Affinage

PECAM1

Platelet endothelial cell adhesion molecule · UniProt P16284

Length
738 aa
Mass
82.5 kDa
Annotated
2026-04-29
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PECAM1 (CD31) is an immunoglobulin superfamily transmembrane glycoprotein that functions as a homophilic adhesion receptor and mechanotransducer at endothelial cell-cell junctions, integrating cell adhesion, vascular barrier maintenance, leukocyte transendothelial migration, and inhibitory signaling on platelets and immune cells. At endothelial junctions, PECAM1 forms a mechanosensory complex with VE-cadherin, VEGFR2, and PIEZO1; physical traction during leukocyte diapedesis triggers SHP-2 dissociation from PECAM1's ITIM-containing cytoplasmic tail, enabling SHP-2-mediated dephosphorylation of VE-cadherin Y731 and junction opening, a process requiring Ca²⁺ signaling and non-muscle myosin II (PMID:33604918, PMID:37643615, PMID:37005489). PECAM1 maintains endothelial barrier integrity through β-catenin stabilization via GSK-3β modulation and a glycolysis-coupled Akt/FoxO1/cMyc pathway, and transduces H₂O₂-induced activation of a Src-dependent non-selective cation channel (PMID:16816383, PMID:32681081, PMID:11927609). On leukocytes and platelets, PECAM1 cytoplasmic signaling activates Rap1 to upregulate integrin adhesion, recruits SHP-1/SHP-2 phosphatases to inhibit platelet activation and promote dendritic cell tolerogenesis, and undergoes TCR-driven ectodomain shedding that disables its inhibitory function (PMID:10725328, PMID:19850043, PMID:24616502, PMID:20400708).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1990 High

    Molecular cloning revealed PECAM1 as a six-Ig-domain transmembrane glycoprotein of the Ig superfamily concentrated at endothelial junctions, establishing its identity as a potential adhesion molecule.

    Evidence cDNA cloning from endothelial libraries with sequence analysis and immunostaining by two independent groups

    PMID:1690453 PMID:2351935

    Open questions at the time
    • No functional adhesion data yet
    • Ligand/counter-receptor unknown
    • Signaling capacity not addressed
  2. 1992 High

    Reconstitution in null cells demonstrated that PECAM1 localizes to cell-cell contacts, promotes adhesion, and inhibits migration in a cytoplasmic-domain-dependent manner, establishing it as a functional adhesion molecule with signaling requirements.

    Evidence Transfection of full-length vs. extracellular-only constructs into NIH/3T3 cells with migration assays and immunofluorescence

    PMID:1429859

    Open questions at the time
    • Cytoplasmic domain signaling mechanism unresolved
    • Nature of adhesive interaction (homophilic vs. heterophilic) not determined
  3. 1995 High

    Blocking experiments in vitro and in vivo established that PECAM1 homophilic interaction is specifically required for the diapedesis step of leukocyte transendothelial migration, defining its central role in inflammation.

    Evidence Antibody/recombinant protein blocking in transmigration assays and thioglycollate peritonitis model

    PMID:7722409

    Open questions at the time
    • Molecular mechanism linking homophilic engagement to junction opening unknown
    • Endothelial vs. leukocyte PECAM1 relative contributions not genetically dissected
  4. 1995 Medium

    TNF-α/IFN-γ were shown to redistribute junctional PECAM1 without changing surface levels, and antibody blocking in vivo caused vascular leakage, linking PECAM1 junctional localization to barrier function.

    Evidence Flow cytometry, subcellular fractionation, RT-PCR on HUVECs; in vivo antibody injection with permeability readout

    PMID:7589563 PMID:7759892

    Open questions at the time
    • Mechanism of redistribution unclear
    • Whether barrier loss is direct or secondary to junction disassembly not resolved
  5. 1997 High

    A burst of discoveries defined PECAM1's signaling repertoire: engagement triggers sustained Ca²⁺ influx requiring the cytoplasmic domain; tyrosine-phosphorylated PECAM1 recruits SHP-2 phosphatase; and PECAM1 associates with β-catenin, linking it to adherens junction regulation and tube formation.

