Affinage

PTP4A1

Protein tyrosine phosphatase type IVA 1 · UniProt Q93096

Length
173 aa
Mass
19.8 kDa
Annotated
2026-04-28
79 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTP4A1 (PRL-1) is a prenylated dual-specificity phosphatase that integrates phosphoprotein and phospholipid signaling at the plasma membrane and early endosomes to regulate cell proliferation, migration, and metabolic homeostasis. It dephosphorylates protein substrates—cytohesin-2 at Tyr381 to control Schwann cell myelination (PMID:35077201) and USF1 at Ser309 to suppress NF-κB-driven vascular inflammation (PMID:36534975)—and also acts as a lipid phosphatase converting PI(3,4)P2 and PI(3,5)P2 to PI(3)P to promote macropinocytosis and membrane dynamics (PMID:38948056). PRL-1 additionally binds p115 RhoGAP via a non-canonical SH3 interaction to coordinately activate ERK1/2 and RhoA (PMID:22009749), interacts with SRC independently of phosphatase activity to drive TGFβ/ERK/SMAD3-mediated fibrosis (PMID:29057934), and engages the CBS-pair domain of CNNM magnesium transporters to modulate TRPM7-dependent intracellular Mg²⁺ and cellular bioenergetics (PMID:36972446, PMID:27899452). Its catalytic cysteine undergoes reversible oxidative inactivation via an intramolecular Cys104–Cys49 disulfide, and it functions as a membrane-associated trimer whose assembly, polybasic phosphoinositide-binding region, and C-terminal farnesylation are each required for biological activity (PMID:16142898, PMID:15571731, PMID:17656357).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    Identification of PRL-1 as a nuclear protein tyrosine phosphatase whose catalytic cysteine is essential for activity and whose overexpression induces a transformed phenotype established it as a growth-regulatory phosphatase.

    Evidence Active-site mutagenesis, in vitro phosphatase assay, stable transfection phenotypic readout in cultured cells

    PMID:8196618

    Open questions at the time
    • Physiological substrates unidentified
    • Nuclear versus cytoplasmic function unresolved
    • Mechanism of transformation unknown
  2. 2000 High

    Demonstrating that C-terminal CAAX farnesylation targets PRL-1 to the plasma membrane and early endosomes—not the nucleus—revised the understanding of its primary site of action.

    Evidence Farnesyltransferase inhibitor, prenylation-deficient mutants, EM immunogold labeling, subcellular fractionation

    PMID:10747914

    Open questions at the time
    • How prenylation cooperates with other membrane-targeting determinants unclear
    • Function at early endosomes versus plasma membrane not distinguished
  3. 2002 High

    Discovery of cell-cycle-dependent relocalization to centrosomes and the mitotic spindle, with catalytic and farnesylation mutants causing mitotic defects, linked PRL-1 to mitotic fidelity beyond simple growth regulation.

    Evidence Immunofluorescence of endogenous protein, conditional mutant expression, cell cycle analysis in HeLa cells

    PMID:12235145

    Open questions at the time
    • Mitotic substrate(s) unidentified
    • Whether mitotic function is direct or indirect unclear
  4. 2003 High

    Showing that PRL-1 overexpression promotes invasion and metastasis in mice in a phosphatase-activity-dependent manner established its oncogenic potential in vivo.

    Evidence Stable CHO cell expression with catalytically inactive mutant, in vivo mouse metastasis model

    PMID:12782572

    Open questions at the time
    • Signaling pathways mediating metastasis not yet identified
    • Relevance to endogenous expression levels unclear
  5. 2005 High

    Crystal structures revealed PRL-1 as a Cdc14-like dual-specificity phosphatase that forms a functionally important trimer and undergoes reversible oxidative inactivation via an intramolecular Cys104–Cys49 disulfide, establishing key regulatory mechanisms.

    Evidence X-ray crystallography (native and C104S mutant), biochemical kinetics, oxidation studies, subcellular fractionation confirming trimer in membrane fraction

    PMID:15571731 PMID:16142898

    Open questions at the time
    • In vivo conditions that trigger the oxidative switch not defined
    • Whether trimer disruption occurs physiologically unknown
  6. 2007 High

    Structure-function dissection showed that trimerization, catalytic activity, and a polybasic phosphoinositide-binding region are each independently required for PRL-1 biological function, tying oligomerization and membrane targeting to cellular outcome.

    Evidence Trimer-disrupting and polybasic-region mutants with proliferation/migration readouts, phosphoinositide-binding assays

    PMID:17656357

    Open questions at the time
    • Specific phosphoinositide species recognized in vivo not determined
    • How trimerization regulates substrate access unknown
  7. 2007 Medium

    Connecting PRL-1 to Src/FAK/ERK signaling and Rac1/Cdc42 activation in cancer cells began to define the downstream signaling architecture, though direct substrates remained elusive.

