30315478
2023 Signature of miR-21 and MEG-2 and their correlation with TGF-β signaling in breast cancer. Human & experimental toxicology 8 36825546
2021 Phloridzin Acts as an Inhibitor of Protein-Tyrosine Phosphatase MEG2 Relevant to Insulin Resistance. Molecules (Basel, Switzerland) 8 33799458
2024 Exploring the Anti-Diabetic Potential of Quercetagitrin through Dual Inhibition of PTPN6 and PTPN9. Nutrients 7 38474775
2021 Effect of L3MBTL3/PTPN9 polymorphisms on risk to alcohol-induced ONFH in Chinese Han population. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 7 34373992
2021 PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates. EMBO reports 6 33764618
2019 Design, synthesis, biological evaluation and molecular dynamics simulation studies of (R)-5-methylthiazolidin-4-One derivatives as megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2) inhibitors for the treatment of type 2 diabetes. Journal of biomolecular structure & dynamics 6 31402760
2018 MEG2 inhibits the growth and metastasis of hepatocellular carcinoma by inhibiting AKT pathway. Gene 6 30399427
2024 The binding of PKCε and MEG2 to STAT3 regulates IL-6-mediated microglial hyperalgesia during inflammatory pain. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 5 38656553
2021 Tyrosine-Protein Phosphatase Non-receptor Type 9 (PTPN9) Negatively Regulates the Paracrine Vasoprotective Activity of Bone-Marrow Derived Pro-angiogenic Cells: Impact on Vascular Degeneration in Oxygen-Induced Retinopathy. Frontiers in cell and developmental biology 5 34124069
2016 Virtual screening, optimization, and identification of a novel specific PTP-MEG2 Inhibitor with potential therapy for T2DM. Oncotarget 5 27384997
2017 Synthesis, bioactivity, 3D-QSAR studies of novel dibenzofuran derivatives as PTP-MEG2 inhibitors. Oncotarget 3 28388567
2025 PTPN9 promotes melanoma progression by regulating the ferroptosis pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 39937573
2026 SARS-CoV-2 Main Protease Activates ERK1/2 Signaling to Facilitate MEG2-STAT3-Mediated Suppression of ACE2. Journal of medical virology 0 41728757
2025 PTPN9 dephosphorylates IGF1RY1165/1166 and alleviates IGF1R-mediated resistance to tyrosine kinase inhibitor in cholangiocarcinoma. Journal of experimental & clinical cancer research : CR 0 41275311

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