    Evidence Single-cell fluorometry with domain mutants; co-IP and in vitro phosphatase assays for SHP-2; β-catenin co-IP and collagen gel tube assays with blocking antibodies

    PMID:9120301 PMID:9388260 PMID:9421484

    Open questions at the time
    • Downstream targets of SHP-2 recruited to PECAM1 not identified
    • Nature of the Ca²⁺ channel unknown
    • β-catenin association site on PECAM1 not mapped
  6. 2000 High

    PECAM1 cytoplasmic signaling was shown to selectively activate Rap1 (not Ras) to upregulate integrin function on T cells, and knockout mice revealed that endothelial (not hematopoietic) PECAM1 controls hemostasis.

    Evidence Dominant-negative/activated Rap1 constructs with adhesion assays; PECAM1 KO mice with reciprocal bone marrow transplants and bleeding time

    PMID:10725328 PMID:10880378

    Open questions at the time
    • GEF linking PECAM1 to Rap1 not fully confirmed in endothelial cells
    • Mechanism of endothelial PECAM1 control of hemostasis undefined
  7. 2002 High

    Two distinct functions were delineated: PECAM1 homophilic engagement on viable leukocytes drives active detachment from macrophages (disabled by apoptosis, converting CD31 to a tether for efferocytosis), and H₂O₂-activated PECAM1 opens a Src-dependent non-selective cation channel requiring its cytoplasmic tyrosines.

    Evidence Flow-based macrophage binding assay comparing viable vs. apoptotic cells; patch-clamp electrophysiology in PECAM1-reconstituted REN cells with domain mutants

    PMID:11927609 PMID:12110892

    Open questions at the time
    • Molecular identity of the cation channel not determined
    • Signaling switch between viable detachment and apoptotic tethering not molecularly defined
  8. 2006 High

    Genetic knockout studies showed PECAM1 stabilizes β-catenin at adherens junctions by recruiting SHP-2 to dephosphorylate β-catenin tyrosines and modulating GSK-3β, explaining barrier fragility in PECAM1-null endothelium.

    Evidence PECAM1 KO endothelial cells with phospho-specific Western blotting, co-IP, shear stress and histamine stimulation

    PMID:16816383

    Open questions at the time
    • Direct GSK-3β regulation mechanism by PECAM1 not fully dissected
    • Whether β-catenin stabilization is the sole barrier-maintenance mechanism unclear
  9. 2010 High

    TCR-driven ectodomain shedding of CD31 from T cells was identified as a mechanism that disables CD31 inhibitory signaling by preventing cis-homo-oligomerization; a juxtamembrane peptide could restore ITIM phosphorylation and SHP-2 activation.

    Evidence Flow cytometry, soluble CD31 detection in plasma, T cell activation assays, in vivo peptide rescue in mice

    PMID:20400708

    Open questions at the time
    • Protease responsible for ectodomain shedding not identified
    • Therapeutic applicability of juxtamembrane peptide not established
  10. 2014 High

    CD31 inhibitory signaling was extended to dendritic cells: SHP-1-dependent suppression of NF-κB drives tolerogenic DC function and regulatory T cell induction; separately, NEU1 sialidase-mediated desialylation of CD31 was shown to inhibit angiogenesis.

    Evidence DC maturation assays with NF-κB reporters, adoptive DC transfer in EAE model; lectin blotting, CD31-null epistasis, tube formation assays

    PMID:24550400 PMID:24616502

    Open questions at the time
    • Structural basis for how sialylation state modulates CD31 adhesion/signaling unknown
    • Whether SHP-1 vs. SHP-2 usage in DCs is context-dependent not resolved
  11. 2020 High

    CD31 was identified as the receptor for Clostridium perfringens β-toxin via its Ig6 domain, and its barrier-maintenance function was linked to a glycolytic pathway involving SHP-Akt-FoxO1 nuclear exclusion and β-catenin/cMyc-driven transcription.