    Evidence Overexpression/knockdown, pharmacological inhibition of Src/ERK, GTPase activation assays in A549 and other cell lines

    PMID:17234774 PMID:19199380

    Open questions at the time
    • Direct substrate mediating Src activation not identified
    • Overexpression-based signaling may not reflect endogenous stoichiometry
  8. 2011 High

    Structural and biochemical demonstration that PRL-1 directly binds the SH3 domain of p115 RhoGAP via a non-canonical interface to simultaneously activate ERK1/2 and RhoA identified the first well-characterized direct binding partner with a clear dual-pathway mechanism.

    Evidence X-ray structure of PRL-1·SH3 peptide complex, in vitro pulldown, Co-IP, kinase/GAP activity assays

    PMID:22009749

    Open questions at the time
    • Whether p115 RhoGAP is a phosphatase substrate or only a binding partner unclear
    • Quantitative contribution to ERK/RhoA activation in vivo not assessed
  9. 2016 High

    Crystal structure of PRL-1 bound to the CNNM2 CBS-pair domain revealed a heterotetrameric complex and implicated PRL-1 in regulating magnesium transport, opening a new axis of PRL-1 function beyond classical phosphoprotein signaling.

    Evidence X-ray crystallography, interface mutagenesis

    PMID:27899452

    Open questions at the time
    • Functional consequence for Mg²⁺ transport not directly measured in this study
    • Whether PRL-1 dephosphorylates CNNM or acts as a pseudosubstrate unknown
  10. 2017 High

    Identification of a phosphatase-independent interaction between PTP4A1 and SRC that promotes TGFβ/ERK/SMAD3-driven fibrosis revealed a scaffolding function distinct from its catalytic role.

    Evidence Reciprocal Co-IP, phosphatase-dead mutant retaining SRC interaction, in vivo bleomycin fibrosis model

    PMID:29057934

    Open questions at the time
    • Structural basis of the PTP4A1–SRC interaction unknown
    • Whether the oxidized (inactive) form preferentially serves this scaffolding role in vivo not established
  11. 2022 High

    Identification of cytohesin-2 Tyr381 as a direct PTP4A1 substrate in Schwann cells, validated by knockin mouse, provided the first rigorously defined phosphosite-level substrate controlling a physiological process (myelination).

    Evidence Schwann cell-specific conditional knockdown, Y381F knockin mice, Arf6 activity assays, sciatic nerve histology

    PMID:35077201

    Open questions at the time
    • Whether cytohesin-2 dephosphorylation by PTP4A1 occurs in other cell types unknown
    • How PTP4A1 is recruited to cytohesin-2 mechanistically undefined
  12. 2023 High

    Demonstrating that PRL-1/2 counteract ARL15-mediated CNNM3–TRPM7 complex formation to enhance TRPM7 channel activity and intracellular Mg²⁺ completed the mechanistic link between PRL–CNNM binding and magnesium homeostasis, with consequences for mitochondrial bioenergetics.

    Evidence Genetically encoded Mg²⁺ reporter, reciprocal Co-IP, TRPM7 activity assays, mitochondrial function assays

    PMID:36972446

    Open questions at the time
    • Whether PRL-1 catalytic activity or mere binding drives CNNM–TRPM7 dissociation unclear
    • Relative contributions of PRL-1 vs PRL-2 to Mg²⁺ regulation not resolved
  13. 2023 High

    Identification of USF1 Ser309 as a PTP4A1 substrate that drives A20/TNFAIP3 expression and NF-κB suppression, validated in knockout and transgenic mice with atherosclerosis phenotypes, established an anti-inflammatory vascular function.

    Evidence Site-specific phosphorylation analysis, ChIP, luciferase reporter, Ptp4a1 KO and transgenic mice, in vivo atherosclerosis model

    PMID:36534975

    Open questions at the time
    • How a tyrosine phosphatase dephosphorylates a serine residue mechanistically not addressed
    • Whether this pathway operates outside endothelial cells unknown
  14. 2024 Medium

    Demonstration that PRL-1 functions as a lipid phosphatase converting PI(3,4)P2 and PI(3,5)P2 to PI(3)P expanded its substrate repertoire beyond phosphoproteins to phosphoinositides, linking it to macropinocytosis and nutrient uptake.

    Evidence Biochemical phosphoinositide substrate assays, membrane ruffle/bleb imaging, macropinocytosis assays

    PMID:38948056

    Open questions at the time
    • Single study; independent replication needed
    • Relative contribution of lipid vs protein phosphatase activity to oncogenic phenotypes unclear
  15. 2025 High

    Trapping and solving the crystal structure of the phosphocysteine catalytic intermediate showed that phosphocysteine sterically blocks CNNM binding and that the general acid Asp72 plays an opposite catalytic role compared to classical PTPs, revealing unique mechanistic features of the PRL family.

