Affinage

PTPRF

Receptor-type tyrosine-protein phosphatase F · UniProt P10586

Length
1907 aa
Mass
212.9 kDa
Annotated
2026-06-10
100 papers in source corpus 53 papers cited in narrative 53 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

PTPRF (LAR) is a transmembrane receptor protein tyrosine phosphatase that couples cell-surface adhesion to intracellular tyrosine dephosphorylation, governing growth-factor signaling, cell adhesion/apoptosis, and synapse organization (PMID:1695146, PMID:7852302, PMID:15750591). Its tandem cytoplasmic domains are functionally divided: the membrane-proximal D1 domain is the catalytic unit, acting through a covalent phosphoenzyme intermediate that depends on an essential active-site cysteine (C1522), whose oxidation by peroxynitrile irreversibly inactivates the enzyme, while the membrane-distal D2 domain lacks catalytic activity but regulates D1 activity and mediates substrate and partner association (PMID:1918076, PMID:1370625, PMID:10486138, PMID:11158333). LAR is expressed as a non-covalently associated two-subunit complex generated by subtilisin-like proprotein cleavage, and its phosphatase function is downregulated by regulated ectodomain shedding and sequential proteolysis—via PKC, EGFR/ERK-driven ADAM-17/TACE cleavage, and presenilin/γ-secretase processing that liberates a LAR intracellular domain (LICD) repressing β-catenin target transcription (PMID:1547787, PMID:8089133, PMID:9245795, PMID:16478662, PMID:17259169). As a phosphatase, LAR negatively regulates multiple receptor tyrosine kinases, dephosphorylating and physically associating with the insulin receptor to restrain PI3-kinase and downstream signaling (with in vivo roles in glucose homeostasis and insulin action) and acting on EGFR, c-Met (contact inhibition of HGF signaling), and IRS proteins (PMID:7852302, PMID:8732688, PMID:8995282, PMID:9519761, PMID:11309481, PMID:16415345); it also dephosphorylates EphA2-pY930 to uncouple Nck1 and attenuate migration, dephosphorylates and destabilizes p130Cas to induce apoptosis, and activates DAPK by removing inhibitory pY491/492 (PMID:10320483, PMID:17803936, PMID:23358419). LAR organizes signaling at focal adhesions through liprin-α/LIP.1 and the Trio GEF, and crystallographic and cellular work shows liprin-α promotes LAR clustering via a homophilic D1–D1 interaction that negatively regulates phosphatase activity (PMID:7796809, PMID:8643598, PMID:9624153, PMID:31924785). At synapses, presynaptic LAR functions as a trans-synaptic adhesion hub whose Ig/FNIII ectodomains engage postsynaptic partners NGL-3, Slitrks, SALM3, and heparan-sulfate-modified neurexins in a splicing-dependent manner to drive bidirectional synaptic differentiation and NMDA receptor-mediated transmission, signaling intracellularly through liprin-α and the adaptor Caskin to control synapse and active-zone organization and axon guidance (PMID:15750591, PMID:19252495, PMID:20139422, PMID:26321637, PMID:31985401, PMID:33037075, PMID:21430143). LAR is additionally a receptor for chondroitin sulfate proteoglycans that signals through Rho/ROCK to restrict neural precursor neurogenesis and modulate neuroinflammation (PMID:25703008, PMID:29558941).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1991 High

    Established the catalytic logic of LAR's two cytoplasmic domains—answering whether both phosphatase-like domains are active and how catalysis proceeds.

    Evidence Bacterial expression, site-directed mutagenesis, and phosphoenzyme intermediate trapping defining C1522 as the catalytic cysteine and D1 as the sole active domain

    PMID:1370625 PMID:1695146 PMID:1918076

    Open questions at the time
    • Physiological substrates not yet identified in this period
    • Regulatory role of D2 only inferred, not mechanistically resolved
  2. 1992 Medium

    Defined D2 as a non-catalytic regulatory domain modulating D1 activity, refining the division of labor between the tandem domains.

    Evidence Purified recombinant D1 vs. D1D2 fragments with polycation stimulation and substrate-specificity comparison

    PMID:1318316 PMID:1370625 PMID:1645351

    Open questions at the time
    • Endogenous regulators substituting for polycations not identified
    • Structural basis of D2 modulation unresolved at this stage
  3. 1994 High

    Established that LAR is a proteolytically processed two-subunit receptor whose ectodomain shedding regulates its function, linking processing to phosphatase regulation.

    Evidence Scanning and site-directed mutagenesis mapping proprotein cleavage, subunit association, and shedding sites in transfected cells

    PMID:1547787 PMID:8089133

    Open questions at the time
    • The shedding protease and physiological triggers not identified here
    • Fate of the cytoplasmic fragment after shedding unknown
  4. 1997 High

    Identified the insulin receptor as a direct physical and functional LAR substrate and placed LAR control at growth-factor signaling, defining its role as a negative RTK regulator in cells and in vivo.

    Evidence Antisense knockdown, overexpression with domain-specific controls, reciprocal co-IP, endosomal fractionation, and kinetic dephosphorylation assays across insulin/EGF/HGF receptors

    PMID:7852302 PMID:8557682 PMID:8732688 PMID:8995282 PMID:9207225

    Open questions at the time
    • Site-specific dephosphorylation residues on the receptors not mapped
    • Whether association is constitutive or signaling-dependent only partially resolved
  5. 1998 High

    Identified liprin-α/LIP.1 and Trio as D2-binding partners that localize and assemble LAR into adhesion and clustering complexes, establishing the scaffolding arm of LAR signaling.

    Evidence Interaction-trap/yeast two-hybrid identification, co-localization at focal adhesions, GEF activity assays, and co-expression-induced LAR clustering

    PMID:7796809 PMID:8643598 PMID:9624153

    Open questions at the time
    • Functional consequence of clustering on catalytic activity not yet resolved in this period
    • Whether Trio is a substrate or pure complex partner left open
  6. 1998 High

    Defined in vivo developmental and metabolic roles via mouse knockouts—mammary alveolar differentiation, glucose homeostasis, and cholinergic neuron networks—establishing LAR as physiologically required across tissues.

    Evidence Gene-trap and gene-targeted knockout mice with histological, neuroanatomical, and euglycemic-clamp metabolic phenotyping

    PMID:9039657 PMID:9245518 PMID:9519761

    Open questions at the time
    • Cell-autonomous vs. systemic contributions not fully separated
    • Specific substrates underlying each tissue phenotype not identified in these studies
  7. 1999 High

    Established p130Cas as an in vivo substrate whose LAR-mediated dephosphorylation and destabilization drives apoptosis, linking LAR catalysis to cell-death control.

    Evidence Overexpression with phosphatase-dead mutants, in vitro dephosphorylation, co-localization, and p130Cas rescue of LAR-induced apoptosis

    PMID:10320483 PMID:9501065

    Open questions at the time
    • Mechanism linking p130Cas destabilization to caspase activation not detailed
    • Context determining apoptotic vs. signaling outcomes unresolved
  8. 1999 High

    Showed the catalytic cysteine is a redox target irreversibly inactivated by peroxynitrite, identifying a chemical mode of LAR regulation.

    Evidence In vitro kinetic phosphatase assays with peroxynitrite, NO donors, GSNO, and DTT reversal tests

    PMID:10486138

    Open questions at the time
    • Physiological relevance of peroxynitrite inactivation in cells not established
    • No demonstration of reversible redox cycling in vivo
  9. 2006 High

    Resolved the proteases and kinase pathways driving regulated LAR processing and intracellular-domain generation, connecting RTK activity to LAR downregulation and β-catenin-dependent transcription.

