Affinage

PDPN

Podoplanin · UniProt Q86YL7

Round 2 corrected
Length
162 aa
Mass
16.7 kDa
Annotated
2026-04-29
130 papers in source corpus 24 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Podoplanin (PDPN) is a mucin-type transmembrane glycoprotein that couples extracellular glycan-mediated receptor engagement to intracellular cytoskeletal remodeling, thereby governing platelet activation, cell motility, and tissue morphogenesis. Its extracellular sialylated O-glycan PLAG domains (centered on Thr34/Thr52) engage the platelet C-type lectin receptor CLEC-2 to induce platelet aggregation, a function essential for developmental blood–lymphatic vascular separation, hematogenous metastasis, megakaryocyte subtype polarization, and inflammatory signaling upon UGRP1 co-ligation (PMID:14522983, PMID:17616532, PMID:20110424, PMID:39615442, PMID:35652821). The short cytoplasmic tail binds ERM proteins (ezrin/moesin) via juxtamembrane basic residues to activate RhoA, driving epithelial–mesenchymal transition, filopodia-based collective invasion, and osteocyte dendrite elongation; PKA and CDK5 phosphorylate two conserved intracellular serines to inhibit this motility program (PMID:17046996, PMID:16616332, PMID:16738320, PMID:25959509). PDPN function is modulated by CD9, which suppresses CLEC-2 engagement via transmembrane domain interaction, by CD177, which acts as an extracellular antagonist on cancer-associated fibroblasts, and by calpain-1-mediated proteolytic turnover (PMID:18541721, PMID:34879110, PMID:19146981).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Establishing that PDPN is a membrane glycoprotein concentrated at actin-rich protrusions that physically associates with ERM proteins and remodels the cytoskeleton answered the foundational question of where PDPN acts and what immediate intracellular partners it engages.

    Evidence Co-immunoprecipitation of ezrin/moesin with PA2.26, confocal/immunoelectron microscopy in keratinocytes with ectopic expression

    PMID:10574709

    Open questions at the time
    • Direct binding site on PDPN not mapped
    • RhoA pathway not yet implicated
    • No glycan function addressed
  2. 2003 High

    Identification of the PLAG domain with its O-glycosylated Thr34/Thr52 as the critical determinant for platelet aggregation revealed the extracellular functional module of PDPN and established a mechanistic basis for its thrombogenic activity.

    Evidence Purified Aggrus/PDPN from CHO cells, point mutagenesis of PLAG threonines, platelet aggregation assay

    PMID:14522983

    Open questions at the time
    • Platelet receptor not yet identified
    • In vivo relevance to metastasis untested
  3. 2004 High

    Demonstrating that sialylated core 1 O-glycans—but not N-glycans—are required for platelet aggregation defined the glycan code that activates the platelet interaction, narrowing the molecular requirements for PLAG domain function.

    Evidence Expression in CHO glycosylation-deficient mutant lines (Lec1/Lec2/Lec8), lectin blotting, platelet aggregation

    PMID:15231832

    Open questions at the time
    • Identity of the platelet-side receptor still unknown
    • Structural basis of glycan recognition unresolved
  4. 2006 High

    Mapping the ERM-binding site to juxtamembrane basic residues and showing this interaction is required for RhoA activation and EMT established the signaling axis downstream of PDPN's cytoplasmic tail, while parallel work demonstrated PDPN drives collective invasion via modulation of Rho GTPases even without full EMT.

    Evidence In vitro pull-down/co-IP with cytoplasmic tail mutants, RhoA activity assays, dominant-negative ezrin/RhoA epistasis in MDCK cells; Rho GTPase assays and invasion assays in breast cancer cells and mouse pancreatic carcinogenesis

    PMID:16616332 PMID:17046996

    Open questions at the time
    • Relative contributions of RhoA activation vs. other Rho family members unclear
    • Structural basis of ERM–PDPN binding unresolved
  5. 2006 High

    Showing that PDPN/E11 is required for osteocyte dendrite elongation under mechanical shear stress extended PDPN's cytoskeletal function beyond cancer to a physiological mechanosensory context.

    Evidence siRNA knockdown in MLO-Y4 osteocyte-like cells, fluid flow shear stress assays, in vivo mechanical loading

    PMID:16738320

    Open questions at the time
    • Downstream signaling pathway in osteocytes not fully delineated
    • Whether ERM binding is required for dendricity not tested
  6. 2007 High

    Identification of CLEC-2 as the platelet receptor for PDPN and demonstration that their sialic acid-dependent interaction triggers Src/PLCγ2 signaling on platelets resolved the receptor–ligand pair governing PDPN-induced platelet activation, while in vivo mutagenesis of PLAG Thr34/Thr52 proved this axis drives pulmonary metastasis.

    Evidence Flow cytometry binding, recombinant CLEC-2 inhibition of platelet aggregation, Src/PLCγ2 inhibitor studies; PLAG point mutant cells in experimental metastasis mouse models with intravital imaging

    PMID:17392172 PMID:17616532

    Open questions at the time
    • Crystal structure of PDPN–CLEC-2 complex not available
    • Whether CLEC-2 is the sole platelet receptor not excluded
  7. 2008 High

    Discovery that CD9 complexes with PDPN through its transmembrane domains and suppresses CLEC-2-dependent platelet aggregation and metastasis identified the first negative cis-regulator of PDPN, while calpain-1 was shown to mediate PDPN proteolytic turnover, revealing a second layer of post-translational control.