    Evidence X-ray crystallography of C49S/D72A phosphocysteine intermediate, comparative kinetic assays across PRL paralogs and classical PTPs

    PMID:40398601

    Open questions at the time
    • Physiological lifetime of the phosphocysteine intermediate in cells unknown
    • Whether CNNM exclusion by phosphocysteine constitutes a regulatory switch in vivo not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PTP4A1 selects among its diverse protein and lipid substrates in different cellular contexts—and the relative contributions of catalytic versus scaffolding functions to each physiological outcome—remains unresolved.
  • No structural basis for substrate selectivity among protein/lipid substrates
  • Context-dependent regulation of the oxidative switch in vivo not mapped
  • Quantitative contribution of trimerization to substrate channeling unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016787 hydrolase activity 3 GO:0008289 lipid binding 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005768 endosome 1 GO:0005783 endoplasmic reticulum 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1430728 Metabolism 2 R-HSA-382551 Transport of small molecules 2 R-HSA-1640170 Cell Cycle 1 R-HSA-168256 Immune System 1
Partners
ARHGAP35CNNM2CNNM3CYTH2PKMPTENSRCUSF1
Complex memberships
PRL-1 homotrimerPRL-1–CNNM2 heterotetramer

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 PRL-1 (PTP4A1) encodes a 20-kDa protein tyrosine phosphatase capable of dephosphorylating phosphotyrosine substrates; mutation of the active-site cysteine abolishes phosphatase activity. PRL-1 is located primarily in the cell nucleus, and stable overexpression causes altered cellular growth, morphology, and a transformed phenotype. Active-site mutagenesis, in vitro phosphatase assay, immunofluorescence, stable transfection with phenotypic readout Molecular and cellular biology High 8196618
2000 PRL-1, -2, and -3 are prenylated at their C-terminal CAAX motif; prenylation is required for their primary association with the plasma membrane and early endosomal compartment. Inhibition of farnesyltransferase (FTI-277) or deletion of the prenylation signal causes nuclear relocalization of PRL-1. Farnesyltransferase inhibitor treatment, prenylation-deficient mutants, electron microscope immunogold labeling, brefeldin A/wortmannin treatment, subcellular fractionation The Journal of biological chemistry High 10747914
2002 PRL-1 exhibits cell cycle-dependent subcellular localization: in non-mitotic HeLa cells it localizes to the endoplasmic reticulum in a farnesylation-dependent manner; in mitotic cells it relocalizes to centrosomes and the spindle apparatus in a farnesylation-independent manner. Expression of a catalytic-domain mutant delays mitotic progression, and a farnesylation-site mutant causes chromosomal bridges and lagging chromosomes without affecting spindle checkpoint function. Immunofluorescence of endogenous protein, conditional expression of catalytic/farnesylation mutants, cell cycle analysis The Journal of biological chemistry High 12235145
2003 PRL-1 (and PRL-3) promote cell motility, invasive activity, and metastasis in vivo; catalytically inactive PRL-3 mutant shows significantly reduced migration-promoting activity, indicating the phosphatase activity is required. PRL-1/3-expressing CHO cells form metastatic tumors in mice. Stable CHO cell expression, catalytically inactive mutant, migration/invasion assays, in vivo mouse metastasis model Cancer research High 12782572
2005 Crystal structure of PRL-1 reveals it is a dual-specificity phosphatase most similar to Cdc14; it forms a trimer in the crystalline state burying ~1140 Ų per dimer interface. Trimerization creates a membrane-binding surface combining C-terminal basic residues with the prenylation group. Native PRL-1 crystallizes in an oxidized form with a disulfide between active-site Cys104 and neighboring Cys49, blocking substrate binding and catalysis; biochemical studies in solution and in cells support a regulatory role for this intramolecular disulfide in response to H2O2. X-ray crystallography (native and C104S mutant), biochemical kinetic analyses, oxidation studies in cell lysates Biochemistry High 16142898
2005 Crystal structure of human PRL-1 at 2.7 Å confirms trimeric assembly in the crystal; the trimer is also detected in the membrane fraction of cells, supporting biological relevance of oligomerization for PRL-1 activity regulation. X-ray crystallography, subcellular fractionation (membrane fraction immunoblot) Journal of molecular biology High 15571731
2001 PRL-1 physically interacts with the bZIP transcription factor ATF-7 via its phosphatase domain (interacting with ATF-7's bZIP region); PRL-1 can dephosphorylate ATF-7 in vitro, identifying ATF-7 as a substrate. Yeast two-hybrid, domain mapping, in vitro dephosphorylation assay The Journal of biological chemistry Medium 11278933
2007 PRL-1 promotes cell migration and invasion by activating Src kinase (increased Tyr416 phosphorylation), leading to phosphorylation of focal adhesion kinase (FAK) and p130Cas, and ERK1/2 activation. MMP2 and MMP9 levels are increased downstream of PRL-1 through AP1 and Sp1 transcription factors; MMP2/MMP9 knockdown or inhibition blocks PRL-1-mediated migration. Src and ERK1/2 activities are required for PRL-1-induced MMP upregulation. Stable overexpression, siRNA knockdown, pharmacological inhibition, western blotting for pathway components, migration/invasion assays Biochemistry Medium 19199380
