Affinage

PTPRZ1

Receptor-type tyrosine-protein phosphatase zeta · UniProt P23471

Length
2315 aa
Mass
254.6 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTPRZ1 encodes RPTPβ/ζ, a CNS-enriched receptor-type protein tyrosine phosphatase whose entire extracellular domain is also produced as a secreted chondroitin sulfate proteoglycan, phosphacan, by alternative splicing (PMID:7511813). Through this ectodomain, PTPRZ1 acts as a multivalent adhesion and growth-factor hub: phosphacan binds neural CAMs N-CAM and Ng-CAM/L1 with high affinity to inhibit neuronal adhesion and neurite growth, an interaction mediated principally by N-linked complex-type oligosaccharides at Asn-232 and Asn-381 rather than its chondroitin sulfate chains (PMID:7528221, PMID:7559574), while it engages TAG-1/axonin-1 predominantly through chondroitin sulfate chains (PMID:8663515, PMID:36227633). The core protein further binds the fibrinogen-globe domain of tenascin-C and tenascin-R and captures growth factors pleiotrophin and FGF-2, potentiating their biological activity (PMID:7512960, PMID:9182584, PMID:9705269); chondroitin sulfate structural heterogeneity tunes pleiotrophin binding affinity (PMID:12840014). A structurally defined RPTPζ–tenascin-R protein-protein interface is required for assembly of reticulated perineuronal nets in vivo, a phenotype lost in Ptprz1-knockout mice (PMID:31822561, PMID:37356715). Phosphacan is a major brain carrier of O-mannose-linked glycan epitopes including HNK-1 and Lewis X, synthesized via POMGnT1-dependent O-mannosylation (PMID:22728091, PMID:24352591, PMID:25361541). As a signaling receptor, PTPRZ1 binds pleiotrophin to control tyrosine phosphorylation of substrates including calmodulin, ALK and TrkA, and directly dephosphorylates RNF26 at Y432 to stabilize it and activate TNF/NF-κB signaling (PMID:23170925, PMID:29753117, PMID:39443724). PTPRZ1 also nucleates an ERBB4–MAGI kinase/phosphatase complex and drives β-catenin nuclear translocation with downstream cyclin D1/c-myc induction (PMID:17579610, PMID:18055543). In glioblastoma, a recurrent PTPRZ1-MET (ZM) chromosomal fusion generates a protein that, via a PTPRZ1-derived coiled-coil, drives ligand-independent MET dimerization and activation to promote migration, invasion and immunosuppressive macrophage recruitment (PMID:25135958, PMID:33645009, PMID:38685521); paracrine pleiotrophin–PTPRZ1 signaling sustains glioma stem cell maintenance, and the PTN/PTPRZ1 axis activates c-Met/mTORC1 signaling in tumor and endothelial cells (PMID:28569747, PMID:39409168).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1994 High

    Establishing that the secreted brain proteoglycan phosphacan is the ectodomain of a receptor tyrosine phosphatase unified an adhesion molecule and a signaling receptor into one gene product.

    Evidence cDNA cloning, peptide sequencing and domain-specific RNA analysis

    PMID:7511813

    Open questions at the time
    • Functional consequence of the transmembrane/phosphatase isoforms not addressed here
    • No substrate of the intracellular domain identified at this stage
  2. 1994 High

    Quantitative binding assays defined phosphacan as a high-affinity ligand for neural CAMs and tenascin-C that modulates adhesion, answering what its ectodomain does at the cell surface.

    Evidence Radioligand binding, Scatchard analysis, chondroitinase treatment and adhesion/neurite assays

    PMID:7512960 PMID:7528221

    Open questions at the time
    • Molecular basis of binding (glycan vs core protein) only partially resolved
    • In vivo relevance untested
  3. 1995 High

    Mapping the binding determinants to specific N-linked oligosaccharides versus chondroitin sulfate established that distinct ligands engage phosphacan through distinct molecular surfaces.

    Evidence Tryptic-fragment binding assays, glycosidase treatments and glycopeptide sequencing; later extended to TAG-1, FGF-2 and tenascin domains

    PMID:7559574 PMID:8663515 PMID:9182584 PMID:9705269

    Open questions at the time
    • Structural model of the binding interface not available
    • Whether full-length receptor uses the same determinants unclear
  4. 1996 High

    Identification of pleiotrophin as a high-affinity, functionally required phosphacan ligand connected the proteoglycan to growth-factor signaling and neurite outgrowth.

    Evidence Affinity chromatography, Scatchard binding, antibody-blocking neurite outgrowth assays; chondroitin sulfate shown to tune affinity

    PMID:10840014 PMID:8702927

    Open questions at the time
    • Downstream signaling from the receptor not yet defined
    • Receptor versus secreted form roles not separated
  5. 2003 Medium

    Discovery that developmental chondroitin sulfate fine structure tunes pleiotrophin affinity, plus identification of a novel non-proteoglycan PSI isoform, revealed glycan- and splicing-based regulation of ligand engagement.

    Evidence SPR with defined disaccharide composition; cDNA cloning and binding/neurite assays for PSI

    PMID:12700241 PMID:12840014

    Open questions at the time
    • PSI characterized in a single lab
    • In vivo significance of glycan tuning untested
  6. 2007 Medium

    Showing PTPRZ1 forms an ERBB4–MAGI scaffold complex and drives β-catenin nuclear translocation linked the phosphatase to defined intracellular signaling axes.

    Evidence Yeast two-hybrid, reciprocal Co-IP, phosphorylation assays; siRNA with nuclear β-catenin and proliferation readouts

    PMID:17579610 PMID:18055543

    Open questions at the time
    • Direct substrate of the phosphatase not identified
    • Single-lab findings
  7. 2010 High

    Identification of Egr-1, HIF-2α/ELK1, later HOXA5 and integrin-α6β4/UCHL1/Hif-1α as transcriptional drivers defined how PTPRZ1 expression is controlled in reactive and tumor contexts.