    Evidence Reciprocal co-IP, TM domain deletion mutagenesis, platelet aggregation and metastasis assays; in vitro calpain-1 cleavage, calpain inhibitor accumulation studies

    PMID:18541721 PMID:19146981

    Open questions at the time
    • Structural detail of CD9–PDPN TM interaction unknown
    • Calpain cleavage site on PDPN not mapped
    • Physiological triggers of calpain-mediated PDPN turnover undefined
  8. 2010 High

    Genetic and pharmacological ablation of PDPN–CLEC-2 signaling in mouse embryos producing blood-filled lymphatics established the physiological requirement for this axis in blood–lymphatic vascular separation during development.

    Evidence Podoplanin-knockout embryos, blocking antibodies, aspirin treatment, kindlin-3 KO; immunohistochemistry of platelet aggregates at separation zone

    PMID:20110424

    Open questions at the time
    • Downstream lymphatic-intrinsic signaling consequences not addressed
    • Whether platelet aggregation is sufficient or other PDPN functions contribute is unclear
  9. 2013 High

    Demonstrating that PKA phosphorylates the two conserved intracellular serines of PDPN to inhibit motility—on a Pdpn-null background—defined a kinase-dependent off-switch for PDPN-driven migration, later extended to CDK5 cooperation.

    Evidence In vitro PKA and CDK5 kinase assays, phosphomimetic/non-phosphorylatable mutagenesis on Pdpn-null MEFs, migration assays

    PMID:23530051 PMID:25959509

    Open questions at the time
    • In vivo phosphorylation stoichiometry unknown
    • Phosphatase that reverses this modification not identified
  10. 2012 Medium

    Identification of IMP-3/IGF2BP3 as a stabilizer of PDPN mRNA via its 3′UTR revealed a post-transcriptional regulatory layer that sustains PDPN levels required for invadopodia formation and extracellular matrix degradation.

    Evidence 3′UTR luciferase reporter, RNA in situ hybridization, siRNA knockdown with invasion and xenograft readouts in oral SCC cells

    PMID:22859271

    Open questions at the time
    • Exact IMP-3 binding site in PDPN 3′UTR not mapped
    • Other RNA-binding proteins that regulate PDPN mRNA not explored
  11. 2021 Medium

    High-throughput interactome screening identified CD177 as an extracellular antagonist of PDPN on cancer-associated fibroblasts, phenocopying PDPN loss and revealing a trans-cellular regulatory mechanism in the tumor stroma.

    Evidence Extracellular interactome screen, quantitative phosphoproteomics of PDPN-deficient CAFs, functional assays with recombinant CD177

    PMID:34879110

    Open questions at the time
    • Binding interface between CD177 and PDPN not mapped
    • Physiological relevance in non-tumor contexts untested
    • Single-lab finding awaiting independent replication
  12. 2022 Medium

    Showing that UGRP1 binds PDPN to activate RhoA–NF-κB signaling and amplify innate immune receptor expression in macrophages during pneumococcal infection extended PDPN function to inflammatory innate immunity beyond its established roles in platelets and motility.

    Evidence Co-IP of UGRP1–PDPN, RhoA activity assay, NF-κB reporter, siRNA/antibody blocking, in vivo mouse pneumonia model with RhoA agonist rescue

    PMID:35652821

    Open questions at the time
    • Whether PDPN on macrophages signals via ERM in this context not tested
    • Specificity of UGRP1 for PDPN versus other receptors not fully excluded
  13. 2024 Medium

    Recent work revealed that PDPN–CLEC-2 signaling directs megakaryocyte subtype differentiation and that PDPN activates Wnt/β-catenin to upregulate PD-L1, linking PDPN to hematopoietic lineage decisions and immune evasion.

    Evidence PDPN-KO and CLEC-2-cKO co-culture systems with megakaryocyte progenitors; β-catenin/PD-L1 Western blotting, CD8+ T-cell depletion epistasis in melanoma models