2007 Knockdown of PRL-1 in human A549 lung cancer cells decreases c-Src and p130Cas expression and reduces Rac1 and Cdc42 activation, implicating PRL-1 in regulating cell adhesion and migration through these GTPases. Stable shRNA knockdown, western blot, GTPase activation assays, immunofluorescence Cancer research Medium 17234774
2007 PRL-1 phosphatase activity, trimerization, and the C-terminal polybasic region are each individually required for PRL-1-mediated cell proliferation and migration. The polybasic region mediates specific phosphoinositide recognition; both polybasic residues and the adjacent prenylation motif are required for proper subcellular localization and full biological activity. Cell-based overexpression/knockdown, trimer-disrupting and polybasic-region mutants, phosphoinositide-binding assays, migration/proliferation assays The Journal of biological chemistry High 17656357
2008 PRL-1 overexpression reduces p53 protein levels via two independent pathways: induction of PIRH2 transcription and induction of MDM2 phosphorylation through Akt signaling, both leading to p53 ubiquitination and proteasomal degradation. Conversely, siRNA ablation of PRL-1 increases p53 levels. PRL-1 transcription is regulated by p53 via a response element in its first intron, forming a negative feedback loop. Overexpression, siRNA knockdown, ubiquitination assays, Akt inhibition, luciferase reporter (p53-RE) Oncogene Medium 18997816
2011 PRL-1 directly binds the SH3 domain of p115 RhoGAP in vitro and in cells via a non-canonical interaction in which the PxxP ligand-binding site of the p115 RhoGAP SH3 domain occupies a groove in PRL-1. This prevents the canonical SH3–MEKK1 interaction, resulting in ERK1/2 activation; PRL-1 binding also inhibits the RhoGAP catalytic activity, leading to RhoA activation. In vitro pulldown, Co-IP in cells, X-ray structure of PRL-1·peptide complex, kinase/GAP activity assays The Journal of biological chemistry High 22009749
2016 Crystal structure of PRL-1 in complex with the Bateman module (CBS domains) of the magnesium transporter CNNM2 reveals a heterotetrameric assembly: a disc-like CNNM2BAT homodimer bound to two independent PRL-1 molecules at opposite tips. The interaction occurs via the catalytic domain of PRL-1, with Asp-558 in the CBS2 loop of CNNM2 critical for the association. PRL-1 binding to CNNM2 is proposed to increase intracellular Mg²⁺ and promote oncogenic transformation. X-ray crystallography, mutagenesis of key interface residues The Journal of biological chemistry High 27899452
2016 PRL1 (PTP4A1) knockout mice are fertile and show normal spermatogenesis, but combined PRL1/PRL2 reduction causes testicular atrophy and complete infertility. Mechanistically, total PRL1+PRL2 levels are negatively correlated with PTEN protein in the testis; loss of both PRLs elevates PTEN, attenuates Akt activation, and increases germ cell apoptosis. Knockout mice, western blot for PTEN/Akt, genetic epistasis (compound knockouts), histology Scientific reports Medium 27666520
2017 PTP4A1 promotes TGFβ signaling in dermal fibroblasts and bleomycin-induced fibrosis in vivo by enhancing ERK activity, which stimulates SMAD3 expression and nuclear translocation. Upstream of ERK, PTP4A1 directly interacts with SRC and inhibits SRC basal activation independently of its phosphatase activity. PTP4A2 minimally interacts with SRC and does not activate this pathway. Primary fibroblast overexpression/KD, Co-IP for PTP4A1–SRC interaction, in vivo bleomycin model, western blot for ERK/SMAD3, phosphatase-dead mutant Nature communications High 29057934
2007 Oxidative stress reversibly inhibits PRL-1 phosphatase activity through formation of an intramolecular disulfide bridge between Cys104 (active site) and Cys49, observed in vitro, in cultured cone cells, and in isolated retinas exposed to H2O2. In vitro phosphatase assay with H2O2 treatment, cell culture and isolated retina experiments, cycloheximide chase Biochimica et biophysica acta Medium 17673310
2019 In Drosophila, the PRL-1 ortholog is a membrane-anchored phosphatase that promotes presynapse formation on a specific axon collateral of mechanosensory neurons; loss of Prl-1 reduces CNS presynapses and causes locomotor defects. Prl-1 modulates insulin receptor (InR) signaling within a single contralateral axon compartment. Branch-specific localization and function of Prl-1 depend on untranslated regions (UTRs) of the prl-1 mRNA. Genetic loss-of-function in Drosophila, transgenic overexpression, neuron-specific imaging, InR epistasis, UTR deletion constructs Science High 31048465
2022 PTP4A1 dephosphorylates cytohesin-2 at Tyr381 in Schwann cells, reducing its activity. The adaptor SH2B1 maintains phosphorylation at Tyr381 by interacting with cytohesin-2. Schwann cell-specific knockdown of PTP4A1 increases cytohesin-2 phosphorylation and myelin thickness; loss of SH2B1 reduces phosphorylation and myelin thickness. Knockin of a non-phosphorylatable Y381F cytohesin-2 reduces Arf6 activity and myelin thickness. Knockin mice (Y381F), Schwann cell-specific conditional knockdown, Co-IP, Arf6 activity assay, sciatic nerve histology Science signaling High 35077201