    Evidence TACE-knockout fibroblasts, dominant-negative TACE, γ-secretase and α-secretase inhibitors, presenilin-deficient cells, co-IP, and a cyclin D1 reporter

    PMID:16478662 PMID:17259169 PMID:9245795

    Open questions at the time
    • Quantitative contribution of LICD to nuclear signaling in vivo unknown
    • Whether shed ectodomain has independent signaling activity not addressed
  10. 2007 High

    Expanded the LAR substrate/effector network to neurotrophic and migration control—activating Src to transactivate TrkB and reciprocally regulating DAPK with Src—establishing context-dependent pro- and anti-migratory roles.

    Evidence LAR-knockout/siRNA neurons, reciprocal co-IP, Src inhibitor PP2, in vitro DAPK dephosphorylation with site mutagenesis, and migration/apoptosis readouts

    PMID:17013927 PMID:17803936

    Open questions at the time
    • Direct LAR target site on Src (regulatory tyrosine) inferred but not crystallographically mapped
    • Switch determining LAR vs. Src dominance over DAPK not fully defined
  11. 2009 High

    Identified LAR as a presynaptic trans-synaptic adhesion receptor engaging postsynaptic NGL-3 to induce bidirectional synaptic differentiation, opening LAR's synaptic organizer function.

    Evidence Co-culture synaptogenesis assays, heterologous expression, NGL-3 RNAi, soluble-LAR competition, and electrophysiology

    PMID:15750591 PMID:19252495

    Open questions at the time
    • How synaptic adhesion couples to or operates independently of phosphatase activity not resolved
    • Endogenous splicing isoform requirements not yet mapped here
  12. 2015 High

    Defined a splicing-dependent code for LAR's postsynaptic partner selection (Slitrks, SALM3, HS-neurexins) and mapped the extracellular domains and residues mediating these interactions structurally.

    Evidence Domain/point mutagenesis, crystal structures of Ig/FNIII–ligand complexes, splice-insert requirement analysis, knockout mice, and co-culture synaptogenesis

    PMID:20139422 PMID:23345436 PMID:25394468 PMID:26321637 PMID:33037075

    Open questions at the time
    • In vivo necessity of individual partners separable from redundancy across LAR-RPTPs not fully dissected
    • Higher-order assembly seen in crystals not directly visualized at native synapses
  13. 2016 High

    Linked LAR catalytic activity to adhesion and cell-cycle signaling through a c-Abl/Akt/CDK1 axis, and identified EphA2-pY930 as a site-specific substrate uncoupling Nck1 to limit migration.

    Evidence Phosphatase-deficient knock-in MEFs with phosphoproteomics and kinase inhibition; siRNA RPTP screen with site-specific EphA2 dephosphorylation and migration assays

    PMID:23358419 PMID:23418360 PMID:27352860 PMID:31799666

    Open questions at the time
    • Direct vs. indirect dephosphorylation steps in the CDK1 axis not fully separated
    • Transcriptional regulation of PTPRF (miR-24, PPARγ) integration with phosphatase output incompletely mapped
  14. 2020 High

    Resolved the structural and functional basis of LAR clustering—a homophilic D1–D1 interaction stabilized by liprin-α oligomerization that negatively regulates phosphatase activity—unifying scaffolding and catalytic control.

    Evidence Crystal structure of LAR D1D2–liprin-α3 SAM complex, D1/D1 interface mutagenesis, cellular clustering, and dephosphorylation assays

    PMID:31924785

    Open questions at the time
    • Whether activity-suppressing clustering operates at synapses vs. adhesions not directly compared
    • Triggers shifting LAR between clustered (low-activity) and dispersed states unknown
  15. 2020 High

    Dissociated LAR-RPTP synaptic adhesion from synapse number in vivo—triple knockouts preserve synapse count but selectively impair NMDA receptor-mediated transmission—refining the synaptic role to functional modulation.

    Evidence Conditional triple-knockout mice with electrophysiology, superresolution synaptic-cleft localization, and EM of active-zone architecture

    PMID:16476662 PMID:21430143 PMID:31985401 PMID:33656439

    Open questions at the time
    • Mechanism linking trans-synaptic LAR to NMDA receptor function unresolved
    • Redundancy among LAR-RPTP family members complicates attributing roles to PTPRF specifically

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LAR integrates its dual identity—catalytic phosphatase versus phosphatase-independent adhesion organizer—and what switches it between activity states across adhesion, growth-factor, and synaptic contexts remains unresolved.
  • No unified model of when adhesion engagement modulates catalytic output
  • In vivo substrate repertoire of PTPRF in distinct tissues incompletely defined
  • Functional separation of PTPRF from paralogs PTPσ/PTPδ in shared phenotypes still limited

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0060090 molecular adaptor activity 3 GO:0098631 cell adhesion mediator activity 3 GO:0016787 hydrolase activity 2 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 2 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-1266738 Developmental Biology 3 R-HSA-5357801 Programmed Cell Death 2
Partners
CASKIN1INSRMETNGL-3 (LRRC4B)NRXN1PPFIA1/LIPRIN-Α (LIP.1)SLITRKTRIO
Complex memberships
LAR E-subunit/P-subunit receptor complexLAR–liprin-α cluster