    PMID:38167452 PMID:39615442

    Open questions at the time
    • Wnt/β-catenin activation mechanism by PDPN not elucidated at the molecular level
    • Whether megakaryocyte subtype polarization occurs in vivo in bone marrow niches not confirmed
    • Structural basis of PDPN antagonist peptide CY12-RP2 binding unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structure of the PDPN–CLEC-2 complex, how PDPN simultaneously engages ERM proteins and activates distinct downstream pathways (RhoA, Wnt/β-catenin, NF-κB) in different cell types, and the identity of phosphatases that reverse PKA/CDK5-mediated inhibition of PDPN motility function.
  • No high-resolution structure of PDPN or its complexes
  • Cell-type-specific signaling logic downstream of PDPN not resolved
  • Calpain cleavage site and degradation kinetics in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098631 cell adhesion mediator activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 3
Pathway
R-HSA-109582 Hemostasis 6 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 2 R-HSA-168256 Immune System 2
Partners
CAPN1CD177CD9CLEC2EZRIGF2BP3MSNUGRP1
Complex memberships
PDPN–CD9 complexPDPN–ERM complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 PA2.26 (podoplanin/PDPN) is a mucin-like transmembrane glycoprotein concentrated in actin-rich microvilli and plasma membrane projections (filopodia, lamellipodia, ruffles) where it co-localizes with ERM family proteins; ezrin and moesin (but not radixin) co-immunoprecipitate with PA2.26. Ectopic expression in keratinocytes induces fibroblastoid morphological conversion, major actin cytoskeleton reorganization, redistribution of ezrin to cell-surface projections, and enhanced motility. Co-immunoprecipitation, confocal/immunoelectron microscopy, ectopic expression in keratinocytes with phenotypic readout Journal of cell science High 10574709
2003 Aggrus/podoplanin (PDPN) is a platelet aggregation-inducing sialoglycoprotein; its platelet aggregation-stimulating (PLAG) domain containing O-glycosylated threonine residues (Thr34 and Thr52) is the critical determinant for platelet aggregation-inducing activity. Purified Aggrus induces platelet aggregation without requiring plasma components. Antibody-affinity purification of native protein, expression in CHO cells, point mutagenesis of PLAG domain threonines, platelet aggregation assay The Journal of biological chemistry High 14522983
2004 Sialylated O-glycans (specifically sialic acid plus Gal-β1,3-GalNAc-Ser/Thr, i.e., sialylated core 1 structure) on Aggrus/podoplanin are critical for its platelet aggregation-inducing activity. CMP-sialic acid transporter-deficient and UDP-galactose transporter-deficient CHO cells expressing Aggrus lost platelet aggregation activity, while N-glycan-deficient cells retained it. Stable expression in CHO glycosylation-deficient mutant cell lines (Lec1, Lec2, Lec8), lectin blotting, platelet aggregation assay The Journal of biological chemistry High 15231832
2005 Human PA2.26/podoplanin co-localizes with ezrin at the surface of tumor cells and its presence in oral squamous cell carcinoma is associated with downregulation of membrane E-cadherin. Ectopic expression in HeLa and HaCaT cells promotes redistribution of ezrin to cell edges, formation of cell-surface protrusions, and reduced Ca2+-dependent cell-cell adhesiveness. Double immunofluorescence, confocal microscopy, ectopic expression with phenotypic readouts (protrusion formation, adhesion assay) International journal of cancer Medium 15515019
2006 E11/gp38 (podoplanin/PDPN) is selectively expressed in osteocytes and is required for dendrite elongation; fluid flow shear stress increases E11 mRNA in osteocyte-like cells (MLO-Y4), and siRNA knockdown of E11 blocks shear stress-induced dendricity and dendrite elongation. siRNA knockdown, fluid flow shear stress assay, MLO-Y4 osteocyte-like cell culture, in vivo mechanical loading Molecular and cellular biology High 16738320
2006 Podoplanin directly interacts in vitro and in vivo with ezrin (and moesin) through a cluster of basic amino acids within its cytoplasmic tail, primarily through the juxtamembrane dipeptide RK. This interaction is required for podoplanin-induced RhoA activation and epithelial-mesenchymal transition (EMT) in MDCK cells. Dominant-negative truncated ezrin or dominant-negative RhoA blocked these effects. In vitro pull-down, co-immunoprecipitation, GFP-tagged cytoplasmic tail mutants, RhoA activity assay (pull-down), dominant-negative constructs, fluorescence time-lapse video microscopy Journal of cell science High 17046996