    Evidence Promoter mutagenesis, ChIP, reporter assays and knockout/knockdown validation across multiple studies

    PMID:18556777 PMID:20224786 PMID:35219772 PMID:39518121

    Open questions at the time
    • Relative contribution of each factor in normal CNS unclear
    • Cross-talk among regulators not integrated
  8. 2013 High

    Establishing phosphacan as the major brain carrier of O-mannose-linked HNK-1 and Lewis X glycans, dependent on POMGnT1, tied PTPRZ1 glycosylation to muscle-eye-brain disease glycobiology.

    Evidence Mass spectrometry of O-linked glycans with GlcAT-P, β4GalT2 and POMGnT1 knockout mice

    PMID:22728091 PMID:24352591 PMID:25361541 PMID:25737452

    Open questions at the time
    • Functional consequence of specific glycoforms on ligand binding not directly tested
    • Link to disease phenotype correlative
  9. 2014 High

    Characterizing the recurrent PTPRZ1-MET fusion and its ligand-independent MET activation explained an oncogenic gain-of-function mechanism in glioblastoma.

    Evidence RNA-seq/genomic translocation analysis, overexpression migration/invasion assays, structure prediction and clinical MET signaling validation

    PMID:25135958 PMID:25935522 PMID:33645009 PMID:38685521

    Open questions at the time
    • Contribution of the PTPRZ1 promoter versus coiled-coil to activation not fully separated
    • Therapeutic vulnerability validation incomplete
  10. 2017 High

    Demonstrating paracrine pleiotrophin–PTPRZ1 signaling sustains glioma stem cells and that PTPRZ1 inhibitors cross the blood-brain barrier opened a therapeutic axis.

    Evidence Macrophage/GSC co-implantation, PTN/PTPRZ1 shRNA and antibody blockade, in vivo tumor assays; small-molecule phosphatase inhibitors with IC50 ~0.1 μM

    PMID:28569747 PMID:29275231

    Open questions at the time
    • Direct phosphatase substrates downstream of GSC maintenance unmapped
    • Inhibitor specificity beyond PTPRZ1 not fully characterized
  11. 2019 High

    Genetic and structural work established that RPTPζ–tenascin-R protein-protein interactions are required for reticulated perineuronal net assembly, defining a non-catalytic structural role.

    Evidence Ptprz1 knockout mice, structural determination and interface mutagenesis with PNN assembly assays

    PMID:31822561 PMID:37356715

    Open questions at the time
    • Relationship between PNN role and phosphatase signaling unclear
    • Physiological consequence of PNN loss not detailed here
  12. 2024 High

    Identifying RNF26 Y432 as a direct dephosphorylation substrate and mapping PTN/PTPRZ1/c-Met/mTORC1 signaling provided concrete catalytic and signaling mechanisms for PTPRZ1's pro-tumoral and metabolic functions.

    Evidence Mass spectrometry substrate identification, phospho-specific Western blot, proteasome and crizotinib/rapamycin pharmacology, knockout endothelial cells

    PMID:23170925 PMID:29753117 PMID:37260355 PMID:39409168 PMID:39443724

    Open questions at the time
    • Full substrate repertoire of the phosphatase remains incomplete
    • Tissue-specific substrate selection unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the catalytic (substrate dephosphorylation), adhesive (CAM/tenascin/PNN), and oncogenic-fusion functions of PTPRZ1 are integrated within a single cell, and which substrate dictates each phenotype, remains unresolved.
  • No unified structural model linking ectodomain ligand binding to intracellular catalysis
  • Direct substrate catalogue still partial
  • Isoform-specific functions not systematically separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 3 GO:0001618 virus receptor activity 2 GO:0008092 cytoskeletal protein binding 2 GO:0016787 hydrolase activity 2 GO:0060089 molecular transducer activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 3 GO:0031012 extracellular matrix 3
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1474244 Extracellular matrix organization 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3
Partners
CNTN2ERBB4METNCAM1PTNRNF26TNCTNR
Complex memberships
ERBB4-MAGI-RPTPβ complexPTPRZ1-MET (ZM) fusion proteinperineuronal net