Evidence

Reading pass · 53 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 The first of the two intracellular PTPase-like domains of LAR has catalytic enzyme activity, while the second domain lacks detectable catalytic activity. A single conserved cysteine residue in domain 1 is absolutely required for activity; substitution at this position abolished activity. Sequences in domain 2 influence substrate specificity. Deletion and point mutations in cytoplasmic region; in vitro phosphatase activity assays with multiple substrates The EMBO journal High 1695146
1991 The cytoplasmic domain of rat LAR expressed in bacteria has protein tyrosine phosphatase activity. Cys-1522 in domain 1 is the catalytic cysteine; C1522S mutation causes >99% loss of activity. A covalent phosphoenzyme intermediate was trapped with 32P-labeled substrate, establishing the catalytic mechanism. The inactive C1522S mutant could be phosphorylated in vitro by PKC and v-abl tyrosine kinase. Bacterial expression, purification, site-directed mutagenesis, phosphoenzyme intermediate trapping by SDS-PAGE autoradiography, in vitro kinase assays The Journal of biological chemistry High 1918076
1991 Temperature-sensitive and thermostable missense mutations in LAR domain 1 cluster between amino acid positions 1329–1407, identifying a structurally critical region for enzyme folding and activity. A second-site revertant (C1446-Y) suppresses multiple temperature-sensitive mutations, suggesting structural interactions within this region. Bacterial expression of LAR domain 1; hydroxylamine and MNNG mutagenesis; biochemical characterization of mutants at permissive and restrictive temperatures; second-site reversion analysis The Journal of biological chemistry Medium 1645351
1992 LAR is expressed on the cell surface as a complex of two non-covalently associated subunits (E-subunit ~150 kDa extracellular; P-subunit ~85 kDa transmembrane+cytoplasmic) derived from a proprotein. Proprotein cleavage occurs intracellularly at a paired basic amino acid site by a subtilisin-like endoprotease; mutation of key arginine residues blocks cleavage. The E-subunit is shed from the cell surface during cell growth, providing a mechanism to regulate LAR phosphatase function. Mutational analysis of cleavage site; biochemical characterization of subunit expression; cell surface shedding assays The EMBO journal High 1547787
1992 The E. coli-expressed LAR two-domain fragment (D1D2) has almost identical specific activity to the single domain (D1) fragment, confirming a single functional active site in domain 1. 18O exchange from [18O4]-inorganic phosphate into water and 32P-phosphoenzyme labeling established a phosphoenzyme intermediate mechanism. Polycationic polypeptides stimulate D1D2 but not D1 PTPase activity via domain 2, indicating domain 2 has a regulatory function. E. coli expression and purification; isotope exchange assay (18O); phosphoenzyme intermediate labeling; substrate specificity comparison; polycation stimulation assay Biochemistry High 1370625
1992 Basic polypeptides stimulate the PTPase activity of LAR D1D2 but not D1 alone using peptide substrate Raytide, indicating that domain 2 has a regulatory function on domain 1 catalytic activity. Polypeptides containing high proportions of tyrosine are inhibitory to LAR and related phosphatases. Purified recombinant LAR fragments from E. coli; peptide substrate assays with modulatory compounds The Journal of biological chemistry Medium 1318316
1994 Functional regions for LAR proprotein processing, subunit association, and shedding were mapped by scanning mutagenesis. Three residues (two in a penta-arginine sequence and one C-terminal to the cleavage site) are essential for proprotein cleavage. Several non-contiguous residues in the P-subunit ectodomain are required for subunit association. Shedding involves a second proteolytic cleavage within the P-subunit ectodomain near the transmembrane peptide. Site-directed and scanning mutagenesis; biochemical analysis of processing, subunit association, and shedding in transfected cells The Journal of biological chemistry High 8089133
1995 LAR co-localizes with the novel cytoplasmic 160 kDa phosphoserine protein LIP.1 (LAR-interacting protein 1) at the ends of focal adhesions most proximal to the cell nucleus. LIP.1 binds specifically to the membrane-distal D2 PTPase domain of LAR and appears to localize LAR to focal adhesions, implicating this complex in regulation of focal adhesion disassembly. Identification of LIP.1 by interaction-trap assay; co-localization by immunofluorescence; domain-binding analysis The EMBO journal High 7796809
1995 Antisense-mediated suppression of LAR in McA-RH7777 hepatoma cells (63% reduction) increased insulin-dependent insulin receptor autophosphorylation (~150%), receptor tyrosine kinase activity (35%), and insulin-dependent PI3-kinase activity (350%), establishing LAR as a negative regulator of insulin receptor signaling in intact cells. Antisense RNA expression in hepatoma cells; insulin receptor autophosphorylation and kinase assays; PI3-kinase activity assay The Journal of biological chemistry High 7852302
1995 LAR, PTPδ, and PTPσ all interact with LIP.1 via their membrane-distal phosphatase domains. All three phosphatases exhibit similar in vitro PTPase activities and share alternative splicing of mini-exons, establishing them as a subfamily with conserved structure, activity, and interacting proteins. Cloning; in vitro PTPase activity assays; LIP.1 binding/interaction analysis across family members Proceedings of the National Academy of Sciences of the United States of America Medium 8524829
1995 Overexpression of full-length LAR in McA-RH7777 hepatoma cells (2.4-fold increase) reduced insulin receptor autophosphorylation 40% in intact cells, decreased IRS-1 and Shc tyrosine phosphorylation, and reduced IRS-1-associated PI3-kinase activity to 47% of control. Overexpression of the cytoplasmic domain alone (cytosolic, not membrane-localized) had no significant effect, indicating transmembrane localization is required for LAR to act on the insulin receptor. Stable transfection with full-length vs. cytoplasmic-only LAR constructs; insulin receptor autophosphorylation; substrate phosphorylation; kinase assays; cell fractionation Molecular endocrinology High 8732688
1996 Trio, a 2861-amino acid multidomain protein, was identified as a LAR-interacting protein via the interaction-trap assay. Trio contains two GEF domains (one Rac-specific, one Rho-specific) and a serine/threonine kinase domain. Trio appears phosphorylated only on serine residues, suggesting it is not a LAR substrate but forms a signaling complex with LAR at focal adhesions. Interaction-trap (yeast two-hybrid) assay; GEF activity assays for Rac and Rho specificity; phosphorylation analysis; co-localization at focal adhesions Proceedings of the National Academy of Sciences of the United States of America High 8643598
1996 Antisense suppression of LAR in McA-RH7777 cells increased EGF receptor autophosphorylation by >300%, HGF receptor autophosphorylation by >250%, downstream IRS-1 and Shc phosphorylation, MAP kinase activation, and PI3-kinase activation in response to all three growth factors, demonstrating LAR modulates signaling by multiple receptor tyrosine kinases. Antisense RNA suppression; receptor autophosphorylation assays; substrate phosphorylation; MAP kinase and PI3-kinase activity assays for EGF, HGF, and insulin receptors The Journal of biological chemistry High 8557682
1997 LAR co-immunoprecipitates with the insulin receptor in intact CHO cells overexpressing both proteins; up to 11.8% of LAR co-precipitates with the insulin receptor. The association was increased by cross-linking and 3.9-fold by insulin treatment. In insulin-stimulated rat liver, LAR was enriched in endosomes with the insulin receptor, and LAR-neutralizing antibodies decreased endosomal insulin receptor dephosphorylation by 28%, demonstrating a direct physical and functional association. Co-immunoprecipitation; chemical cross-linking; subcellular fractionation of rat liver; in situ endosomal dephosphorylation with neutralizing antibodies The Journal of biological chemistry High 8995282