2023 PRL-1/2 (PTP4A1/PTP4A2) control intracellular magnesium levels by modulating TRPM7 channel activity through CNNM transporters. CNNM inhibits TRPM7; PRL-2 overexpression counteracts ARL15-mediated CNNM3/TRPM7 complex formation, enhancing TRPM7 function and intracellular Mg²⁺. PRL-1/2 knockdown restores CNNM3–TRPM7 interaction; co-targeting TRPM7 and PRL-1/2 alters mitochondrial function and sensitizes cells to metabolic stress. Genetically encoded Mg²⁺ reporter, Co-IP for protein complex formation, TRPM7 activity assays, siRNA knockdown, mitochondrial function assays PNAS High 36972446
2023 PTP4A1 dephosphorylates the transcription factor USF1 at Ser309, increasing USF1 transcriptional activity. This induces expression of A20 (TNFAIP3), which inhibits NF-κB activity, reducing expression of cell adhesion molecules (CAMs) in endothelial cells. Ptp4a1 knockout mice show exacerbated IL-1β-induced CAM expression and atherosclerosis on a high-fat diet. shRNA knockdown and overexpression, luciferase reporter assay, ChIP assay, site-specific phosphorylation analysis, Ptp4a1 KO and transgenic mice, in vivo atherosclerosis model Cardiovascular research High 36534975
2023 PTP4A1 deficiency worsens hepatosteatosis and glucose homeostasis in high-fat diet mice. PTP4A1 activates the CREBH/FGF21 transcriptional axis to prevent lipid accumulation; liver-specific overexpression of PTP4A1 or systemic FGF21 restores metabolic phenotypes in Ptp4a1-null mice. Ptp4a1 knockout mice, AAV-mediated liver-specific overexpression, adenoviral FGF21 overexpression, hyperinsulinemic-euglycemic clamp, luciferase reporter (CREBH), immunoprecipitation, primary hepatocytes Theranostics Medium 36793871
2024 PRL-1 (and PRL-3) function as lipid phosphatases that convert PI(3,4)P2 and PI(3,5)P2 to PI(3)P on cellular membranes; this lipid phosphatase activity promotes membrane ruffles, membrane blebbing, and macropinocytosis, facilitating nutrient uptake, cell migration, and invasion. Cellular assays (membrane ruffle/bleb imaging), biochemical phosphoinositide substrate assays, protein interactome profiling, functional macropinocytosis assays Theranostics Medium 38948056
2023 PTP4A1 binds to pyruvate kinase isoenzyme M2 (PKM2) to promote its expression and to aconitase 2 (ACO2) to enhance its degradation, thereby reprogramming mitochondrial metabolism to enhance invasive capacity of oral squamous cell carcinoma cells. Co-immunoprecipitation, western blot for PKM2/ACO2, overexpression/knockdown, in vitro invasion assays, in vivo tumor model Cell death discovery Medium 37773151
2025 Crystal structure of the phosphocysteine intermediate of PRL1 (PTP4A1) determined using a C49S/D72A double mutant that stabilizes the phosphocysteine. The structure shows that phosphocysteine sterically interferes with CNNM binding. An aspartic acid (D72) mutation increases the initial rate of catalysis for PRL1/2/3, opposite to the effect seen in classical PTPs (PTP1B, PTPN12), highlighting mechanistic differences in the hydrolysis step. X-ray crystallography of phosphocysteine intermediate, mutagenesis, in vitro enzyme assays for all three PRL paralogs and classical PTPs The Journal of biological chemistry High 40398601
2025 PTP4A1 physically interacts with PTEN (confirmed by Co-IP and immunofluorescence co-localization), suppresses PTEN phosphorylation, and thereby activates the PI3K/AKT/GSK3α pathway to promote ICC cell proliferation, migration, and invasion. Co-immunoprecipitation, immunofluorescence, western blot for pathway components, overexpression and knockdown, in vivo xenograft Oncology reports Medium 40747713
2018 PRL-1 redistributes to the immunological synapse (IS) in two stages: first transiently at scanning membranes enriched in CD3 and actin, then delivered from pericentriolar CD3ζ-containing vesicles; at the established IS it distributes to LFA-1 and CD3ε sites. PRL-1 regulates actin dynamics during IS assembly and is required for IL-2 secretion; pharmacological inhibition of PRL catalytic activity reduces IL-2 secretion. Live imaging, immunofluorescence, pharmacological catalytic inhibition, siRNA knockdown, IL-2 secretion assay Frontiers in immunology Medium 30515156
1999 The transcription factor Egr-1 binds a specific site in the proximal PRL-1 promoter P1 and is sufficient to transactivate PRL-1 gene expression; an intact Egr-1 binding site is required for PRL-1 upregulation in response to mitogen stimulation. EMSA, promoter reporter assays (luciferase), mutant Egr-1 binding site, Egr-1 binding activity in regenerating liver The Journal of biological chemistry Medium 9988683
2022 PRL1 promotes glioblastoma invasion by stabilizing the EMT transcription factor Snail2 through activation of the deubiquitinase USP36; PRL1 expression activates USP36, which deubiquitinates and stabilizes Snail2, and knockdown of PRL1 blocks EMT, invasion, and tumor growth. Overexpression and knockdown, ubiquitination assays, Co-IP for PRL1-USP36-Snail2 interactions, in vivo xenograft Frontiers in oncology Medium 35111679
2024 PTP4A1 oxidized form (disulfide-bonded between Cys104 and Cys49) retains a key biological function: it forms a kinase-phosphatase complex with Src kinases independently of phosphatase activity, as demonstrated in systemic sclerosis fibroblasts. Production of oxidized and reduced PTP4A1 recombinant protein, Co-IP/complex formation assay with Src Methods in molecular biology Low 38147218