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Phosphacan (PTPRZ1 extracellular domain) is an alternatively spliced secreted variant of the transmembrane receptor-type protein tyrosine phosphatase RPTPζ/β, representing the entire extracellular portion of the receptor without transmembrane or intracellular phosphatase domains. cDNA cloning, amino acid sequencing, RNA analysis with domain-specific probes Proceedings of the National Academy of Sciences of the United States of America High 7511813
1994 Phosphacan binds with high affinity (Kd ~0.1 nM) to neural cell adhesion molecules N-CAM and Ng-CAM/L1, and inhibits neuronal adhesion and neurite growth; chondroitin sulfate accounts for only ~15% of binding, indicating the core glycoprotein mediates most of this interaction. Radioligand binding assay (125I-phosphacan), Scatchard analysis, chondroitinase treatment, anti-CAM antibody inhibition, neuronal adhesion and neurite outgrowth assays The Journal of cell biology High 7528221
1994 Phosphacan and neurocan bind with high affinity to tenascin-C (but not laminin or fibronectin), mediated via their core glycoproteins rather than chondroitin sulfate chains; phosphacan inhibits C6 glioma cell adhesion to tenascin-C. Fluorescent microbead co-aggregation, solid-phase radioligand binding assay, Scatchard analysis, chondroitinase treatment, cell adhesion assay The Journal of biological chemistry High 7512960
1995 Phosphacan interactions with N-CAM, Ng-CAM/L1, and tenascin are mediated by asparagine-linked complex-type oligosaccharides located in the carbonic anhydrase-like and fibronectin type III-like domains (at Asn-232 and Asn-381); peptide-N-glycosidase treatment reduced binding by 65–75%. 125I-phosphacan tryptic digest binding assays, peptide N-glycosidase F treatment, endo-β-N-acetylglucosaminidase H treatment, glycopeptide isolation and sequencing The Journal of biological chemistry High 7559574
1996 Phosphacan/6B4 proteoglycan binds pleiotrophin (HB-GAM) with high affinity (Kd = 0.25 nM and 3 nM for two sites); chondroitin sulfate chains modulate binding affinity; anti-6B4 antibody suppresses pleiotrophin-induced neurite outgrowth from cortical neurons, indicating this interaction is required for pleiotrophin's biological action. Affinity chromatography, N-terminal sequencing, Scatchard analysis of binding, chondroitinase ABC treatment, heparin competition, antibody-blocking neurite outgrowth assay The Journal of biological chemistry High 8702927
1996 TAG-1/axonin-1 is a high-affinity ligand of phosphacan (Kd ~0.04 nM); chondroitin sulfate chains account for ~70% of the binding to TAG-1, contrasting with phosphacan's N-CAM/Ng-CAM interactions which are N-glycan-mediated. Radioligand binding assay, Scatchard analysis, chondroitinase treatment, N-deglycosylation, immunocytochemistry The Journal of biological chemistry High 8663515
1996 Adsorbed phosphacan/6B4 proteoglycan acts as a repulsive substrate for cortical and thalamic neuronal adhesion, but in sparse culture conditions promotes neurite outgrowth and tyrosine phosphorylation of an 85 kDa protein in cortical neurons; chondroitinase or keratanase digestion did not affect this neurite-promoting activity, indicating the protein moiety is responsible. Patterned substrate cell adhesion assay, neurite outgrowth quantification, chondroitinase/keratanase digestion, antibody blocking, anti-phosphotyrosine Western blot Development (Cambridge, England) High 8625816
1997 Phosphacan binds to the fibrinogen-like globe domain of tenascin-C (Kd ~12 nM), mediated by the core protein in a calcium-dependent manner; all deletion variants retaining the fibrinogen globe support phosphacan binding, while those lacking it do not. Recombinant tenascin-C deletion constructs, radioligand binding assay, chondroitinase treatment, rotary shadowing electron microscopy, cell adhesion inhibition assay The Journal of biological chemistry High 9182584
1998 Phosphacan binds with high affinity to tenascin-R (Kd 2–7 nM) via its core protein; chondroitinase treatment increases binding by ~60%, indicating the glycosaminoglycan chains partially shield the protein-protein interaction site. Phosphacan also binds HB-GAM and amphoterin (Kd 0.3–8 nM) primarily through its chondroitin sulfate chains (>80% of binding). Radioligand binding assay, Scatchard analysis, chondroitinase treatment, calcium chelation experiments, immunocytochemistry The Journal of biological chemistry High 9507007
1998 The core protein of phosphacan binds FGF-2 with high affinity (Kd ~6 nM) primarily via the protein backbone (only ~35% reduction after chondroitinase treatment), and potentiates FGF-2 mitogenic activity on NIH/3T3 cells by 75–90%. Radioligand binding assay, chondroitinase treatment, [3H]-thymidine mitogenic assay on NIH/3T3 cells, immunocytochemistry The Journal of biological chemistry High 9705269
2003 The heterogeneity of chondroitin sulfate chains on phosphacan regulates its binding affinity for pleiotrophin; the presence of the GlcA(2S)-GalNAc(6S) disaccharide (D unit) in postnatal day 20 phosphacan confers ~5-fold stronger binding (Kd = 0.14 nM) compared with earlier preparations lacking this unit (Kd ~1.4–1.6 nM). Phosphacan purification from different developmental stages, surface plasmon resonance biosensor binding analysis, chondroitinase ABC digestion, disaccharide composition analysis, monoclonal antibody immunoreactivity The Journal of biological chemistry High 12840014
2003 Phosphacan short isoform (PSI), a novel truncated secreted variant encoded by a distinct cDNA, interacts with Ig cell adhesion molecules F3/contactin and L1, and promotes neurite outgrowth of cortical neurons as a coated substrate; PSI is not a proteoglycan but carries HNK-1 oligosaccharides. cDNA library screening, Northern blot, Western blot, co-immunoprecipitation/pulldown binding, neurite outgrowth assay The Journal of biological chemistry Medium 12700241
2007 PTPRZ1 (RPTPβ/ζ) forms a functional complex with ERBB4 via MAGI scaffolding proteins; ERBB4 expression leads to tyrosine phosphorylation of MAGI proteins (enhanced by neuregulin), and simultaneous binding of MAGI to RPTPβ creates a phosphotyrosine kinase/phosphatase complex with spatial and functional association confirmed in cultured cells. Yeast two-hybrid, co-immunoprecipitation in mammalian cells, tyrosine phosphorylation assays, neuregulin stimulation, spatial co-localization imaging Molecular psychiatry Medium 17579610