2006 Podoplanin promotes tumor cell invasion via downregulation of small Rho family GTPase activities leading to filopodia formation and collective cell migration, in a manner that does not require epithelial-mesenchymal transition (E-cadherin expression maintained). Overexpression in cultured human breast cancer cells, mouse pancreatic beta-cell carcinogenesis model, Rho GTPase activity assays, in vitro invasion assays, human cancer biopsy analysis Cancer cell High 16616332
2006 The PLAG (platelet aggregation-stimulating) domain of Aggrus/podoplanin is conserved across mammalian species with three tandem repeats; the first or last (but not middle) PLAG domain is critical for platelet aggregation-inducing activity. Bovine Aggrus with a deletion in the first PLAG domain lacks platelet aggregation activity. Point mutations in PLAG domains confirmed their functional importance. Cross-species cDNA cloning, point mutagenesis, platelet aggregation assay, phylogenetic analysis Gene High 16766141
2007 PDPN/Aggrus promotes pulmonary metastasis by inducing platelet aggregation via its PLAG domain (specifically Thr34 and Thr52); point mutation at these residues abolishes both platelet aggregation and metastasis. Aggrus-expressing cells become covered with platelets and arrest in lung microvasculature within 30 minutes post-injection. Point mutagenesis, experimental and spontaneous metastasis mouse models, intravital observation of platelet-tumor cell interactions, aspirin treatment The American journal of pathology High 17392172
2007 CLEC-2 is identified as the platelet receptor for podoplanin; their association is sialic acid-dependent (on O-glycans of podoplanin). Recombinant CLEC-2 inhibits platelet aggregation induced by podoplanin-expressing tumor cells or lymphatic endothelial cells, and CLEC-2-mediated signaling involves Src and phospholipase Cγ2 activation. Flow cytometry binding assay, recombinant CLEC-2 inhibition of platelet aggregation, signaling inhibitor studies (Src, PLCγ2) The Journal of biological chemistry High 17616532
2008 CD9 (tetraspanin) forms a complex with Aggrus/podoplanin via transmembrane domains 1 and 2 (TM1 and TM2) of CD9. CD9 and Aggrus interact homophilically and co-localize in low-density membrane fractions. CD9 expression suppresses Aggrus-induced platelet aggregation and metastasis; deletion of TM1 and TM2 abolishes these inhibitory effects. Co-immunoprecipitation, low-density membrane fractionation, TM domain deletion constructs, platelet aggregation assay, experimental metastasis model Blood High 18541721
2008 Podoplanin expression is regulated post-translationally by calpain-mediated proteolysis; calpain-1 cleaves podoplanin in vitro, and calpain inhibition leads to podoplanin accumulation in tumor cells that transcribe but do not accumulate podoplanin protein. A novel podoplanin isoform lacking the cytoplasmic YS dipeptide (generated by alternative splicing) was identified; this YS motif is highly conserved across species. Western blot with protease inhibitors (calpeptin, lactacystin), in vitro calpain-1 cleavage assay, alternative splicing analysis The international journal of biochemistry & cell biology High 19146981
2010 Podoplanin on lymphatic endothelial cells activates circulating platelets from the cardinal vein via CLEC-2 interaction, and this platelet activation is required for separation of the lymphatic from the blood vascular system during embryonic development. Platelet aggregates form at the separation zone in wild-type but not podoplanin-knockout embryos; the same blood-filled lymphatic phenotype is induced by podoplanin-blocking antibodies, aspirin, or kindlin-3 knockout (which impairs platelet aggregation). Podoplanin knockout mouse embryo analysis, aspirin treatment of pregnant mice, podoplanin-blocking antibody administration, kindlin-3 knockout, immunohistochemistry of embryonic platelet aggregates Blood High 20110424
2012 IMP-3 (IGF2BP3) stabilizes PDPN mRNA through binding to the 3'UTR of PDPN, maintaining podoplanin levels required for functional invadopodia formation and extracellular matrix degradation in oral squamous cell carcinoma cells. IMP-3 depletion reduces PDPN mRNA stability and abolishes invadopodia-mediated ECM degradation. TGF-β1 increases PDPN expression, potentiating cancer invasion via invadopodia. RNA in situ hybridization with 3'UTR probe, luciferase reporter assay with PDPN 3'UTR, siRNA knockdown, Transwell invasion assay, xenograft model Carcinogenesis Medium 22859271
2013 The two conserved intracellular serine residues of podoplanin (PDPN) can be phosphorylated by PKA (protein kinase A). Conversion of these serines to non-phosphorylatable alanines enhances cell migration, while conversion to phosphomimetic aspartates decreases cell migration, indicating that PKA-mediated phosphorylation of PDPN inhibits cell motility. PDPN expression in fibroblasts facilitates motility and viability of neighboring melanoma cells in co-culture. Knockout MEFs from Pdpn-null mice, site-directed mutagenesis (Ser→Ala and Ser→Asp), in vitro PKA phosphorylation assay, migration assays, co-culture experiments The Journal of biological chemistry High 23530051