1997 LAR and PTPσ undergo induced proteolytic processing (shedding of extracellular domains) upon treatment with calcium ionophore A23187 or phorbol ester TPA; TPA-induced LAR processing required PKCα overexpression in 293 cells. Both phosphatases localize preferentially to adherens junctions and desmosomes, co-localizing with plakoglobin. Direct association of plakoglobin and β-catenin with the intracellular domain of LAR was demonstrated in vitro. After ectodomain shedding, catalytically active intracellular portions are internalized away from cell-cell contacts. Inducible proteolytic processing; confocal microscopy; in vitro binding assay for β-catenin and plakoglobin; PKCα overexpression; inhibitor studies; cell fractionation The Journal of cell biology High 9245795
1997 LAR antisense suppression in McA-RH7777 cells prolonged insulin receptor dephosphorylation 2.6-fold (t½ increased from 34 to 87 s), providing direct kinetic evidence that LAR is a major physiological regulator of insulin receptor dephosphorylation in situ. EGF receptor dephosphorylation was also prolonged in LAR-deficient cells. Antisense RNA suppression; kinetic dephosphorylation assay following acid elution of surface-bound insulin; EGF receptor dephosphorylation assay Biochemical and biophysical research communications High 9207225
1997 LAR deficiency in transgenic mice (gene trap) results in reduced size of basal forebrain cholinergic neurons and markedly decreased cholinergic innervation of the dentate gyrus, establishing LAR as required for formation and/or maintenance of cholinergic neuronal networks in mammals. Gene trap transgenic mice with reduced LAR expression; histomorphometry of basal forebrain cholinergic neurons; immunohistochemistry of hippocampal cholinergic innervation Journal of neuroscience research Medium 9039657
1997 Knockout mice lacking both LAR phosphatase domains (LAR−/−) develop impaired terminal differentiation of mammary gland alveoli during late pregnancy, failing to switch to a lactational state and showing rapid postpartum involution. LAR expression peaks around day 16 of gestation in wild-type mice, establishing LAR-mediated signaling as required for mammary gland development and lactation. Gene targeting in mouse ES cells; histological analysis of mammary gland; Northern blot for LAR expression during pregnancy; neonatal survival assessment Developmental biology High 9245518
1998 Overexpression of wild-type LAR (but not a truncated extracellular-only form) in mammalian cells activates the caspase pathway and induces p53-independent apoptosis, establishing a role for LAR's phosphatase-active intracellular region in cell-death control. Inducible expression system; caspase activity assays; cell viability assays comparing full-length vs. extracellular-only truncation mutant Current biology Medium 9501065
1998 Alpha-liprins (a family of seven LAR-interacting proteins) bind to the membrane-distal phosphatase domains of LAR family members via their C-terminal non-coiled coil regions; beta-liprins interact with alpha-liprins. Co-expression of liprin-α2 alters LAR cellular localization and induces LAR clustering, establishing liprins as regulators of LAR localization at specific plasma membrane sites. Yeast two-hybrid and biochemical binding assays; co-expression localization studies by immunofluorescence; family-wide interaction mapping The Journal of biological chemistry High 9624153
1998 LAR-deficient mice exhibit significantly lower fasting plasma insulin and glucose and a reduced rate of hepatic glucose production, but display paradoxical resistance to insulin-stimulated glucose disposal and a 47% reduction in insulin-stimulated PI3-kinase activity in liver, demonstrating LAR has a physiological role in insulin action and glucose homeostasis in vivo. Insertional mutagenesis knockout mice; euglycemic clamp studies; hepatic PI3-kinase activity; glucose disposal measurements Diabetes High 9519761
1999 LAR overexpression specifically decreases the steady-state level and tyrosine phosphorylation of p130Cas by dephosphorylating it, reducing its protein stability. This is blocked by tyrosine phosphatase inhibitors and phosphatase-domain deletion mutants of LAR. LAR preferentially dephosphorylates p130Cas in vitro. LAR and p130Cas co-localize along stress fibers and at focal adhesions. Restoring p130Cas levels alleviates LAR-induced apoptosis, establishing p130Cas as an in vivo substrate of LAR mediating apoptosis. Overexpression of LAR and phosphatase-dead mutants; in vitro phosphatase assay; immunofluorescence co-localization; p130Cas rescue experiment; pharmacological inhibition Genes to cells High 10320483
1999 LAR is irreversibly inactivated by peroxynitrite (IC50 ≤0.9 µM) with a bimolecular rate constant of 2.3 × 10^7 M^−1 s^−1, among the fastest reactions of peroxynitrite with biological molecules. The inactivation was essentially irreversible (DTT restores <10% activity), consistent with oxidation of the essential active-site thiolate. Nitric oxide and S-nitrosoglutathione caused only partial, reversible inhibition. In vitro phosphatase activity assays; competition kinetics with cysteine; treatment with peroxynitrite, NO donors, and GSNO; DTT reversal experiments Archives of biochemistry and biophysics High 10486138
2000 Stable antisense-mediated knockdown of LAR in PC12 cells results in a two-fold increase specifically in NGF-induced (but not FGF-induced) neurite outgrowth and a two- to three-fold decrease in serum-deprivation-induced cell death, demonstrating that endogenous LAR negatively regulates neurotrophin responses and promotes cell death. Stable antisense transfection; neurite outgrowth quantification; serum deprivation cell death assay; comparison of NGF vs. FGF responses Journal of neurobiology Medium 10699984
2001 Overexpression of LAR specifically in muscle of transgenic mice causes whole-body insulin resistance: fasting insulin elevated 2.5-fold, glucose disposal reduced 39–50%, IRS-2 phosphorylation reduced 62%, and PI3-kinase associated with phosphotyrosine, IRS-1, and IRS-2 reduced 34–57%. Normal insulin receptor and IRS-1 phosphorylation was observed, suggesting dephosphorylation of specific IRS protein regulatory phosphotyrosines as the mechanism. Muscle-specific transgenic mice overexpressing human LAR; euglycemic clamp; insulin receptor and IRS phosphorylation; PI3-kinase activity assays Proceedings of the National Academy of Sciences of the United States of America High 11309481
2001 Domain 2 of LAR mediates substrate (insulin receptor) association (C1813S mutation weakened association), while domain 1 catalytic activity (C1522S mutation) is required for dephosphorylation. The extracellular domains of both LAR and insulin receptor also contribute to their association. LAR is phosphorylated by insulin receptor tyrosine kinase and autodephosphorylates via domain 1. Cysteine-to-serine active-site mutants of each domain; co-immunoprecipitation with insulin receptor; phosphorylation assays; domain deletion analysis Molecular endocrinology High 11158333
2005 LAR-RPTP is concentrated at mature excitatory synapses in hippocampal neurons. RNAi knockdown of LAR or dominant-negative disruption causes loss of excitatory synapses and dendritic spines, reduction of surface AMPA receptors, impaired dendritic targeting of the cadherin–β-catenin complex, and reduced mEPSC amplitude and frequency. β-catenin and GluR2/3 co-immunoprecipitate with liprin-α and GRIP from rat brain, establishing LAR as required for excitatory synapse development and AMPA receptor trafficking. RNAi knockdown; dominant-negative expression; immunofluorescence; electrophysiology (mEPSC recording); co-immunoprecipitation from brain extracts; surface receptor biotinylation Nature neuroscience High 15750591