2007 PTPRZ1 overexpression activates the beta-catenin pathway in renal cell carcinoma via dephosphorylation-dependent nuclear translocation of beta-catenin, leading to expression of cyclin D1, c-myc, c-jun, fra-1, and CD44; siRNA knockdown of ptprz1 decreases nuclear beta-catenin and suppresses cellular proliferation. Gene expression microarray, CGH array, siRNA knockdown, Western blot for dephosphorylated/nuclear beta-catenin, proliferation assay The American journal of pathology Medium 18055543
2008 Egr-1 transcription factor directly binds the phosphacan promoter and transactivates its expression; Egr-1-deficient mice have lower phosphacan RNA and protein levels after stroke, establishing Egr-1 as a transcriptional regulator of PTPRZ1/phosphacan in reactive astrocytes. Promoter deletion/mutational analysis, chromatin immunoprecipitation, gain-of-function and loss-of-function in primary astrocytes, Egr-1 knockout mouse analysis The American journal of pathology High 18556777
2010 PTPRZ1 promoter is preferentially activated by HIF-2α over HIF-1α; ELK1 cooperates with HIF-2α to drive PTPRZ1 expression through nearby HRE and Ets binding sites; ELK1 knockdown reduces HIF-2-mediated activation by >50%, and ChIP confirms binding of both HIF and ELK1 to the PTPRZ1 promoter. Promoter deletion/mutational analysis, luciferase reporter assays, siRNA knockdown, chromatin immunoprecipitation (ChIP) PloS one High 20224786
2012 Binding of pleiotrophin ligand to PTPRZ1 activates PTN/PTPRZ1 signaling to induce tyrosine phosphorylation of calmodulin (CaM) in small-cell lung carcinoma cells; PTPRZ1 knockdown alters CaM phosphorylation and suppresses tumor progression in murine xenograft. shRNA-mediated knockdown, Western blot for tyrosine-phosphorylated CaM, in vivo xenograft tumor assay BMC cancer Medium 23170925
2012 RPTPζ/phosphacan undergoes abnormal O-mannosyl glycosylation in POMGnT1-knockout mice (a muscle-eye-brain disease model); loss of POMGnT1 shifts RPTPζ/phosphacan to lower molecular weight and eliminates HNK-1 carbohydrate epitopes, identifying RPTPζ/phosphacan as a significant substrate for O-mannosylation in the brain. POMGnT1 knockout mouse model, Western blot, immunofluorescence, lectin/antibody glycan epitope analysis Neuroscience Medium 22728091
2013 Phosphacan is the major carrier of O-mannose-linked HNK-1 glycan in developing mouse brain; GlcAT-P synthesizes the O-linked HNK-1 onto phosphacan, and the 6B4 monoclonal antibody preferentially recognizes O-mannose-linked HNK-1 on phosphacan. Mass spectrometry glycan identification, GlcAT-P and POMGnT1 knockout mice, cell expression with GlcAT-P co-transfection, immunoblotting Glycobiology High 24352591
2014 Phosphacan/RPTPβ is the major carrier of the Lewis X glycan epitope in the developing mouse brain; this epitope is carried on O-mannose-linked glycans, requires β4GalT2 for synthesis, and is abolished by POMGnT1 knockout. β4GalT2 and POMGnT1 knockout mice, immunochemical analysis, glycan structural characterization Glycobiology Medium 25361541
2014 PTPRZ1-MET (ZM) fusion proteins arise from chromosomal translocation fusing PTPRZ1 introns 3 or 8 to MET intron 1; exogenous expression of ZM fusion in U87MG glioblastoma cells enhances cell migration and invasion. RNA-seq, genomic translocation analysis, RT-PCR validation, exogenous overexpression in glioblastoma cell lines with migration/invasion assays Genome research High 25135958
2015 ZM fusion proteins retain MET processing and dimerization properties of wild-type MET, and enhance MET phosphorylation in both HGF-dependent and HGF-independent manners; fusion with PTPRZ1 increases MET mRNA expression levels. Western blot for MET phosphorylation/expression, HGF stimulation/withdrawal experiments, dimerization assays FEBS letters Medium 25935522
2015 O-mannosyl glycan epitopes recognized by antibodies Cat-315 and 3F8 define biochemically distinct glycoforms of RPTPζ/phosphacan that differentially decorate distinct neural cell populations; mass spectrometry characterization identified novel O-mannose-linked glycan structures including sulfo-N-acetyllactosamine modifications on RPTPζ/phosphacan. Multidimensional mass spectrometry of O-linked glycans from purified RPTPζ/phosphacan, cell-type-specific immunofluorescence with glycoform-specific antibodies The Journal of biological chemistry High 25737452
2017 Tumor-associated macrophages secrete pleiotrophin (PTN) which signals through its receptor PTPRZ1 on glioma stem cells (GSCs) to promote GSC maintenance and GBM tumor growth via paracrine PTN-PTPRZ1 signaling; disrupting PTPRZ1 abrogates GSC maintenance and tumorigenic potential, and anti-PTPRZ1 antibody suppresses tumor growth. Co-implantation of macrophages with GSCs, PTN shRNA silencing in macrophages, PTPRZ1 shRNA and antibody blockade, tumor growth and animal survival assays, in vivo xenograft Nature communications High 28569747
2017 Small-molecule inhibitors targeting the intracellular PD1 phosphatase domain of PTPRZ1 inhibit its tyrosine phosphatase activity (IC50 ~0.1 μM), increase phosphorylation of PTPRZ1 substrates involved in neuronal survival/differentiation, and the lead compound crosses the blood-brain barrier in vivo. In vitro phosphatase activity assay, docking/molecular dynamics, substrate phosphorylation Western blot, BBB permeability in vivo experiment European journal of medicinal chemistry Medium 29275231
2018 CDKN1A is the upstream regulator of PTN/PTPRZ1 expression in TNBC cells receiving chemotherapy; chemotherapy-driven increases in CDKN1A elevate PTN and PTPRZ1 expression, and the CDKN1A/PTN/PTPRZ1 axis promotes chemoresistance via the NF-κB pathway; siRNA knockdown of PTPRZ1 reduces chemoresistance. siRNA knockdown, microarray expression analysis, CCK-8 proliferation assay, colony formation, apoptosis analysis, NF-κB pathway western blot Cell communication and signaling : CCS Medium 30497491
2018 PTPRZ1 (RPTPβ/ζ) modulates ethanol signaling: ethanol increases phosphorylation of ALK and TrkA (known PTPRZ1 substrates) in neuroblastoma cells; PTPRZ1 small-molecule inhibitors also increase pALK and pTrkA but prevent ethanol-induced increases when co-applied, demonstrating PTPRZ1 modulates TrkA and ALK signaling pathways activated by alcohol. Pharmacological inhibitors (MY10, MY33-3), Western blot for pALK/pTrkA, behavioral tests in mice (binge drinking, conditioned place preference) Neuropharmacology Medium 29753117