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 PRL-1, a unique nuclear protein tyrosine phosphatase, affects cell growth. Molecular and cellular biology 247 8196618
2003 PRL-3 and PRL-1 promote cell migration, invasion, and metastasis. Cancer research 234 12782572
1998 Pleiotropic control of glucose and hormone responses by PRL1, a nuclear WD protein, in Arabidopsis. Genes & development 186 9765207
2000 Prenylation-dependent association of protein-tyrosine phosphatases PRL-1, -2, and -3 with the plasma membrane and the early endosome. The Journal of biological chemistry 184 10747914
1998 Mouse PRL-2 and PRL-3, two potentially prenylated protein tyrosine phosphatases homologous to PRL-1. Biochemical and biophysical research communications 164 9514946
1999 Regulatory interaction of PRL1 WD protein with Arabidopsis SNF1-like protein kinases. Proceedings of the National Academy of Sciences of the United States of America 147 10220464
2002 The tyrosine phosphatase PRL-1 localizes to the endoplasmic reticulum and the mitotic spindle and is required for normal mitosis. The Journal of biological chemistry 108 12235145
2009 PRL1 promotes cell migration and invasion by increasing MMP2 and MMP9 expression through Src and ERK1/2 pathways. Biochemistry 97 19199380
2014 PRL1, an RNA-binding protein, positively regulates the accumulation of miRNAs and siRNAs in Arabidopsis. PLoS genetics 84 25474114
2007 PRL-1 tyrosine phosphatase regulates c-Src levels, adherence, and invasion in human lung cancer cells. Cancer research 75 17234774
2005 Structure and biochemical properties of PRL-1, a phosphatase implicated in cell growth, differentiation, and tumor invasion. Biochemistry 74 16142898
2020 Circular RNA circNRIP1 promotes migration and invasion in cervical cancer by sponging miR-629-3p and regulating the PTP4A1/ERK1/2 pathway. Cell death & disease 71 32457332
2013 MiR-339-5p regulates the growth, colony formation and metastasis of colorectal cancer cells by targeting PRL-1. PloS one 70 23696794
2007 Phosphatase activity, trimerization, and the C-terminal polybasic region are all required for PRL1-mediated cell growth and migration. The Journal of biological chemistry 70 17656357
2001 ATF-7, a novel bZIP protein, interacts with the PRL-1 protein-tyrosine phosphatase. The Journal of biological chemistry 67 11278933
2005 Trimeric structure of PRL-1 phosphatase reveals an active enzyme conformation and regulation mechanisms. Journal of molecular biology 65 15571731
2009 Pleiotropic regulatory locus 1 (PRL1) integrates the regulation of sugar responses with isoprenoid metabolism in Arabidopsis. Molecular plant 58 20008452
2016 Structural Basis of the Oncogenic Interaction of Phosphatase PRL-1 with the Magnesium Transporter CNNM2. The Journal of biological chemistry 55 27899452
2005 Generation of PRL-3- and PRL-1-specific monoclonal antibodies as potential diagnostic markers for cancer metastases. Clinical cancer research : an official journal of the American Association for Cancer Research 52 15788667
1999 Mitogenic up-regulation of the PRL-1 protein-tyrosine phosphatase gene by Egr-1. Egr-1 activation is an early event in liver regeneration. The Journal of biological chemistry 50 9988683
1996 Expression of PRL-1 nuclear PTPase is associated with proliferation in liver but with differentiation in intestine. The American journal of physiology 49 8760115
2017 PTP4A1 promotes TGFβ signaling and fibrosis in systemic sclerosis. Nature communications 48 29057934
2002 The induction of the immediate-early-genes Egr-1, PAI-1 and PRL-1 during liver regeneration in surgical models is related to increased portal flow. Journal of hepatology 47 12399226
2022 MYB43 as a novel substrate for CRL4PRL1 E3 ligases negatively regulates cadmium tolerance through transcriptional inhibition of HMAs in Arabidopsis. The New phytologist 46 35129221
2009 Modulation of O-mediated retrograde signaling by the PLEIOTROPIC RESPONSE LOCUS 1 (PRL1) protein, a central integrator of stress and energy signaling. The Plant journal : for cell and molecular biology 44 19500298
2016 Protein tyrosine phosphatase PTP4A1 promotes proliferation and epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma via the PI3K/AKT pathway. Oncotarget 42 27655691