2006 Drosophila HSPGs Syndecan (Sdc) and Dallylike (Dlp) both bind at high affinity to the receptor tyrosine phosphatase LAR. Double mutant analysis showed LAR is required for actions of both HSPGs at the NMJ: Sdc promotes LAR-dependent presynaptic terminal growth, while Dlp inhibits LAR activity. These results establish HSPGs as extracellular ligands that differentially regulate LAR. High-affinity binding assays; Drosophila genetics with single and double mutants; NMJ morphological analysis; epistasis analysis Neuron High 16476662
2006 LAR associates with c-Met/HGF receptor specifically in confluent (contact-inhibited) hepatocytes. LAR activity and expression increase after HGF stimulation in confluent but not sparse cells. Purified LAR dephosphorylates tyrosine-phosphorylated c-Met in vitro. Antisense knockdown of LAR in confluent cells restores prolonged c-Met phosphorylation and mitogenic response, establishing LAR as mediating contact-inhibition of HGF/c-Met signaling via dephosphorylation. Co-immunoprecipitation; in vitro LAR phosphatase assay with c-Met substrate; antisense oligonucleotides; cell density-dependent signaling assays; kinase activity measurements The Journal of biological chemistry High 16415345
2006 EGFR associates with LAR and induces proteolytic processing (cleavage) of the LAR P-subunit via an ERK1/2-dependent pathway. EGFR-induced LAR shedding is mediated by the metalloproteinase ADAM-17/TACE (established by TACE-knockout fibroblasts and dominant-negative TACE). Cleavage results in degradation of the catalytic LAR P-subunit and significantly reduced cellular phosphatase activity. EGFR overexpression and stimulation; TACE-knockout fibroblasts; dominant-negative TACE; metalloproteinase inhibitor (Batimastat); PKC inhibitors; ERK inhibitors; immunoblotting for LAR cleavage products; phosphatase activity assay Cellular signalling High 16478662
2006 LAR co-immunoprecipitates with TrkB and this interaction is increased by BDNF. In LAR-deficient neurons, BDNF-induced activation of TrkB, Shc, AKT, ERK, and CREB was significantly decreased. LAR promotes neurotrophic signaling via Src: LAR-deficient neurons show increased Src regulatory domain phosphorylation (indicating Src inactivation), Src co-immunoprecipitates with LAR, and Src inhibitor PP2 blocks LAR's ability to augment TrkB signaling. Co-immunoprecipitation; LAR knockout neurons; LAR siRNA; LAR transfection; BDNF-stimulated signaling assays; Src inhibitor PP2; immunostaining Journal of neurobiology High 17013927
2007 LAR dephosphorylates DAPK at pY491/492 to stimulate DAPK catalytic, pro-apoptotic, and anti-adhesion/anti-migration activities. Conversely, Src phosphorylates DAPK at Y491/492 to inactivate it. Upon EGF stimulation, Src activation followed by LAR downregulation synergistically inactivate DAPK, facilitating tumor cell migration. These results establish DAPK as a substrate of LAR and identify reciprocal regulation by LAR and Src. In vitro dephosphorylation assays; site-directed mutagenesis of DAPK Y491/492; kinase activity assays; DAPK apoptosis and migration readouts; EGF stimulation experiments; LAR knockdown Molecular cell High 17803936
2007 CaMKII-mediated degradation of liprin-α1 (via the ubiquitin-proteasome system activated by synaptic activity) reduces liprin-α1 protein levels and impairs dendritic targeting of LAR. Liprin-α1 mutants immune to CaMKII degradation impair dendrite arborization, reduce spine and synapse numbers, and inhibit LAR dendritic targeting, establishing that regulated liprin-α1 degradation controls LAR distribution and downstream dendrite development. CaMKII overexpression; proteasome inhibitors; liprin-α1 CaMKII-resistant mutants; hippocampal neuron imaging; dendrite, spine, synapse quantification Developmental cell High 17419996
2007 LAR is sequentially cleaved by alpha-secretase and then presenilin/gamma-secretase to generate a LAR intracellular domain (LICD). Inhibition of gamma-secretase increases LAR C-terminal fragments; prior ectodomain shedding by alpha-secretase is required (TAPI-1 blocks C-terminal fragment accumulation). Endogenous tyrosine-phosphorylated β-catenin co-immunoprecipitates with LAR; when gamma-secretase is inhibited, LAR–β-catenin association diminishes. LICD significantly decreased transcription of cyclin D1, a β-catenin target gene. Gamma-secretase inhibitors; presenilin-deficient cells; TAPI-1 alpha-secretase inhibitor; co-immunoprecipitation; in vitro cleavage; reporter gene assay for cyclin D1 transcription; immunoblotting for cleavage products The Journal of biological chemistry High 17259169
2009 NGL-3 (netrin-G ligand-3) interacts directly with LAR via a trans-synaptic interaction. NGL-3 and LAR expressed in heterologous cells induce pre- and postsynaptic differentiation bidirectionally in co-cultured hippocampal neurons. Knockdown of NGL-3 reduced excitatory synapse number and function. Competitive inhibition by soluble LAR reduced NGL-3-induced presynaptic differentiation, establishing the trans-synaptic NGL-3–LAR adhesion as regulating excitatory synapse formation. Co-culture synaptogenesis assay; heterologous cell expression; RNAi knockdown of NGL-3; soluble receptor competition; immunofluorescence; electrophysiology Nature neuroscience High 19252495
2009 Loss-of-function in both Ptprs and Ptprf (LAR) causes severe urogenital malformations (hydroureter, ureterocele) and craniofacial defects in mice. In cell culture, PTPσ (Ptprs) bound to and negatively regulated phosphorylation and signaling of the Ret receptor tyrosine kinase; Ret expression inhibited PTPσ-induced apoptosis. These results establish LAR family phosphatases as regulators of Ret-mediated apoptotic tissue morphogenesis during ureter maturation. Double knockout mice (Ptprs and Ptprf); histological and morphological analysis; cell culture binding and phosphorylation assays for Ret; apoptosis measurements The Journal of clinical investigation High 19273906
2010 The LRR domain of NGL-3 (nine LRRs) binds to the first two fibronectin III domains of LAR to induce bidirectional synapse formation. Gln-96 in the first LRR of NGL-3 is critical for LAR binding and presynaptic differentiation. PTPδ and PTPσ also bind NGL-3 via their first two FNIII domains with distinct synaptogenic outcomes. Domain-deletion and point mutation analysis; co-culture synaptogenesis assay; synapse induction quantification The Journal of biological chemistry High 20139422
2013 LAR dephosphorylates EphA2 specifically at phosphotyrosine 930, uncoupling Nck1 from EphA2 and attenuating EphA2-mediated cell migration. A siRNA screen of all human RPTPs identified EphA2 as a novel LAR substrate from a panel of 42 RTKs. siRNA screen of RPTPs; phosphorylation site-specific analysis (pY930 of EphA2); Nck1 co-immunoprecipitation; cell migration assay; site-directed mutagenesis Molecular and cellular biology High 23358419
2013 Slitrks interact with LAR-RPTP family members to regulate synapse formation; PTPσ is specifically required for excitatory synaptic differentiation by Slitrks, whereas PTPδ is required for inhibitory synapse differentiation. Slitrks are enriched in postsynaptic densities and their overexpression promotes, while RNAi knockdown decreases, synapse density. RNAi knockdown; overexpression; co-culture synaptogenesis assay; immunofluorescence; family-member-specific interaction analysis Proceedings of the National Academy of Sciences of the United States of America High 23345436
2013 miR-24 directly targets PTPRF (LAR) mRNA to suppress its expression, leading to elevated EGFR phosphorylation. Ectopic re-expression of PTPRF (LAR) decreased pEGFR levels, cell invasion and migration, and tumor metastasis in vivo, establishing LAR as a direct negative regulator of EGFR signaling in breast cancer cells. miRNA target validation; ectopic PTPRF overexpression; EGFR phosphorylation assays; cell invasion/migration assays; in vivo mouse tumor metastasis model Journal of cell science Medium 23418360