2013 Aggrus/podoplanin promotes tumor growth in addition to metastasis through platelet-tumor interaction, platelet activation, and secretion of platelet-derived factors in vivo. Aggrus knockdown suppressed platelet-induced proliferation in vitro and tumor growth in vivo. The anti-Aggrus monoclonal antibody MS-1 suppresses Aggrus-CLEC-2 binding, platelet aggregation, and metastasis, and exhibits ADCC and CDC activities against Aggrus-positive tumors. siRNA knockdown, in vitro platelet co-culture proliferation assay, xenograft tumor growth model, antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity assays PloS one Medium 23991201
2015 Both PKA and CDK5 phosphorylate podoplanin (PDPN) on its two conserved intracellular serine residues, and they cooperate to phosphorylate both serines to decrease cell motility. CDK5 phosphorylation of PDPN was demonstrated in addition to the previously characterized PKA phosphorylation. In vitro kinase assays with PKA and CDK5, site-directed mutagenesis of intracellular serines, cell migration assays Experimental cell research High 25959509
2019 PDPN induces phosphorylation of ERM (ezrin, radixin, moesin) proteins and is associated with expression and activity of MMP-2 and MMP-9, actin cytoskeleton remodeling, and cellular protrusion formation in thyroid carcinoma cells. Inhibition of the MAPK pathway (with U0126 or PLX4720) decreases PDPN expression and increases E/R/M phosphorylation, reducing cell migration. siRNA knockdown of PDPN, Western blotting for ERM phosphorylation, gelatin zymography for MMP activity, scratch and Transwell migration/invasion assays, MAPK pathway inhibitors BMC cancer Medium 30654768
2021 CD177 (neutrophil protein) is identified as a novel binding partner/receptor of PDPN on cancer-associated fibroblasts using a high-throughput cell surface interactome screen. CD177 acts as a functional antagonist of PDPN, recapitulating the phenotype of PDPN-deficient CAFs. Quantitative phosphoproteomics of PDPN-deficient CAFs reveals PDPN regulates cell signaling, growth, and actomyosin contractility. High-throughput extracellular interactome screen, quantitative phosphoproteomics (MS), cellular assays with PDPN-deficient CAFs and CD177 treatment PloS one Medium 34879110
2022 UGRP1 binds to cell-surface PDPN and activates RhoA, enhancing interaction of IKKγ and IKKβ to slightly activate NF-κB, which upregulates expression of TLR2, MyD88, NOD2, and NLRP3, thereby promoting inflammatory cytokine production (IL-6, IL-1β, TNF-α) in macrophages during Streptococcus pneumoniae infection. Blocking UGRP1-PDPN interaction protected mice from severe pneumococcal pneumonia. Co-immunoprecipitation (UGRP1-PDPN binding), RhoA activation assay, NF-κB reporter/Western blot, siRNA/antibody blocking, in vivo mouse infection model with RhoA agonist rescue Clinical and translational medicine Medium 35652821
2024 The PDPN/CLEC-2 axis modulates megakaryocyte subtype differentiation; stromal PDPN interacting with CLEC-2 on megakaryocyte progenitors drives differentiation toward MYLK4-positive HSC-regulating megakaryocytes (with higher ploidy) at the expense of BMAL1-positive platelet-producing megakaryocytes, thus increasing megakaryocyte number while decreasing platelet output. Co-culture of hematopoietic progenitors with PDPN-expressing or PDPN-knockout immortalized stromal feeder cells, CLEC-2 conditional KO megakaryocytes, flow cytometry for megakaryocyte subtype markers and ploidy Thrombosis research Medium 39615442
2024 MMP13 upregulates PDPN expression in endothelial cells, and PDPN mediates the platelet aggregation-promoting effect of MMP13 in HUVECs; PDPN-siRNA knockdown attenuates MMP13-induced platelet aggregation. In a DVT mouse model, MMP13 inhibition reduces PDPN expression and decreases deep vein thrombosis burden. MMP13 overexpression and siRNA knockdown in HUVECs, PDPN-siRNA knockdown, platelet aggregation assay, in vivo DVT mouse model with transcriptome analysis Current medical science Medium 38619683
2024 PDPN promotes melanoma cell growth and metastasis through activation of the Wnt/β-catenin pathway, and this pathway also mediates PDPN-dependent upregulation of PD-L1. A PDPN antagonist peptide (CY12-RP2) suppresses these effects, reduces tumor growth, restores CD8+ T-cell anti-tumor activity, and its efficacy is entirely CD8+ T-cell dependent. Functional assays (proliferation, migration, metastasis), Western blotting (β-catenin, PD-L1), in vivo xenograft and allogeneic mouse models, CD8+ T-cell depletion experiments, flow cytometry Journal of experimental & clinical cancer research / Frontiers in immunology Medium 38167452 41573582