2019 RPTPζ (PTPRZ1) is required for the reticulated perineuronal net (PNN) structure in the brain; Ptprz1 knockout mice lose the normal reticular PNN pattern (replaced by puncta), phenocopying tenascin-R knockout PNN defects. Two distinct surface interactions underpin PNN formation: one dependent on RPTPζ and another requiring hyaluronan. Ptprz1 knockout mice, immunofluorescence of PNN structure, biochemical fractionation, neuronal cultures The Journal of biological chemistry High 31822561
2021 ZM fusion proteins activate MET kinase in a ligand-independent manner, likely enabled by a coiled-coil motif from the PTPRZ1 fusion segment that promotes constitutive MET dimerization/activation; clinical specimens confirm hyperactivation of MET signaling in ZM-positive gliomas. Protein structure prediction, cell line MET phosphorylation assays with/without HGF, clinical specimen MET signaling analysis, high-sensitivity RT-PCR CNS neuroscience & therapeutics Medium 33645009
2022 Phosphacan exerts repulsive effects on cerebellar granule cell migration through interaction with TAG-1; the interaction is mediated by chondroitin sulfate C chains (confirmed by SPR), requires GD3 ganglioside-containing lipid rafts, and attenuates BDNF-induced Akt activation and migration. TAG-1 knockout mouse primary cerebellar granule cells, Boyden chamber migration assay, surface plasmon resonance for TAG-1/CS-C binding, anti-GD3/GD1b antibody blocking, methyl-β-cyclodextrin lipid raft disruption, Akt inhibitor MK-2206 Journal of neurochemistry High 36227633
2022 HOXA5 directly binds the PTPRZ1 promoter to transcriptionally activate PTPRZ1 expression in glioblastoma stem cells; suppression of PTPRZ1 largely reverses the pro-tumoral effects of HOXA5 overexpression, placing PTPRZ1 downstream of HOXA5 in a GSC maintenance pathway. ChIP for HOXA5 binding to PTPRZ1 promoter, HOXA5 gain/loss-of-function, PTPRZ1 knockdown, GSC self-renewal and invasion assays, in vivo tumor propagation Cancer letters Medium 35219772
2023 Tenascin-R (TNR) directly associates with the RPTPζ ectodomain via protein-protein interactions; the same interface mediates RPTPζ interaction with tenascin-C; mutating RPTPζ residues at the RPTPζ-TNR interface impairs PNN formation in dissociated neuronal cultures, demonstrating these protein-protein interactions are structurally required for PNN assembly. Structural determination of RPTPζ-TNR interaction, mutagenesis of interface residues, neuronal culture PNN assembly assay, Ptprz1 knockout mouse The Journal of biological chemistry High 37356715
2023 Loss of PTPRZ1 tyrosine phosphatase activity in endothelial cells (genetic knockout or pharmacological inhibition) activates c-Met and Akt, reduces β3 integrin expression, and enhances angiogenesis and lung adenocarcinoma growth in vivo; PTN and VEGFA165 activate c-Met and Akt in a PTPRZ1-dependent manner, and these effects are abolished by the c-Met inhibitor crizotinib. Ptprz1−/− and Ptprz1+/+ mouse endothelial cells, in vivo urethane-induced LUAD model, PTPRZ1 inhibitor, Western blot for c-Met/Akt/VEGFR2/β3 integrin, crizotinib blockade International journal of cancer Medium 37260355
2024 PTPRZ1 dephosphorylates RNF26 at the Y432 site, thereby stabilizing RNF26 protein expression through the proteasome pathway; through this PTPRZ1-RNF26 interaction, PTPRZ1 activates the TNF/NF-κB signaling pathway to promote cell proliferation, angiogenesis, and lipid metabolism in clear cell renal cell carcinoma. Mass spectrometry substrate identification, RNA sequencing, lipidomic profiling, immunohistochemistry, phospho-specific Western blot, proteasome inhibitor experiments, RNF26 knockdown rescue Oncogene High 39443724
2025 Curcumin interacts with PTPRZ1 to maintain its enzymatic (phosphatase) activity, thereby regulating phosphorylation of the m6A-reader YTHDF2; this modulation of YTHDF2 phosphorylation via PTPRZ1 affects downstream gene expression to reduce microglial inflammatory responses. Binding/interaction assays between curcumin and PTPRZ1, phosphorylation assays for YTHDF2, gene expression analysis Advanced science (Weinheim, Baden-Wurttemberg, Germany) Low 39921492
2024 ZM (PTPRZ1-MET) fusion-positive glioma stem cells upregulate ISG20 through the MET-STAT3-ISG20 signaling axis; secreted ISG20 recruits macrophages and drives their polarization toward an immunosuppressive M2-like phenotype, promoting tumor progression. RNA-seq of patient glioma tissues, ZM overexpression/knockdown, STAT3 inhibition, ISG20 knockdown, macrophage co-culture polarization assays Cellular signalling Medium 38685521
2024 PTN activates c-Met and mTORC1-dependent protein synthesis through PTPRZ1; PTPRZ1 deletion or PTN stimulation increases phosphorylation of S6K1 and 4EBP1 (mTORC1 substrates) and upregulates HIF-1α; c-Met inhibitor crizotinib abolishes these effects, placing c-Met downstream of the PTN/PTPRZ1 axis upstream of mTORC1 in endothelial cell migration. Ptprz1 knockout endothelial cells, PTN stimulation, Western blot for mTORC1 substrates (pS6K1, p4EBP1), crizotinib and rapamycin pharmacological blockade, cell migration assays International journal of molecular sciences Medium 39409168
2022 PTPRZ1 overexpression regulates phosphorylation of p120 and β-catenin, causing their redistribution from cell membrane to cytoplasm and nucleus, activating downstream targets (RhoA, Rac1, CDC42, cyclin D1, c-myc) and promoting cell proliferation, migration, and invasion in oral submucous fibrosis; PTPRZ1 knockdown reduces tumor volume in vivo. PTPRZ1 overexpression/knockdown, Western blot and immunofluorescence for p-p120/p-β-catenin localization, cell migration/invasion assays, in vivo tumor formation Journal of oncology Medium 35251170
2024 Integrin α6β4 regulates PTPRZ1 expression through a UCHL1-Hif-1α axis: integrin α6β4 upregulates UCHL1, which stabilizes Hif-1α nuclear localization, leading to transcriptional activation of PTPRZ1; inhibition of UCHL1 or PTPRZ1 dramatically decreases integrin α6β4-mediated cell migration and 3D invasive growth in TNBC. ITGB4 re-expression and KO, shRNA knockdown, chemical Hif-1α inhibition/activation, UCHL1 inhibition, migration and 3D invasion assays Cancers Medium 39518121