    Evidence Ectopic expression in resistant cells and liposomes with domain mapping for CPB; CD31 KO mice with glycolytic flux measurements and pharmacological Akt/AMPK rescue

    PMID:32497498 PMID:32681081

    Open questions at the time
    • How Ig6 domain engagement by CPB leads to membrane damage not structurally resolved
    • Whether glycolytic barrier maintenance operates in all vascular beds unknown
  12. 2021 High

    The diapedesis mechanism was resolved: leukocyte traction on PECAM1 causes SHP-2 to dissociate from PECAM1 and dephosphorylate VE-cadherin Y731, enabling cadherin endocytosis and junction opening, dependent on Ca²⁺ and non-muscle myosin II.

    Evidence SHP-2 binding-site mutants of PECAM1, VE-cadherin Y731 phospho-mutant mice, in vitro and in vivo diapedesis assays

    PMID:33604918

    Open questions at the time
    • How PECAM1 senses mechanical force at the molecular level not resolved
    • Whether SHP-2 acts catalytically on VE-cadherin in cis or after release not fully distinguished
  13. 2023 High

    PECAM1 was placed in a mechanotransduction complex with PIEZO1, VE-cadherin, and VEGFR2: PECAM1 directs PIEZO1 to junctions via its N-terminal extracellular domain, and leukocyte traction activates VEGFR2 Y1175 phosphorylation independently of VEGF or VEGFR2 kinase activity, required for neutrophil extravasation.

    Evidence Endogenous PIEZO1 tagging in mice with co-localization and reconstitution; FLIM force-sensing, endothelial-specific VEGFR2 KO mice, three inflammation models