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2020 A reference map of the human binary protein interactome. Nature 849 32296183
1992 Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues. Cancer research 843 1596899
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2005 Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors. The American journal of pathology 504 15743802
2006 Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton. Cancer cell 472 16616332
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2004 Lymphatic neoangiogenesis in human kidney transplants is associated with immunologically active lymphocytic infiltrates. Journal of the American Society of Nephrology : JASN 402 14978162
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2007 Involvement of the snake toxin receptor CLEC-2, in podoplanin-mediated platelet activation, by cancer cells. The Journal of biological chemistry 400 17616532
1994 Purification of CpG islands using a methylated DNA binding column. Nature genetics 363 8012384
2006 Podoplanin binds ERM proteins to activate RhoA and promote epithelial-mesenchymal transition. Journal of cell science 312 17046996
2020 Cancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4+ and PDPN+ CAFs to clinical outcome. Nature cancer 260 35122040
2006 The potential role of podoplanin in tumour invasion. British journal of cancer 257 17179989
2005 Characterization of human PA2.26 antigen (T1alpha-2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas. International journal of cancer 241 15515019
2003 Molecular identification of Aggrus/T1alpha as a platelet aggregation-inducing factor expressed in colorectal tumors. The Journal of biological chemistry 239 14522983
2010 Novel function for blood platelets and podoplanin in developmental separation of blood and lymphatic circulation. Blood 230 20110424
2006 E11/gp38 selective expression in osteocytes: regulation by mechanical strain and role in dendrite elongation. Molecular and cellular biology 222 16738320
2003 NKG2D-mediated natural killer cell protection against cytomegalovirus is impaired by viral gp40 modulation of retinoic acid early inducible 1 gene molecules. The Journal of experimental medicine 206 12756263
2006 Increased expression of podoplanin in malignant astrocytic tumors as a novel molecular marker of malignant progression. Acta neuropathologica 201 16596424
2008 Podoplanin expression by cancer associated fibroblasts predicts poor prognosis of lung adenocarcinoma. International journal of cancer 193 18546264
2005 Enhanced expression of Aggrus (T1alpha/podoplanin), a platelet-aggregation-inducing factor in lung squamous cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 190 16006773
2017 Podoplanin expression in primary brain tumors induces platelet aggregation and increases risk of venous thromboembolism. Blood 183 28073783
2007 The platelet aggregation-inducing factor aggrus/podoplanin promotes pulmonary metastasis. The American journal of pathology 167 17392172
2013 Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2. PloS one 165 23991201
1994 Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening. Genomics 163 7829101
2008 Podoplanin: a novel marker for oral cancer risk in patients with oral premalignancy. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 161 18202409
2018 Podoplanin: An emerging cancer biomarker and therapeutic target. Cancer science 159 29575529
2019 Platelets and cancer-associated thrombosis: focusing on the platelet activation receptor CLEC-2 and podoplanin. Blood 154 31778548
2002 MCMV glycoprotein gp40 confers virus resistance to CD8+ T cells and NK cells in vivo. Nature immunology 152 12021778
2006 The DNA sequence and biological annotation of human chromosome 1. Nature 144 16710414
2000 Molecular cloning and expression of a gene encoding Cryptosporidium parvum glycoproteins gp40 and gp15. Infection and immunity 139 10858228
2004 Aggrus: a diagnostic marker that distinguishes seminoma from embryonal carcinoma in testicular germ cell tumors. Oncogene 134 15361850
2013 Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas. Molecular cancer 130 24354864
2012 Platelet activation receptor CLEC-2 regulates blood/lymphatic vessel separation by inhibiting proliferation, migration, and tube formation of lymphatic endothelial cells. The Journal of biological chemistry 130 22556408
2008 Brachyury, SOX-9, and podoplanin, new markers in the skull base chordoma vs chondrosarcoma differential: a tissue microarray-based comparative analysis. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 129 18820665
1999 Identification of PA2.26 antigen as a novel cell-surface mucin-type glycoprotein that induces plasma membrane extensions and increased motility in keratinocytes. Journal of cell science 127 10574709
2010 miR-29b and miR-125a regulate podoplanin and suppress invasion in glioblastoma. Genes, chromosomes & cancer 122 20665731
2015 Podoplanin-expressing cancer-associated fibroblasts lead and enhance the local invasion of cancer cells in lung adenocarcinoma. International journal of cancer 115 25648219
2005 Alteration of tail fiber protein gp38 enables T2 phage to infect Escherichia coli O157:H7. Journal of biotechnology 115 15607229
2006 Podoplanin expression in primary central nervous system germ cell tumors: a useful histological marker for the diagnosis of germinoma. Acta neuropathologica 111 16718353
2006 Conservation of a platelet activating domain of Aggrus/podoplanin as a platelet aggregation-inducing factor. Gene 111 16766141
2008 Podoplanin, a novel marker of tumor-initiating cells in human squamous cell carcinoma A431. Biochemical and biophysical research communications 110 18539139
1988 The B cell-associated CD37 antigen (gp40-52). Structure and subcellular expression of an extensively glycosylated glycoprotein. Journal of immunology (Baltimore, Md. : 1950) 101 3257508
2018 Peripheral PDGFRα+gp38+ mesenchymal cells support the differentiation of fetal liver-derived ILC2. The Journal of experimental medicine 100 29728440
1997 Induction of PA2.26, a cell-surface antigen expressed by active fibroblasts, in mouse epidermal keratinocytes during carcinogenesis. Molecular carcinogenesis 84 9328432
2004 Functional sialylated O-glycan to platelet aggregation on Aggrus (T1alpha/Podoplanin) molecules expressed in Chinese hamster ovary cells. The Journal of biological chemistry 83 15231832