2011 PRL-1 protein promotes ERK1/2 and RhoA protein activation through a non-canonical interaction with the Src homology 3 domain of p115 Rho GTPase-activating protein. The Journal of biological chemistry 41 22009749
2008 New p53 target, phosphatase of regenerating liver 1 (PRL-1) downregulates p53. Oncogene 40 18997816
2016 Suppression of cell migration is promoted by miR-944 through targeting of SIAH1 and PTP4A1 in breast cancer cells. BMC cancer 38 27377268
2014 PRL1 modulates root stem cell niche activity and meristem size through WOX5 and PLTs in Arabidopsis. The Plant journal : for cell and molecular biology 38 25438658
2021 Long non-coding RNA USP30-AS1 aggravates the malignant progression of cervical cancer by sequestering microRNA-299-3p and thereby overexpressing PTP4A1. Oncology letters 35 33986866
2019 Branch-restricted localization of phosphatase Prl-1 specifies axonal synaptogenesis domains. Science (New York, N.Y.) 32 31048465
1996 PRL-1, a protein tyrosine phosphatase, is expressed in neurons and oligodendrocytes in the brain and induced in the cerebral cortex following transient forebrain ischemia. Brain research. Molecular brain research 28 8840018
2017 MicroRNA-1271 functions as a metastasis and epithelial-mesenchymal transition inhibitor in human HCC by targeting the PTP4A1/c-Src axis. International journal of oncology 27 29345291
2007 Oxidative stress-induced expression and modulation of Phosphatase of Regenerating Liver-1 (PRL-1) in mammalian retina. Biochimica et biophysica acta 25 17673310
1998 The gene encoding human nuclear protein tyrosine phosphatase, PRL-1. Cloning, chromosomal localization, and identification of an intron enhancer. The Journal of biological chemistry 25 9642300
2021 Activation of the EGFR-PI3K-CaM pathway by PRL-1-overexpressing placenta-derived mesenchymal stem cells ameliorates liver cirrhosis via ER stress-dependent calcium. Stem cell research & therapy 24 34689832
1995 A 100-kb physical and transcriptional map around the EDH17B2 gene: identification of three novel genes and a pseudogene of a human homologue of the rat PRL-1 tyrosine phosphatase. Human genetics 24 8529999
2016 Role of phosphatase of regenerating liver 1 (PRL1) in spermatogenesis. Scientific reports 23 27666520
2006 Involvement of the tyrosine phosphatase early gene of liver regeneration (PRL-1) in cell cycle and in liver regeneration and fibrosis effect of halofuginone. Cell and tissue research 22 16508789
2000 PRL-1 PTPase expression is developmentally regulated with tissue-specific patterns in epithelial tissues. American journal of physiology. Gastrointestinal and liver physiology 22 10960362
2012 Tissue-specific alterations of PRL-1 and PRL-2 expression in cancer. American journal of translational research 20 22347524
2023 PRL-1/2 phosphatases control TRPM7 magnesium-dependent function to regulate cellular bioenergetics. Proceedings of the National Academy of Sciences of the United States of America 19 36972446
2021 LncRNA NEAT1 promotes cell proliferation, migration, and invasion via the miR-186-5p/PTP4A1 axis in cholangiocarcinoma. The Kaohsiung journal of medical sciences 18 33502823
2018 miR-339-5p Increases Radiosensitivity of Lung Cancer Cells by Targeting Phosphatases of Regenerating Liver-1 (PRL-1). Medical science monitor : international medical journal of experimental and clinical research 18 30462625
2023 Endothelial PTP4A1 mitigates vascular inflammation via USF1/A20 axis-mediated NF-κB inactivation. Cardiovascular research 17 36534975
1999 Developmental expression of the murine Prl-1 protein tyrosine phosphatase gene. The Journal of experimental zoology 16 10194868
2020 Enhanced PRL-1 expression in placenta-derived mesenchymal stem cells accelerates hepatic function via mitochondrial dynamics in a cirrhotic rat model. Stem cell research & therapy 15 33246509
2013 Drosophila PRL-1 is a growth inhibitor that counteracts the function of the Src oncogene. PloS one 14 23577193
2021 PRL-1 overexpressed placenta-derived mesenchymal stem cells suppress adipogenesis in Graves' ophthalmopathy through SREBP2/HMGCR pathway. Stem cell research & therapy 13 34051850
2014 Identification of PRL1 as a novel diagnostic and therapeutic target for castration-resistant prostate cancer by the Escherichia coli ampicillin secretion trap (CAST) method. Urologic oncology 13 24968948