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury. Experimental neurology 425 12895450
1999 The chondroitin sulfate proteoglycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar. The Journal of neuroscience : the official journal of the Society for Neuroscience 376 10594061
2014 RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas. Genome research 334 25135958
1994 Interactions of the chondroitin sulfate proteoglycan phosphacan, the extracellular domain of a receptor-type protein tyrosine phosphatase, with neurons, glia, and neural cell adhesion molecules. The Journal of cell biology 299 7528221
2017 Tumour-associated macrophages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth. Nature communications 289 28569747
1994 Phosphacan, a chondroitin sulfate proteoglycan of brain that interacts with neurons and neural cell-adhesion molecules, is an extracellular variant of a receptor-type protein tyrosine phosphatase. Proceedings of the National Academy of Sciences of the United States of America 286 7511813
1996 6B4 proteoglycan/phosphacan, an extracellular variant of receptor-like protein-tyrosine phosphatase zeta/RPTPbeta, binds pleiotrophin/heparin-binding growth-associated molecule (HB-GAM). The Journal of biological chemistry 263 8702927
1994 Interactions with tenascin and differential effects on cell adhesion of neurocan and phosphacan, two major chondroitin sulfate proteoglycans of nervous tissue. The Journal of biological chemistry 231 7512960
1996 TAG-1/axonin-1 is a high-affinity ligand of neurocan, phosphacan/protein-tyrosine phosphatase-zeta/beta, and N-CAM. The Journal of biological chemistry 182 8663515
1998 High affinity binding and overlapping localization of neurocan and phosphacan/protein-tyrosine phosphatase-zeta/beta with tenascin-R, amphoterin, and the heparin-binding growth-associated molecule. The Journal of biological chemistry 168 9507007
1999 DSD-1-proteoglycan is the mouse homolog of phosphacan and displays opposing effects on neurite outgrowth dependent on neuronal lineage. The Journal of neuroscience : the official journal of the Society for Neuroscience 159 10234020
2004 Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries. The European journal of neuroscience 155 15016081
1996 Neurocan and phosphacan: two major nervous tissue-specific chondroitin sulfate proteoglycans. Perspectives on developmental neurobiology 144 9117260
1996 Chondroitin sulfate proteoglycans in the developing central nervous system. II. Immunocytochemical localization of neurocan and phosphacan. The Journal of comparative neurology 134 8866845
1995 Purification, characterization and developmental expression of a brain-specific chondroitin sulfate proteoglycan, 6B4 proteoglycan/phosphacan. Neuroscience 124 7477903
1995 Chondroitin sulfate and chondroitin/keratan sulfate proteoglycans of nervous tissue: developmental changes of neurocan and phosphacan. Journal of neurochemistry 116 7595522
1996 Chondroitin sulfate proteoglycans in the developing central nervous system. I. cellular sites of synthesis of neurocan and phosphacan. The Journal of comparative neurology 108 8866844
2017 Tumour exosomes from cells harbouring PTPRZ1-MET fusion contribute to a malignant phenotype and temozolomide chemoresistance in glioblastoma. Oncogene 107 28504721
1996 6B4 proteoglycan/phosphacan is a repulsive substratum but promotes morphological differentiation of cortical neurons. Development (Cambridge, England) 105 8625816
2001 Inhibitory effects of neurocan and phosphacan on neurite outgrowth from retinal ganglion cells in culture. Investigative ophthalmology & visual science 95 11431463
1997 The fibrinogen-like globe of tenascin-C mediates its interactions with neurocan and phosphacan/protein-tyrosine phosphatase-zeta/beta. The Journal of biological chemistry 91 9182584
2003 Heterogeneity of the chondroitin sulfate portion of phosphacan/6B4 proteoglycan regulates its binding affinity for pleiotrophin/heparin binding growth-associated molecule. The Journal of biological chemistry 89 12840014
1996 Comparison of RPTP zeta/beta, phosphacan, and trkB mRNA expression in the developing and adult rat nervous system and induction of RPTP zeta/beta and phosphacan mRNA following brain injury. Brain research. Molecular brain research 88 8840016
2003 Phosphacan short isoform, a novel non-proteoglycan variant of phosphacan/receptor protein tyrosine phosphatase-beta, interacts with neuronal receptors and promotes neurite outgrowth. The Journal of biological chemistry 82 12700241
1998 The core protein of the chondroitin sulfate proteoglycan phosphacan is a high-affinity ligand of fibroblast growth factor-2 and potentiates its mitogenic activity. The Journal of biological chemistry 82 9705269
1996 Expression of polypeptide variants of receptor-type protein tyrosine phosphatase beta: the secreted form, phosphacan, increases dramatically during embryonic development and modulates glial cell behavior in vitro. Journal of neuroscience research 78 8984199
2003 Regulation of RPTPbeta/phosphacan expression and glycosaminoglycan epitopes in injured brain and cytokine-treated glia. Molecular and cellular neurosciences 75 14697661
2009 NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury. BMC neurology 72 19604403
2007 Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene. Molecular psychiatry 72 17579610
1997 Isolation of a tenascin-R binding protein from mouse brain membranes. A phosphacan-related chondroitin sulfate proteoglycan. The Journal of biological chemistry 69 9405406
2006 Monoclonal antibody Cat-315 detects a glycoform of receptor protein tyrosine phosphatase beta/phosphacan early in CNS development that localizes to extrasynaptic sites prior to synapse formation. Neuroscience 66 16989954
2006 DSD-1-Proteoglycan/Phosphacan and receptor protein tyrosine phosphatase-beta isoforms during development and regeneration of neural tissues. Advances in experimental medicine and biology 64 16955703