2006 Identity of M2A (D2-40) antigen and gp36 (Aggrus, T1A-2, podoplanin) in human developing testis, testicular carcinoma in situ and germ-cell tumours. Virchows Archiv : an international journal of pathology 81 16736189
1984 Isolation and characterization of a human T lymphocyte-associated glycoprotein (gp40). Journal of immunology (Baltimore, Md. : 1950) 81 6609985
2023 PDPN positive CAFs contribute to HER2 positive breast cancer resistance to trastuzumab by inhibiting antibody-dependent NK cell-mediated cytotoxicity. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 78 36812747
2011 The gp38 adhesins of the T4 superfamily: a complex modular determinant of the phage's host specificity. Genome biology and evolution 77 21746838
2000 The luminal part of the murine cytomegalovirus glycoprotein gp40 catalyzes the retention of MHC class I molecules. The EMBO journal 71 10698929
2023 A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability. Nature communications 64 37898647
1996 Expression of gp40, the murine homologue of human epithelial cell adhesion molecule (Ep-CAM), by murine dendritic cells. European journal of immunology 56 8566052
2008 Tetraspanin family member CD9 inhibits Aggrus/podoplanin-induced platelet aggregation and suppresses pulmonary metastasis. Blood 55 18541721
2013 Serines in the intracellular tail of podoplanin (PDPN) regulate cell motility. The Journal of biological chemistry 52 23530051
2007 Cryptosporidium parvum glycoprotein gp40 localizes to the sporozoite surface by association with gp15. Molecular and biochemical parasitology 52 17719100
2012 The impact of Aggrus/podoplanin on platelet aggregation and tumour metastasis. Journal of biochemistry 50 22992842
1994 Antibody reactivity to the immunodominant epitopes of the caprine arthritis-encephalitis virus gp38 transmembrane protein associates with the development of arthritis. Journal of virology 50 7933096
2012 Functional invadopodia formation through stabilization of the PDPN transcript by IMP-3 and cancer-stromal crosstalk for PDPN expression. Carcinogenesis 49 22859271
2011 Prevention of hematogenous metastasis by neutralizing mice and its chimeric anti-Aggrus/podoplanin antibodies. Cancer science 48 21824222
2021 A CCHFV DNA vaccine protects against heterologous challenge and establishes GP38 as immunorelevant in mice. NPJ vaccines 46 33654101
2006 Proteolytic processing of the Cryptosporidium glycoprotein gp40/15 by human furin and by a parasite-derived furin-like protease activity. Infection and immunity 45 17043102
1996 Local concentration of folate binding protein GP38 in sections of human ovarian carcinoma by in vitro quantitative autoradiography. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 45 8691264
2000 Ectopic expression of PA2.26 antigen in epidermal keratinocytes leads to destabilization of adherens junctions and malignant progression. Laboratory investigation; a journal of technical methods and pathology 44 11092535
1991 Direct involvement of CD7 (gp40) in activation of TcR gamma/delta+ T cells. European journal of immunology 42 1709867
2020 Structure and Characterization of Crimean-Congo Hemorrhagic Fever Virus GP38. Journal of virology 39 31996434
2010 A distinct subset of podoplanin (gp38) expressing F4/80+ macrophages mediate phagocytosis and are induced following zymosan peritonitis. FEBS letters 39 20682314
1997 Molecular characterization of gp40, a mucin-type glycoprotein from the apical plasma membrane of Madin-Darby canine kidney cells (type I). The Biochemical journal 37 9337856
2023 PDPN+ CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX. Cell death & disease 36 37993428
1987 Use of the monoclonal antibody WR17, identifying the CD37 gp40-45 Kd antigen complex, in the diagnosis of B-lymphoid malignancy. The Journal of pathology 36 3305845
2014 Clinicopathological correlations of podoplanin (gp38) expression in rheumatoid synovium and its potential contribution to fibroblast platelet crosstalk. PloS one 35 24932813
2018 Peyer's patch myeloid cells infection by Listeria signals through gp38+ stromal cells and locks intestinal villus invasion. The Journal of experimental medicine 33 30355616
2013 Expression of Aggrus/podoplanin in bladder cancer and its role in pulmonary metastasis. International journal of cancer 33 24222607
2019 Podoplanin (PDPN) affects the invasiveness of thyroid carcinoma cells by inducing ezrin, radixin and moesin (E/R/M) phosphorylation in association with matrix metalloproteinases. BMC cancer 29 30654768
2012 Structural basis of mouse cytomegalovirus m152/gp40 interaction with RAE1γ reveals a paradigm for MHC/MHC interaction in immune evasion. Proceedings of the National Academy of Sciences of the United States of America 27 23169621
2011 Serum IgG response to Cryptosporidium immunodominant antigen gp15 and polymorphic antigen gp40 in children with cryptosporidiosis in South India. Clinical and vaccine immunology : CVI 26 21288997
2010 Direct interaction of the mouse cytomegalovirus m152/gp40 immunoevasin with RAE-1 isoforms. Biochemistry 26 20166740
2015 PKA and CDK5 can phosphorylate specific serines on the intracellular domain of podoplanin (PDPN) to inhibit cell motility. Experimental cell research 24 25959509
2002 C-Terminal gp40 peptide analogs inhibit feline immunodeficiency virus: cell fusion and virus spread. Journal of virology 24 12186891
2008 Regulation of podoplanin/PA2.26 antigen expression in tumour cells. Involvement of calpain-mediated proteolysis. The international journal of biochemistry & cell biology 23 19146981
2007 Stable expression of Cryptosporidium parvum glycoprotein gp40/15 in Toxoplasma gondii. Molecular and biochemical parasitology 20 17275106
2024 PDPN/CCL2/STAT3 feedback loop alter CAF heterogeneity to promote angiogenesis in colorectal cancer. Angiogenesis 19 39115624
2002 Amino acid alterations in Gp38 of host range mutants of PP01 and evidence for their infection of an ompC null mutant of Escherichia coli O157:H7. FEMS microbiology letters 18 12435509
2022 PDPN contributes to constructing immunosuppressive microenvironment in IDH wildtype glioma. Cancer gene therapy 16 36434176
2025 PDPN+ cancer-associated fibroblasts enhance gastric cancer angiogenesis via AKT/NF-κB activation and the CCL2-ACKR1 axis. MedComm 15 39764562