2012 Increased expression of PRL-1 protein correlates with shortened patient survival in human hepatocellular carcinoma. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 13 22484636
2022 PRL1 Promotes Glioblastoma Invasion and Tumorigenesis via Activating USP36-Mediated Snail2 Deubiquitination. Frontiers in oncology 10 35111679
2022 GINS2 regulates the proliferation and apoptosis of colon cancer cells through PTP4A1. Molecular medicine reports 10 35137928
2023 Hepatic PTP4A1 ameliorates high-fat diet-induced hepatosteatosis and hyperglycemia by the activation of the CREBH/FGF21 axis. Theranostics 9 36793871
2023 Protein kinase ATR inhibits E3 ubiquitin ligase CRL4PRL1 to stabilize ribonucleotide reductase in response to replication stress. Cell reports 9 37354461
2023 PTP4A1 promotes oral squamous cell carcinoma (OSCC) metastasis through altered mitochondrial metabolic reprogramming. Cell death discovery 9 37773151
2005 Exclusion of four candidate genes, KHDRBS2, PTP4A1, KIAA1411 and OGFRL1, as causative of autosomal recessive retinitis pigmentosa. Ophthalmic research 9 16192744
2024 The C2H2 family protein ZAT17 engages in the cadmium stress response by interacting with PRL1 in Arabidopsis. Journal of hazardous materials 8 38237437
2024 WTAP promotes proliferation of esophageal squamous cell carcinoma via m6A-dependent epigenetic promoting of PTP4A1. Cancer science 8 38746998
2022 The adaptor SH2B1 and the phosphatase PTP4A1 regulate the phosphorylation of cytohesin-2 in myelinating Schwann cells in mice. Science signaling 8 35077201
2012 Pleiotropic regulatory locus 2 exhibits unequal genetic redundancy with its homolog PRL1. Plant & cell physiology 8 22813545
2024 PRL1 and PRL3 promote macropinocytosis via its lipid phosphatase activity. Theranostics 7 38948056
2022 Inhibitory Effect of miR-339-5p on Glioma through PTP4A1/HMGB1 Pathway. Disease markers 6 35872698
2018 Phosphatase of Regenerating Liver-1 (PRL-1) Regulates Actin Dynamics During Immunological Synapse Assembly and T Cell Effector Function. Frontiers in immunology 6 30515156
1996 Localization of the human phosphotyrosine phosphatase-related genes (h-PRL-1) to chromosome bands 1p35-p34, 17q12-q21, 11q24-q25 and 12q24. Human genetics 6 8931711
2022 Long noncoding RNA DLEU2 promotes growth and invasion of hepatocellular carcinoma by regulating miR-30a-5p/PTP4A1 axis. Pathology, research and practice 5 36049439
2022 Circular RNA circ_0000212 accelerates cervical cancer progression by acting as a miR-625-5p sponge to upregulate PTP4A1. Anti-cancer drugs 4 36729102
2023 Increased PRL-1 in BM-derived MSCs triggers anaerobic metabolism via mitochondria in a cholestatic rat model. Molecular therapy. Nucleic acids 3 36865088
2009 1H, 15N, 13C resonance assignments of the reduced and active form of human Protein Tyrosine Phosphatase, PRL-1. Biomolecular NMR assignments 3 19636948
2024 PRL1 interacts with and stabilizes RPA2A to regulate carbon deprivation-induced senescence in Arabidopsis. The New phytologist 2 39229867
2023 Expression of PTP4A1 in circulating tumor cells and its efficacy evaluation in patients with early- and intermediate-stage esophageal cancer. Medicine 2 38134119
2025 The ZAT17-PRL1 module engages in the miRNA synthesis in Arabidopsis. Plant physiology and biochemistry : PPB 1 40479889
2022 Phosphatase of Regenerating Liver-1 (PRL-1)-Overexpressing Placenta-Derived Mesenchymal Stem Cells Enhance Antioxidant Effects via Peroxiredoxin 3 in TAA-Injured Rat Livers. Antioxidants (Basel, Switzerland) 1 36670907
2025 Structure of the phosphocysteine intermediate of the phosphatase of regenerating liver PTP4A1. The Journal of biological chemistry 0 40398601
2025 PTP4A1 promotes intrahepatic cholangiocarcinoma development and progression by interacting with PTEN and activating the PI3K/AKT/GSKα axis. Oncology reports 0 40747713
2025 GINS2 promotes oral squamous cell carcinoma progression and immune evasion by recruiting PD-L1+ neutrophils and modulating the PTP4A1/PKM2 axis. Frontiers in immunology 0 41322418
2025 Protein Tyrosine Phosphatase 4A1 (PTP4A1) Regulates Early Events in Colorectal Cancer Intraperitoneal Dissemination in the Aged Male Host. Aging and cancer 0 41769321
2024 Preparation of Oxidized and Reduced PTP4A1 for Structural and Functional Studies. Methods in molecular biology (Clifton, N.J.) 0 38147218