1995 Complex-type asparagine-linked oligosaccharides on phosphacan and protein-tyrosine phosphatase-zeta/beta mediate their binding to neural cell adhesion molecules and tenascin. The Journal of biological chemistry 64 7559574
2008 Egr-1 regulates expression of the glial scar component phosphacan in astrocytes after experimental stroke. The American journal of pathology 53 18556777
2001 Tenascin glycoproteins and the complementary ligand DSD-1-PG/ phosphacan--structuring the neural extracellular matrix during development and repair. Restorative neurology and neuroscience 51 12082229
2003 Phosphacan and neurocan are repulsive substrata for adhesion and neurite extension of adult rat dorsal root ganglion neurons in vitro. Experimental neurology 50 12821372
2003 Kainic acid-induced convulsions cause prolonged changes in the chondroitin sulfate proteoglycans neurocan and phosphacan in the limbic structures. Experimental neurology 49 14637091
1998 Coordinate expression of L1 and 6B4 proteoglycan/phosphacan is correlated with the migration of mesencephalic dopaminergic neurons in mice. Brain research. Developmental brain research 47 9593903
2007 Chronic oxidative stress causes amplification and overexpression of ptprz1 protein tyrosine phosphatase to activate beta-catenin pathway. The American journal of pathology 45 18055543
2019 The protein tyrosine phosphatase RPTPζ/phosphacan is critical for perineuronal net structure. The Journal of biological chemistry 40 31822561
2005 Neuronal expression of the chondroitin sulfate proteoglycans receptor-type protein-tyrosine phosphatase beta and phosphacan. Neuroscience 40 15708477
2018 Chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis promote chemoresistance by activating the NF-κB pathway in breast cancer cells. Cell communication and signaling : CCS 39 30497491
2013 Structural and biochemical characterization of O-mannose-linked human natural killer-1 glycan expressed on phosphacan in developing mouse brains. Glycobiology 39 24352591
2016 Early remodelling of the extracellular matrix proteins tenascin-C and phosphacan in retina and optic nerve of an experimental autoimmune glaucoma model. Journal of cellular and molecular medicine 37 27374750
2012 RPTPζ/phosphacan is abnormally glycosylated in a model of muscle-eye-brain disease lacking functional POMGnT1. Neuroscience 37 22728091
2001 Expression of brain specific chondroitin sulfate proteoglycans, neurocan and phosphacan, in the developing and adult hippocampus of Ihara's epileptic rats. Brain research 32 11292447
2017 Development of inhibitors of receptor protein tyrosine phosphatase β/ζ (PTPRZ1) as candidates for CNS disorders. European journal of medicinal chemistry 31 29275231
2015 Neurons and glia modify receptor protein-tyrosine phosphatase ζ (RPTPζ)/phosphacan with cell-specific O-mannosyl glycans in the developing brain. The Journal of biological chemistry 31 25737452
2004 Keratan sulfate proteoglycan phosphacan regulates mossy fiber outgrowth and regeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 14724244
2004 Activity-dependent regulation of a chondroitin sulfate proteoglycan 6B4 phosphacan/RPTPbeta in the hypothalamic supraoptic nucleus. Brain research 30 15261112
2012 PTPRZ1 regulates calmodulin phosphorylation and tumor progression in small-cell lung carcinoma. BMC cancer 29 23170925
2007 Differential expression of phosphacan/RPTPbeta isoforms in the developing mouse visual system. The Journal of comparative neurology 27 17722031
2015 Requirement of keratan sulfate proteoglycan phosphacan with a specific sulfation pattern for critical period plasticity in the visual cortex. Experimental neurology 26 26277687
2010 Characterization of the activation of protein tyrosine phosphatase, receptor-type, Z polypeptide 1 (PTPRZ1) by hypoxia inducible factor-2 alpha. PloS one 26 20224786
2023 Protein-protein interactions between tenascin-R and RPTPζ/phosphacan are critical to maintain the architecture of perineuronal nets. The Journal of biological chemistry 23 37356715
2000 Dynamic spatiotemporal expression patterns of neurocan and phosphacan indicate diverse roles in the developing and adult mouse olfactory system. The Journal of comparative neurology 23 10861539
1996 Cell surface-associated extracellular distribution of a neural proteoglycan, 6B4 proteoglycan/phosphacan, in the olfactory epithelium, olfactory nerve, and cells migrating along the olfactory nerve in chick embryos. Neuroscience research 22 8861104
2015 Enhanced expression and phosphorylation of the MET oncoprotein by glioma-specific PTPRZ1-MET fusions. FEBS letters 21 25935522
2014 Major glycan structure underlying expression of the Lewis X epitope in the developing brain is O-mannose-linked glycans on phosphacan/RPTPβ. Glycobiology 21 25361541
2018 Pharmacological inhibition of Receptor Protein Tyrosine Phosphatase β/ζ (PTPRZ1) modulates behavioral responses to ethanol. Neuropharmacology 20 29753117
2010 Glypican-1, phosphacan/receptor protein-tyrosine phosphatase-ζ/β and its ligand, tenascin-C, are expressed by neural stem cells and neural cells derived from embryonic stem cells. ASN neuro 20 20689858
2005 No association of FOXP2 and PTPRZ1 on 7q31 with autism from the Japanese population. Neuroscience research 20 15998549
2005 Chondroitin sulfate proteoglycan phosphacan associates with parallel fibers and modulates axonal extension and fasciculation of cerebellar granule cells. Molecular and cellular neurosciences 18 16150606
2000 Spatiotemporal expression patterns of 6B4 proteoglycan/phosphacan in the developing rat retina. Investigative ophthalmology & visual science 18 10845626
2025 Curcumin Modulates PTPRZ1 Activity and RNA m6A Modifications in Neuroinflammation-Associated Microglial Response. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 39921492