2014 Crystal structures of LAR-RPTP Ig1-3 in complex with Slitrk LRR1 reveal that splicing inserts in LAR-RPTP Ig domains are key molecular determinants for Slitrk binding and synapse formation. Unique properties on the concave surface of Slitrk1 LRR1 mediate specific binding to LAR-RPTPs. Lateral interactions between adjacent trans-synaptic LAR-RPTP/Slitrk complexes in crystal lattices are critical for higher-order assembly and synaptogenic activity. X-ray crystallography; structure-guided mutagenesis; co-culture synaptogenesis assay; biochemical binding assays Nature communications High 25394468
2015 SALM3 interacts with LAR-RPTPs (LAR, PTPσ, PTPδ) and this interaction requires the mini-exon B splice insert in LAR-RPTPs. SALM3-dependent presynaptic differentiation requires all three types of LAR-RPTPs. Salm3-knockout mice show markedly reduced excitatory synapse numbers in hippocampal CA1 and hypoactivity behavior, establishing SALM3–LAR-RPTP trans-synaptic adhesion as regulating excitatory synapse development. Biochemical binding assays; splice insert requirement analysis; co-culture synaptogenesis assay; Salm3 knockout mice; hippocampal synapse quantification; behavioral testing Cell reports High 26321637
2016 Loss of LAR phosphatase activity in mouse embryonic fibroblasts results in reduced focal adhesion numbers and decreased adhesion to fibronectin. Phosphoproteomic analysis identified CDK1 as a kinase regulated by LAR; LAR activity is required for CDK1 activity, and CDK1 activity is required for focal adhesion complex formation. LAR regulates CDK1 through c-Abl and Akt family proteins. Phosphatase-deficient LAR knock-in MEFs; phosphoproteomics; kinase prediction analysis; CDK1 activity assays; focal adhesion quantification; adhesion assays; pharmacological inhibition of CDK1, c-Abl, Akt Journal of cell science High 27352860
2017 Drosophila Lar (LAR ortholog) and Fat2 function in a planar signaling system at the basal domain of follicular epithelial cells to coordinate collective cell migration. Fat2 signals from each cell's trailing edge to stabilize Lar localization and induce leading-edge protrusions in the cell behind; Lar signals from the leading edge to stimulate trailing-edge retraction in the cell ahead. Fat2/Lar signaling mediates short-range communication between neighboring cells. Live imaging of Drosophila follicular epithelium; genetic loss-of-function; subcellular localization analysis; mosaic analysis Developmental cell High 28292425
2015 CSPGs signal through LAR and RPTPσ receptors in spinal cord neural precursor cells (NPCs) to inhibit growth, survival, proliferation, and oligodendrocyte differentiation. These inhibitory effects are mediated intracellularly through the Rho/ROCK pathway and inhibition of Akt and Erk1/2 phosphorylation. Genetic knockdown of LAR and RPTPσ, or blockade of ROCK, attenuates CSPG inhibition of NPCs. In vitro NPC cultures with CSPG substrate; genetic models (LAR/RPTPσ knockdown); Rho/ROCK inhibitors; Akt and Erk1/2 phosphorylation assays; proliferation and differentiation assays Stem cells High 25703008
2020 Crystal structure of LAR D1D2 in complex with SAM repeats of liprin-α3 reveals a conserved two-site binding mode. Liprin-αs promote LAR clustering in cells via the liprin-α/LAR interaction and liprin-α oligomerization. A unique homophilic D1/D1 interaction of LAR was identified; disruption of D1/D1 interaction diminishes liprin-α-promoted clustering and increases tyrosine dephosphorylation, establishing that LAR forms clusters in which phosphatase activity is negatively regulated. Additionally, LAR binding to liprin-α allosterically regulates the liprin-α/liprin-β interaction. X-ray crystallography; cellular clustering assays; mutagenesis of D1/D1 interface; tyrosine dephosphorylation assays; biochemical binding assays Nature communications High 31924785
2020 Conditional deletion of all three LAR-RPTPs (PTPδ, PTPσ, LAR) in mice did not affect synaptic connectivity or synapse number in vivo or in cultured neurons, but decreased NMDA receptor-mediated synaptic responses via a trans-synaptic mechanism without changing NMDA receptor protein levels or subunit composition. Conditional triple knockout mice (LAR-RPTPs); electrophysiology (AMPA- and NMDA-receptor EPSCs at Schaffer collateral synapses); protein level analysis; synapse counting in cultured neurons eLife High 31985401
2021 Superresolution microscopy reveals that PTPδ (a LAR-RPTP family member) localizes precisely to the synaptic cleft, apposed to postsynaptic scaffolds at both excitatory and inhibitory synapses. Triple conditional knockout of PTPδ, PTPσ, and LAR showed only mild effects on synaptic vesicle clustering and active zone architecture, with no effect on synapse number, membrane anchoring of the active zone, or vesicle docking and release. STORM/superresolution microscopy; triple-conditional knockout mice; electron microscopy; synaptic vesicle docking and release assays eLife High 33656439
2019 PPARγ directly binds to a consensus AGGTCA site in the PTPRF (LAR) promoter, demonstrated by electrophoretic mobility shift assay. PPARγ activation induces PTPRF expression, and ectopic PTPRF overexpression in breast cancer cells suppresses proliferation, migration, invasion, and colony formation, while a PTP inhibitor (NSC87877) abrogates PPARγ-mediated suppression, establishing PTPRF as a downstream effector of PPARγ tumor-suppressor activity. Electrophoretic mobility shift assay (EMSA); PPARγ overexpression/agonist treatment; PTPRF overexpression; PTP inhibitor (NSC87877); in vitro cell migration/invasion assays; in vivo mouse tumor model European review for medical and pharmacological sciences Medium 31799666
2013 Loss of both Ptprs and Ptprf (LAR) in mouse embryos leads to craniofacial malformations resembling Pierre-Robin sequence. Signaling analysis in embryonic tissues and MEFs identifies increased BMP-Smad signaling and abrogated canonical Wnt signaling in LAR family phosphatase-deficient cells. Chemical inhibition of GSK3β reactivates β-catenin signaling in deficient cells, establishing LAR-RPTPs as necessary for normal Wnt/β-catenin pathway activation. Double knockout mice; histological and cell proliferation analysis; Smad and β-catenin signaling pathway analysis; GSK3β inhibitor rescue in MEFs Development High 23863482
2020 Nrxn1α interacts with PTPσ (LAR-RPTP family) via heparan sulfate (HS)-dependent, high-affinity binding to Ig domains of PTPσ, regulated by PTPσ splicing status. Nrxn1α WT (but not ΔHS mutant lacking HS) inhibited PTPσ-mediated postsynapse-inducing activity at excitatory synapses and suppressed PTPσ-mediated maintenance of excitatory postsynaptic specializations. Drosophila epistasis of Dlar and Dnrx confirmed functional interactions controlling NMJ synapse formation and synaptic transmission. Biochemical binding assays; co-culture synaptogenesis assay; HS-deletion mutant analysis; hippocampal neuron imaging; Drosophila double-mutant epistasis at NMJ The Journal of neuroscience High 33037075
2018 Blocking LAR and PTPσ receptors in spinal cord injury reduces M1 microglia/macrophage populations while promoting M2 and T regulatory cells, and harnesses microglia phagocytosis and mobilization. CSPGs regulate microglia, at least in part, through the Rho/ROCK pathway downstream of LAR and PTPσ, establishing LAR as a mediator of CSPG-dependent neuroinflammation. Intrathecal peptide delivery (ILP/ISP blocking peptides); flow cytometry; immunohistochemistry; Western blotting; primary microglia in vitro cultures; Rho/ROCK pathway inhibition Journal of neuroinflammation Medium 29558941
2011 The SAM domain-containing cytoplasmic adaptor protein Caskin mediates LAR signal transduction during Drosophila motor axon guidance. Caskin physically interacts with LAR via its N-terminal SAM domain in vivo and in vitro. Caskin and Liprin-α do not bind LAR concurrently, suggesting they form distinct signaling complexes. The SH2/SH3 adaptor Dock is a second Caskin binding partner. A vertebrate Caskin homolog also interacts with LAR family members. Drosophila genetics; yeast two-hybrid and in vitro binding assays; genetic interaction/epistasis with LAR alleles; competition binding between Caskin and Liprin-α; vertebrate homolog interaction assays The Journal of neuroscience High 21430143