    PMID:37005489 PMID:37643615

    Open questions at the time
    • How VEGFR2 Y1175 is phosphorylated without its own kinase activity is unclear—trans-phosphorylation source not identified
    • Stoichiometry and structure of the PECAM1-PIEZO1-VEGFR2-VE-cadherin complex unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of force sensing by PECAM1 and the full stoichiometry of its mechanosensory complex remain undefined, as does the molecular identity of the PECAM1-dependent cation channel.
  • No high-resolution structure of PECAM1 in complex with junctional partners
  • Molecular identity of H₂O₂-activated cation channel downstream of PECAM1 unknown
  • Protease(s) mediating CD31 ectodomain shedding on T cells not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0098772 molecular function regulator activity 5 GO:0098631 cell adhesion mediator activity 4
Localization
GO:0005886 plasma membrane 5 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-168256 Immune System 6 R-HSA-1500931 Cell-Cell communication 4 R-HSA-109582 Hemostasis 3
Partners
CDH5CTNNB1KDRPIEZO1PTPN11PTPN6RAP1A
Complex memberships
PECAM1-PIEZO1 junctional complexPECAM1-VE-cadherin-VEGFR2 mechanosensory complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 PECAM-1 (CD31) was cloned and identified as a 130 kDa integral membrane glycoprotein with six extracellular immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail; it is a member of the CAM subgroup of the Ig superfamily expressed on platelets, leukocytes, and enriched at endothelial cell intercellular junctions, consistent with a role in cellular recognition and adhesion. cDNA cloning from endothelial cell library, sequence analysis, immunostaining Science High 1690453
1990 CD31 is a member of the Ig superfamily most closely related to carcinoembryonic antigen, comprising four contiguous C2 domains, and is concentrated at cell-cell contacts in endothelial cells, consistent with function as an intercellular adhesion molecule. cDNA cloning by transient expression, sequence analysis, immunofluorescence localization The Journal of experimental medicine High 2351935
1992 Full-length PECAM-1 transfected into NIH/3T3 null cells localizes to sites of cell-cell contact at the cell periphery, promotes cell-cell adhesion, and decreases the rate of cell migration, demonstrating that the intact molecule (requiring its cytoplasmic domain) is necessary for junction localization and migration inhibition. Transfection of full-length vs. extracellular-domain-only constructs into NIH/3T3 cells, quantitative migration assays, immunofluorescence Journal of cellular physiology High 1429859
1994 PECAM-1 becomes highly phosphorylated upon cellular activation and, coincident with phosphorylation, associates with the cytoskeleton of activated platelets; engagement of PECAM-1 upregulates integrin function on leukocytes, implicating it as a trigger for leukocyte trafficking. Biochemical fractionation, phosphorylation assays, functional leukocyte adhesion assays Annals of the New York Academy of Sciences Medium 8017765
1995 PECAM-1 mediates a specific homophilic interaction required for the transendothelial migration (diapedesis) phase of neutrophil and monocyte emigration; anti-PECAM-1 antibodies or soluble recombinant PECAM-1 directed against either leukocyte or endothelial PECAM-1 blocked passage across endothelial monolayers by 70–90% without affecting apical adhesion, and a monoclonal antibody against mouse PECAM-1 blocked leukocyte emigration into the peritoneum in vivo. Quantitative in vitro transendothelial migration assay with antibody/recombinant protein blocking, in vivo thioglycollate peritonitis model Journal of leukocyte biology High 7722409
1995 TNF-α and IFN-γ induce redistribution of PECAM-1 away from endothelial cell intercellular junctions without altering total surface expression or transcription; this redistribution is associated with changes in PECAM-1 cytoskeletal association, providing a mechanism by which inflammatory cytokines regulate leukocyte transmigration. Flow cytometry, immunofluorescence, subcellular fractionation, RT-PCR, cytoskeletal association assays on HUVECs Journal of immunology Medium 7759892
1995 PECAM-1 contributes to vascular barrier function; antibody blocking of murine vascular PECAM-1 in vivo caused detectable leakage from hepatic and renal blood vessels, and monolayer permeability assays on native or PECAM-1-transfected cells confirmed a barrier role. Macromolecule permeability assays on endothelial monolayers, in vivo antibody injection with vascular leakage readout FEBS letters Medium 7589563
1997 PECAM-1 engagement induces a slow but sustained increase in intracellular Ca²⁺ in endothelial cells and PECAM-1-transfected cell lines, requiring the cytoplasmic domain, extracellular Ca²⁺, and tyrosine phosphorylation but not receptor cross-linking; this Ca²⁺ signal is accompanied by prostacyclin release. Single-cell fluorometry with anti-PECAM-1 antibodies and Fab fragments, prostacyclin ELISA, cytoplasmic-domain deletion constructs The Journal of clinical investigation High 9421484
1997 PECAM-1 is required for endothelial tube formation in vitro; anti-CD31 antibodies caused endothelial cells to become rounded or form attenuated tube-like structures with large single vacuoles rather than normal tubes, distinct from the VE-cadherin antibody phenotype, and CD31 associates with β-catenin via immunoprecipitation, linking it to the actin cytoskeleton. 3D collagen gel tube formation assay with blocking antibodies, immunoprecipitation for β-catenin association Journal of immunology High 9120301