2024 A novel PDPN antagonist peptide CY12-RP2 inhibits melanoma growth via Wnt/β-catenin and modulates the immune cells. Journal of experimental & clinical cancer research : CR 15 38167452
2020 PDPN Is Expressed in Various Types of Canine Tumors and Its Silencing Induces Apoptosis and Cell Cycle Arrest in Canine Malignant Melanoma. Cells 15 32380790
2020 Cryptosporidium parvum gp40/15 Is Associated with the Parasitophorous Vacuole Membrane and Is a Potential Vaccine Target. Microorganisms 14 32143441
2018 Cytomegalovirus gp40/m152 Uses TMED10 as ER Anchor to Retain MHC Class I. Cell reports 14 29874591
1996 Novel mutants in the 5' upstream region of the portal protein gene 20 overcome a gp40-dependent prohead assembly block in bacteriophage T4. Journal of molecular biology 14 8918937
2021 The neutrophil protein CD177 is a novel PDPN receptor that regulates human cancer-associated fibroblast physiology. PloS one 13 34879110
2014 Suppression of Aggrus/podoplanin-induced platelet aggregation and pulmonary metastasis by a single-chain antibody variable region fragment. Cancer medicine 11 25132683
2008 Antiviral activity of membrane fusion inhibitors that target gp40 of the feline immunodeficiency virus envelope protein. Veterinary microbiology 10 19036536
2015 The murine cytomegalovirus immunoevasin gp40 binds MHC class I molecules to retain them in the early secretory pathway. Journal of cell science 9 26527401
2025 Antibodies targeting Crimean-Congo hemorrhagic fever virus GP38 limit vascular leak and viral spread. Science translational medicine 8 39970234
2024 Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38. Cell reports 8 39002130
2017 PDPN gene promotes the proliferation of immature Bovine Sertoli cells in vitro. Animal reproduction science 8 28233584
2016 MicroRNA-203 inhibits tumour growth and metastasis through PDPN. Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery 8 27775879
2007 The role of NKG2D signaling in inhibition of cytotoxic T-lymphocyte lysis by the Murine cytomegalovirus immunoevasin m152/gp40. Journal of virology 8 17855532
2022 PDPN marks a subset of aggressive and radiation-resistant glioblastoma cells. Frontiers in oncology 7 36059614
2022 Uterus globulin associated protein 1 (UGRP1) binds podoplanin (PDPN) to promote a novel inflammation pathway during Streptococcus pneumoniae infection. Clinical and translational medicine 6 35652821
2024 Crimean Congo hemorrhagic fever virus nucleoprotein and GP38 subunit vaccine combination prevents morbidity in mice. NPJ vaccines 5 39143104
2021 The murine cytomegalovirus immunoevasin gp40/m152 inhibits NKG2D receptor RAE-1γ by intracellular retention and cell surface masking. Journal of cell science 5 34085696
1996 Binding characteristics and antitumor properties of 1A10 bispecific antibody recognizing gp40 and human transferrin receptor. Cancer research 5 8548750
2024 Role of Podoplanin (PDPN) in Advancing the Progression and Metastasis of Glioblastoma Multiforme (GBM). Cancers 4 39682237
2022 Serum IgG Responses to gp15 and gp40 Protein-Derived Synthetic Peptides From Cryptosporidium parvum. Frontiers in cellular and infection microbiology 4 35127561
2020 Identification and functional analyses of a cell-death inhibitor encoded by guinea pig cytomegalovirus gp38.1 in cell culture and in animals. The Journal of general virology 4 32915127
2019 Immunolocalization of podoplanin/E11/gp38, CD44, and endomucin in the odontoblastic cell layer of murine tooth germs. Biomedical research (Tokyo, Japan) 4 31413234
2010 A transmembrane glycoprotein, gp38, is a novel marker for immature hepatic progenitor cells in fetal mouse livers. In vitro cellular & developmental biology. Animal 4 21104040
1987 GP38, P28-I and P28-II: candidates for a vaccine against schistosomiasis. Memorias do Instituto Oswaldo Cruz 4 2474122
2024 Inhibiting MMP13 Attenuates Deep Vein Thrombosis in a Mouse Model by Reducing the Expression of Pdpn. Current medical science 3 38619683
1988 Isolation and characterization of the human adenocarcinoma-associated glycoprotein gp40. Biotechnology and applied biochemistry 3 3069116
2025 Knockdown of PDPN in astrocytes reduces hippocampal inflammation in T2DM mice. Frontiers in immunology 2 39911382
2025 Gut-derived Faecalibaculum rodentium exerts anti-cancer effects on colorectal cancer by modulating PDPN-CLEC-2 signaling pathway. mSystems 2 40693815
2024 Crimean-Congo Hemorrhagic Fever Survivors Elicit Protective Non-Neutralizing Antibodies that Target 11 Overlapping Regions on Viral Glycoprotein GP38. bioRxiv : the preprint server for biology 2 38496658
2024 Antibodies targeting Crimean-Congo hemorrhagic fever virus GP38 limit vascular leak and viral spread. bioRxiv : the preprint server for biology 2 38826290
2022 Sorting and Manipulation of Human PGC-LC Using PDPN and Hanging Drop Cultures. Cells 2 36497094
2013 PI3K p110δ is expressed by gp38(-)CD31(+) and gp38(+)CD31(+) spleen stromal cells and regulates their CCL19, CCL21, and LTβR mRNA levels. PloS one 2 24009720
1993 Antibodies specific for gp40 inhibit cell-cell adhesion by cross-linking the protein on the surface of Dictyostelium purpureum. Journal of cellular biochemistry 2 8227191
2025 PDPN+ cancer-associated fibroblasts correlate with the neoadjuvant immunotherapy response in gastric cancer. APL bioengineering 1 40895767
2024 Stable expression of mucin glycoproteins GP40 and GP15 of Cryptosporidium parvum in Toxoplasma gondii. Parasites & vectors 1 38360646
2024 Combining RNAscope, Immunohistochemistry (IHC) and Digital Image Analysis to Assess Podoplanin (PDPN) Protein and PDPN_mRNA Expression on Formalin-Fixed Paraffin-Embedded Normal Human Placenta Tissues. Current issues in molecular biology 1 38920982
2024 PDPN/CLEC-2 axis modulates megakaryocyte subtypes in a hematopoietic stem cell-regulating megakaryocyte-dominant manner. Thrombosis research 1 39615442
2026 Targeting PDPN enhances antitumor T-cell activity by disrupting β-catenin-mediated PD-L1 expression in melanoma. Frontiers in immunology 0 41573582
2026 The gp38 protein inhibits host adsorption of phage vB_EcoM_SD286. Frontiers in microbiology 0 41767561
2025 Immunogenicity of NSDV GP38 and the role of furin in GP38 proteolytic processing. Journal of virology 0 40492757
2025 PDPN+LTBP1+ cancer-associated fibroblasts induce a liver pre-metastatic niche in gastric cancer via PDPN/YAP/LTBP1 and CCL11/CCR3 axis. Cell communication and signaling : CCS 0 41029689