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains. Proceedings of the National Academy of Sciences of the United States of America 419 8643598
1990 Distinct functional roles of the two intracellular phosphatase like domains of the receptor-linked protein tyrosine phosphatases LCA and LAR. The EMBO journal 355 1695146
1995 The LAR transmembrane protein tyrosine phosphatase and a coiled-coil LAR-interacting protein co-localize at focal adhesions. The EMBO journal 293 7796809
1998 Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins. The Journal of biological chemistry 246 9624153
2013 Protein tyrosine phosphatases PTPδ, PTPσ, and LAR: presynaptic hubs for synapse organization. Trends in neurosciences 220 23835198
2005 LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses. Nature neuroscience 211 15750591
2006 The HSPGs Syndecan and Dallylike bind the receptor phosphatase LAR and exert distinct effects on synaptic development. Neuron 201 16476662
1995 The LAR/PTP delta/PTP sigma subfamily of transmembrane protein-tyrosine-phosphatases: multiple human LAR, PTP delta, and PTP sigma isoforms are expressed in a tissue-specific manner and associate with the LAR-interacting protein LIP.1. Proceedings of the National Academy of Sciences of the United States of America 188 8524829
2009 Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses. Nature neuroscience 179 19252495
1999 Rapid and irreversible inactivation of protein tyrosine phosphatases PTP1B, CD45, and LAR by peroxynitrite. Archives of biochemistry and biophysics 175 10486138
1990 Human globin locus activation region (LAR): role in temporal control. Trends in genetics : TIG 172 2202110
1992 Expression of the receptor-linked protein tyrosine phosphatase LAR: proteolytic cleavage and shedding of the CAM-like extracellular region. The EMBO journal 161 1547787
2012 Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study. Endocrine-related cancer 157 22807497
2013 Slitrks control excitatory and inhibitory synapse formation with LAR receptor protein tyrosine phosphatases. Proceedings of the National Academy of Sciences of the United States of America 155 23345436
1997 Cellular redistribution of protein tyrosine phosphatases LAR and PTPsigma by inducible proteolytic processing. The Journal of cell biology 143 9245795
2013 LAR-RPTPs: synaptic adhesion molecules that shape synapse development. Trends in cell biology 141 23916315
1991 Cloning, bacterial expression, purification, and characterization of the cytoplasmic domain of rat LAR, a receptor-like protein tyrosine phosphatase. The Journal of biological chemistry 138 1918076
1995 Insulin receptor signaling is augmented by antisense inhibition of the protein tyrosine phosphatase LAR. The Journal of biological chemistry 136 7852302
2004 Functional significance of the LAR receptor protein tyrosine phosphatase family in development and diseases. Biochemistry and cell biology = Biochimie et biologie cellulaire 134 15674434
2001 Drosophila LAR regulates R1-R6 and R7 target specificity in the visual system. Neuron 131 11683994
2013 MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling. Journal of cell science 130 23418360
2001 The receptor-like tyrosine phosphatase lar is required for epithelial planar polarity and for axis determination within drosophila ovarian follicles. Development (Cambridge, England) 128 11688569
2010 Trans-synaptic adhesions between netrin-G ligand-3 (NGL-3) and receptor tyrosine phosphatases LAR, protein-tyrosine phosphatase delta (PTPdelta), and PTPsigma via specific domains regulate excitatory synapse formation. The Journal of biological chemistry 126 20139422
1997 Impaired mammary gland development and function in mice lacking LAR receptor-like tyrosine phosphatase activity. Developmental biology 120 9245518
1996 The transmembrane protein-tyrosine phosphatase LAR modulates signaling by multiple receptor tyrosine kinases. The Journal of biological chemistry 117 8557682
2009 Expression analysis of dopamine receptor subtypes in normal human pituitaries, nonfunctioning pituitary adenomas and somatotropinomas, and the association between dopamine and somatostatin receptors with clinical response to octreotide-LAR in acromegaly. The Journal of clinical endocrinology and metabolism 116 19293270
1995 Increased abundance of the receptor-type protein-tyrosine phosphatase LAR accounts for the elevated insulin receptor dephosphorylating activity in adipose tissue of obese human subjects. The Journal of clinical investigation 112 7769120
2001 Cell-autonomous and -nonautonomous functions of LAR in R7 photoreceptor axon targeting. Neuron 111 11683993
1997 Deficient LAR expression decreases basal forebrain cholinergic neuronal size and hippocampal cholinergic innervation. Journal of neuroscience research 103 9039657
2001 Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance. Proceedings of the National Academy of Sciences of the United States of America 100 11309481
1998 Transgenic mice deficient in the LAR protein-tyrosine phosphatase exhibit profound defects in glucose homeostasis. Diabetes 99 9519761
2014 Structural basis for LAR-RPTP/Slitrk complex-mediated synaptic adhesion. Nature communications 98 25394468
2017 Fat2 and Lar Define a Basally Localized Planar Signaling System Controlling Collective Cell Migration. Developmental cell 94 28292425
1997 Functional association between the insulin receptor and the transmembrane protein-tyrosine phosphatase LAR in intact cells. The Journal of biological chemistry 91 8995282
2018 Perturbing chondroitin sulfate proteoglycan signaling through LAR and PTPσ receptors promotes a beneficial inflammatory response following spinal cord injury. Journal of neuroinflammation 85 29558941
1995 LAR tyrosine phosphatase receptor: alternative splicing is preferential to the nervous system, coordinated with cell growth and generates novel isoforms containing extensive CAG repeats. The Journal of cell biology 83 7844155
2007 Liprinalpha1 degradation by calcium/calmodulin-dependent protein kinase II regulates LAR receptor tyrosine phosphatase distribution and dendrite development. Developmental cell 81 17419996
2007 LAR, liprin alpha and the regulation of active zone morphogenesis. Journal of cell science 72 17959628
1996 Modulation of insulin signal transduction by eutopic overexpression of the receptor-type protein-tyrosine phosphatase LAR. Molecular endocrinology (Baltimore, Md.) 68 8732688
1994 Mutational analysis of proprotein processing, subunit association, and shedding of the LAR transmembrane protein tyrosine phosphatase. The Journal of biological chemistry 65 8089133
2015 Chondroitin Sulfate Proteoglycans Negatively Modulate Spinal Cord Neural Precursor Cells by Signaling Through LAR and RPTPσ and Modulation of the Rho/ROCK Pathway. Stem cells (Dayton, Ohio) 64 25703008
2015 Splicing-Dependent Trans-synaptic SALM3-LAR-RPTP Interactions Regulate Excitatory Synapse Development and Locomotion. Cell reports 64 26321637
2004 Treatment of ECL cell carcinoids with octreotide LAR. Scandinavian journal of gastroenterology 64 15370681
2009 Acromegaly: correlation between expression of somatostatin receptor subtypes and response to octreotide-lar treatment. Pituitary 63 19330452
2007 The tumor suppressor DAPK is reciprocally regulated by tyrosine kinase Src and phosphatase LAR. Molecular cell 63 17803936
1992 Catalytic domains of the LAR and CD45 protein tyrosine phosphatases from Escherichia coli expression systems: purification and characterization for specificity and mechanism. Biochemistry 63 1370625
1998 Developmental expression of the cell adhesion molecule-like protein tyrosine phosphatases LAR, RPTPdelta and RPTPsigma in the mouse. Mechanisms of development 62 9784606
1991 Isolation and characterization of temperature-sensitive and thermostable mutants of the human receptor-like protein tyrosine phosphatase LAR. The Journal of biological chemistry 58 1645351
2016 SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development. Scientific reports 57 27225731
2009 Maturation of ureter-bladder connection in mice is controlled by LAR family receptor protein tyrosine phosphatases. The Journal of clinical investigation 56 19273906