2022 HOXA5 is amplified in glioblastoma stem cells and promotes tumor progression by transcriptionally activating PTPRZ1. Cancer letters 17 35219772
2022 Targeted OUM1/PTPRZ1 silencing and synergetic CDT/enhanced chemical therapy toward uveal melanoma based on a dual-modal imaging-guided manganese metal-organic framework nanoparticles. Journal of nanobiotechnology 17 36335349
2010 Significance of PTPRZ1 and CIN85 expression in cervical carcinoma. Archives of gynecology and obstetrics 16 20882291
2004 Expression of phosphacan and neurocan during early development of mouse retinofugal pathway. Brain research. Developmental brain research 16 15283989
2011 Phosphacan and receptor protein tyrosine phosphatase β expression mediates deafferentation-induced synaptogenesis. Hippocampus 15 20014386
2007 Brevican and phosphacan expression and localization following transient middle cerebral artery occlusion in the rat. Biochemical Society transactions 15 17635124
2019 A novel PTPRZ1-ETV1 fusion in gliomas. Brain pathology (Zurich, Switzerland) 14 31381204
2005 Cortical neurons express PSI, a novel isoform of phosphacan/RPTPbeta. Cell and tissue research 14 16028071
2001 Developmentally regulated expression of brain-specific chondroitin sulfate proteoglycans, neurocan and phosphacan, in the postnatal rat hippocampus. Cell and tissue research 14 11702233
2023 PTPRZ1-METFUsion GENe (ZM-FUGEN) trial: study protocol for a multicentric, randomized, open-label phase II/III trial. Chinese neurosurgical journal 13 37443050
2021 High-sensitive clinical diagnostic method for PTPRZ1-MET and the characteristic protein structure contributing to ligand-independent MET activation. CNS neuroscience & therapeutics 13 33645009
2021 Recurrent PTPRZ1-MET fusion and a high occurrence rate of MET exon 14 skipping in brain metastases. Cancer science 12 34812554
2002 Chondroitin sulfate proteoglycan phosphacan/RPTPbeta in the hypothalamic magnocellular nuclei. Brain research 9 12213306
2024 PTPRZ1-Targeting RNA CAR T Cells Exert Antigen-Specific and Bystander Antitumor Activity in Glioblastoma. Cancer immunology research 8 39269445
2019 MiR-1261/circ-PTPRZ1/PAK1 pathway regulates glioma cell growth and invasion. Human cell 8 31364003
2019 L1 Cell Adhesion Molecule Overexpression Down Regulates Phosphacan and Up Regulates Structural Plasticity-Related Genes Rostral and Caudal to the Complete Spinal Cord Transection. Journal of neurotrauma 8 31426714
2024 The PTPRZ1-MET/STAT3/ISG20 axis in glioma stem-like cells modulates tumor-associated macrophage polarization. Cellular signalling 7 38685521
2024 Cell Fate Dynamics Reconstruction Identifies TPT1 and PTPRZ1 Feedback Loops as Master Regulators of Differentiation in Pediatric Glioblastoma-Immune Cell Networks. Interdisciplinary sciences, computational life sciences 7 39420135
2023 Genetic deletion or tyrosine phosphatase inhibition of PTPRZ1 activates c-Met to up-regulate angiogenesis and lung adenocarcinoma growth. International journal of cancer 7 37260355
2016 High PTPRQ Expression and Its Relationship to Expression of PTPRZ1 and the Presence of KRAS Mutations in Colorectal Cancer Tissues. Anticancer research 7 26851024
2014 Expression of the heparin-binding growth factor midkine and its receptor, Ptprz1, in adult rat pituitary. Cell and tissue research 7 25519047
2001 Recombinant core protein fragment of phosphacan, a brain specific chondroitin sulfate proteoglycan, promote excitotoxic cell death of cultured rat hippocampal neurons. Neuroscience letters 7 11343829
1997 Identification of monoclonal antibody At5 as a new member of HNK-1 antibody family: the reactivity with myelin-associated glycoprotein and with two brain-specific proteoglycans, phosphacan and neurocan. Neurochemical research 6 9016838
2022 Overexpression of PTPRZ1 Regulates p120/β-Catenin Phosphorylation to Promote Carcinogenesis of Oral Submucous Fibrosis. Journal of oncology 5 35251170
2008 No association between the protein tyrosine phosphatase, receptor-type, Z Polypeptide 1 (PTPRZ1) gene and schizophrenia in the Japanese population. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 5 18186075
2005 Tyrosine kinase A but not phosphacan/protein tyrosine phosphatase-zeta/beta immunoreactivity and protein level changes in neurons and astrocytes in the gerbil hippocampus proper after transient forebrain ischemia. Brain research 5 15725399
2026 Human organoid tumor transplantation identifies functional glioblastoma-microenvironment communication mediated by PTPRZ1. Cell reports 4 41543935
2022 Phosphacan acts as a repulsive cue in murine and rat cerebellar granule cells in a TAG-1/GD3 rafts-dependent manner. Journal of neurochemistry 4 36227633
2025 Enhancer Reprogramming Reveals the Tumorigenic Role of PTPRZ1 in Lung Squamous Cell Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 40899632
2024 Integrin α6β4 Upregulates PTPRZ1 Through UCHL1-Mediated Hif-1α Nuclear Accumulation to Promote Triple-Negative Breast Cancer Cell Invasive Properties. Cancers 3 39518121
2025 Regulation of Pleiotrophin and PTPRZ1 Expression by Hypoxia to Restrict Hypoxia-Induced Cell Migration. Cancers 2 40361445
2024 Pleiotrophin Activates cMet- and mTORC1-Dependent Protein Synthesis through PTPRZ1-The Role of ανβ3 Integrin. International journal of molecular sciences 2 39409168
2017 [Expression of PTPRZ1 in oral squamous cell carcinoma originated from oral submucous fibrosis and its clinical significance]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 2 28815252
2008 [Effects of androgen on phosphacan and NG2 proteoglycan expression and neurite regeneration in neonatal rats with hypoxic-ischemic brain damage]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 2 18554468
2024 PTPRZ1 dephosphorylates and stabilizes RNF26 to reduce the efficacy of TKIs and PD-1 blockade in ccRCC. Oncogene 1 39443724

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