1994 Genomic organization of the human LAR protein tyrosine phosphatase gene and alternative splicing in the extracellular fibronectin type-III domains. The Journal of biological chemistry 55 7929208
1999 Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas. Genes to cells : devoted to molecular & cellular mechanisms 53 10320483
2021 Nomogram Based on Lactate Dehydrogenase-to-Albumin Ratio (LAR) and Platelet-to-Lymphocyte Ratio (PLR) for Predicting Survival in Nasopharyngeal Carcinoma. Journal of inflammation research 52 34447260
2014 Role of CSPG receptor LAR phosphatase in restricting axon regeneration after CNS injury. Neurobiology of disease 52 25220840
1998 Overexpression of the transmembrane tyrosine phosphatase LAR activates the caspase pathway and induces apoptosis. Current biology : CB 52 9501065
2007 Presenilin/gamma-secretase-mediated cleavage regulates association of leukocyte-common antigen-related (LAR) receptor tyrosine phosphatase with beta-catenin. The Journal of biological chemistry 51 17259169
2020 LAR receptor phospho-tyrosine phosphatases regulate NMDA-receptor responses. eLife 50 31985401
2002 The C. elegans LAR-like receptor tyrosine phosphatase PTP-3 and the VAB-1 Eph receptor tyrosine kinase have partly redundant functions in morphogenesis. Development (Cambridge, England) 50 11959824
2018 LAR and PTPσ receptors are negative regulators of oligodendrogenesis and oligodendrocyte integrity in spinal cord injury. Glia 47 30394599
2006 Contact inhibition of hepatocyte growth regulated by functional association of the c-Met/hepatocyte growth factor receptor and LAR protein-tyrosine phosphatase. The Journal of biological chemistry 47 16415345
2021 Pegvisomant and Pasireotide LAR as second line therapy in acromegaly: clinical effectiveness and predictors of response. European journal of endocrinology 45 33136550
2006 LAR protein tyrosine phosphatase receptor associates with TrkB and modulates neurotrophic signaling pathways. Journal of neurobiology 45 17013927
2016 Emergent Synapse Organizers: LAR-RPTPs and Their Companions. International review of cell and molecular biology 44 27017006
2009 Octreotide LAR: safety and tolerability issues. Expert opinion on drug safety 44 19998528
1996 Suppression of insulin receptor activation by overexpression of the protein-tyrosine phosphatase LAR in hepatoma cells. Cellular signalling 44 9023010
2006 Liprin-alpha has LAR-independent functions in R7 photoreceptor axon targeting. Proceedings of the National Academy of Sciences of the United States of America 43 16864797
1998 LAR tyrosine phosphatase receptor: a developmental isoform is present in neurites and growth cones and its expression is regional- and cell-specific. Molecular and cellular neurosciences 43 9604206
1997 Inter- and intraspecific variation in the diets of sympatric siamang (Hylobates syndactylus) and lar gibbons (Hylobates lar). Folia primatologica; international journal of primatology 43 9375367
2005 Identification of an ectodomain within the LAR protein tyrosine phosphatase receptor that binds homophilically and activates signalling pathways promoting neurite outgrowth. The European journal of neuroscience 42 16262654
2006 EGFR signaling leads to downregulation of PTP-LAR via TACE-mediated proteolytic processing. Cellular signalling 41 16478662
2018 Role of extracellular matrix and microenvironment in regulation of tumor growth and LAR-mediated invasion in glioblastoma. PloS one 40 30286133
2021 LAR Receptor Tyrosine Phosphatase Family in Healthy and Diseased Brain. Frontiers in cell and developmental biology 39 34966732
2019 How to Position Pasireotide LAR Treatment in Acromegaly. The Journal of clinical endocrinology and metabolism 39 30608534
2018 Treatment of multiresistant prolactinomas with a combination of cabergoline and octreotide LAR. Endocrine 39 29948930
1992 Purification and characterization of the catalytic domains of the human receptor-linked protein tyrosine phosphatases HPTP beta, leukocyte common antigen (LCA), and leukocyte common antigen-related molecule (LAR). The Journal of biological chemistry 39 1318316
2001 Distinct functions of the two protein tyrosine phosphatase domains of LAR (leukocyte common antigen-related) on tyrosine dephosphorylation of insulin receptor. Molecular endocrinology (Baltimore, Md.) 37 11158333
2020 Structural basis of liprin-α-promoted LAR-RPTP clustering for modulation of phosphatase activity. Nature communications 36 31924785
2009 The receptor protein tyrosine phosphatase LAR promotes R7 photoreceptor axon targeting by a phosphatase-independent signaling mechanism. Proceedings of the National Academy of Sciences of the United States of America 36 19889974
2004 Mice lacking leukocyte common antigen-related (LAR) protein tyrosine phosphatase domains demonstrate spatial learning impairment in the two-trial water maze and hyperactivity in multiple behavioural tests. Behavioural brain research 36 15302123
2000 Downregulation of LAR tyrosine phosphatase prevents apoptosis and augments NGF-induced neurite outgrowth. Journal of neurobiology 36 10699984
2011 The cytoplasmic adaptor protein Caskin mediates Lar signal transduction during Drosophila motor axon guidance. The Journal of neuroscience : the official journal of the Society for Neuroscience 35 21430143
2020 LAR-RPTPs Directly Interact with Neurexins to Coordinate Bidirectional Assembly of Molecular Machineries. The Journal of neuroscience : the official journal of the Society for Neuroscience 34 33037075
2012 LAR receptor tyrosine phosphatases and HSPGs guide peripheral sensory axons to the skin. Current biology : CB 34 22326027
1997 The protein tyrosine phosphatase LAR has a major impact on insulin receptor dephosphorylation. Biochemical and biophysical research communications 34 9207225
2016 SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion. Nature communications 29 27480238
2012 The receptor tyrosine phosphatase Lar regulates adhesion between Drosophila male germline stem cells and the niche. Development (Cambridge, England) 29 22378638
2004 Stimulated regeneration of the crushed adult rat optic nerve correlates with attenuated expression of the protein tyrosine phosphatases RPTPalpha, STEP, and LAR. Molecular and cellular neurosciences 29 15555919
2021 Glucose metabolism outcomes in acromegaly patients on treatment with pasireotide-LAR or pasireotide-LAR plus Pegvisomant. Endocrine 27 33907985
2019 Pasireotide-LAR in acromegaly patients treated with a combination therapy: a real-life study. Endocrine connections 27 31518993
2016 LAR protein tyrosine phosphatase regulates focal adhesions through CDK1. Journal of cell science 27 27352860
2010 Octreotide long-acting release (LAR): a review of its use in the management of acromegaly. Drugs 27 20731479
2002 Expression of the leucocyte common antigen-related (LAR) tyrosine phosphatase is regulated by cell density through functional E-cadherin complexes. The Biochemical journal 27 12095414
2019 PPARγ inhibits breast cancer progression by upregulating PTPRF expression. European review for medical and pharmacological sciences 26 31799666
2013 Receptor protein tyrosine phosphatase-receptor tyrosine kinase substrate screen identifies EphA2 as a target for LAR in cell migration. Molecular and cellular biology 26 23358419
2013 Inactivation of LAR family phosphatase genes Ptprs and Ptprf causes craniofacial malformations resembling Pierre-Robin sequence. Development (Cambridge, England) 26 23863482
2021 Intact synapse structure and function after combined knockout of PTPδ, PTPσ, and LAR. eLife 25 33656439
2017 LAR-RPTP Clustering Is Modulated by Competitive Binding between Synaptic Adhesion Partners and Heparan Sulfate. Frontiers in molecular neuroscience 25 29081732
2000 Expression of CRYP-alpha, LAR, PTP-delta, and PTP-rho in the developing Xenopus visual system. Mechanisms of development 25 10727868
2022 Suppressing CSPG/LAR/PTPσ Axis Facilitates Neuronal Replacement and Synaptogenesis by Human Neural Precursor Grafts and Improves Recovery after Spinal Cord Injury. The Journal of neuroscience : the official journal of the Society for Neuroscience 24 35256527
2022 Luminal androgen receptor (LAR) subtype of triple-negative breast cancer: molecular, morphological, and clinical features. Journal of Zhejiang University. Science. B 24 35953756

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