1997 SHP-2, but not SHP-1, associates with tyrosine-phosphorylated PECAM-1 via its SH2 domains; this association correlates with the extent of PECAM-1 tyrosine phosphorylation, and immune precipitate phosphatase assays show SHP-2 dephosphorylates PECAM-1, identifying a signaling pathway downstream of integrin and immune receptor activation. Co-immunoprecipitation, SH2-domain fusion protein pull-down, in vitro phosphatase assay The Journal of biological chemistry High 9388260
1997 Plasmodium falciparum-infected erythrocytes bind directly to PECAM-1/CD31 on the vascular endothelium; binding occurs to PECAM-1-transfected cells and to recombinant PECAM-1 absorbed onto plastic, is blocked by soluble PECAM-1 or antibodies to domains 1–4, and is augmented by IFN-γ. Binding assays to PECAM-1 transfected cells and recombinant PECAM-1, blocking with soluble PECAM-1 and monoclonal antibodies Nature medicine High 9396614
1999 CD31 exists as a dimer both in solution and on cell membranes (confirmed by ultracentrifugation and chemical cross-linking) and is heavily N-glycosylated (~21% carbohydrate content with 19 neutral and 13 sialylated glycans), suggesting dimerization plays a role in CD31 adhesion and signaling. Analytical ultracentrifugation, chemical cross-linking, mass spectrometry glycan analysis Biochemical and biophysical research communications High 10425179
2000 The cytoplasmic tail of CD31 activates the small GTPase Rap1 (selectively, not Ras, R-Ras, or Rap2) to promote T cell adhesion via β1 (VLA-4) and β2 (LFA-1) integrins; dominant-negative Rap1 or its GAP blocked CD31-dependent adhesion, while activated Rap1 or C3G exchange factor stimulated adhesion. Transfection of cytoplasmic-tail deletion constructs, dominant-negative and activated Rap1 mutants, adhesion assays to ICAM and VCAM The Journal of cell biology High 10725328
2000 PECAM-1 expressed on endothelial cells (but not hematopoietic cells) modulates in vivo bleeding time; PECAM-1-deficient mice showed prolonged bleeding times that were not corrected by wild-type hematopoietic engraftment but were present when PECAM-1-deficient marrow was transplanted into wild-type mice. PECAM-1 knockout mice, bone marrow transplantation experiments, tail bleeding time assay The American journal of pathology High 10880378
2002 CD31-mediated homophilic ligation on viable leukocytes promotes their active, temperature-dependent detachment from macrophages under low shear; apoptosis disables this CD31 detachment signaling, converting CD31 into a tethering molecule that promotes macrophage engulfment of dying cells. Flow-based binding assay of viable vs. apoptotic leukocytes with macrophages, temperature dependence, antibody blocking Nature High 12110892
2002 PECAM-1 transduces endothelial cell responses to H₂O₂ by activating a calcium-permeant non-selective cation current; this requires the PECAM-1 cytoplasmic tyrosine-containing domain and Src family kinase activity, as shown by tyrosine-domain mutants and dialysis of anti-cytoplasmic-domain antibodies. Patch-clamp electrophysiology, Ca²⁺ imaging, stable transfection of PECAM-1 and cytoplasmic-domain mutants into PECAM-1-negative REN cells The Journal of cell biology High 11927609
2003 Clustering of PECAM-1 on endothelial cells triggers a novel endocytic pathway that is distinct from clathrin- and caveolae-mediated endocytosis; internalization requires multimeric conjugates, is inhibited by amiloride and PKC inhibitors (macropinocytosis inhibitors), and depends on actin rearrangements requiring Src kinase and Rho kinase (ROCK). Internalization assays with anti-PECAM-1 conjugates, inhibitor studies, dominant-negative dynamin-2 transfection, actin cytoskeleton imaging Journal of cell science High 12640043
2006 PECAM-1 regulates β-catenin stability at endothelial adherens junctions by modulating GSK-3β activity: PECAM-1 tyrosine phosphorylation upon stimulation recruits SHP-2 and tyrosine-phosphorylated β-catenin, enabling β-catenin dephosphorylation and junction re-annealing; in PECAM-1-null ECs, β-catenin remains tyrosine-phosphorylated, GSK-3β serine phosphorylation (inactivation) is blunted, and β-catenin undergoes increased serine phosphorylation and proteasomal degradation. PECAM-1 knockout endothelial cells, co-immunoprecipitation, phospho-specific Western blotting, shear stress and histamine stimulation assays The American journal of pathology High 16816383
2006 The Kaposi sarcoma herpesvirus ubiquitin ligase K5 ubiquitinates pre-existing CD31 at the cell surface, triggering its endocytosis and lysosomal degradation, while newly synthesized CD31 is degraded by proteasomes in the ER via a mechanism requiring PACS-2 binding to acidic residues in the K5 cytoplasmic tail. Ubiquitination assays, endocytosis/degradation experiments with lysosomal and proteasomal inhibitors, PACS-2 binding mutants, cell migration assays Blood High 16601245
2010 TCR stimulation drives ectodomain cleavage and shedding of CD31 from human T cells, releasing a soluble truncated form detectable in plasma; shedding abolishes CD31 inhibitory function because cis-homo-oligomerization (triggered by trans-homophilic engagement of domain 1) cannot occur on CD31-shed cells; a juxtamembrane peptide (aa 551–574) can restore ITIM phosphorylation and SHP-2 activation on CD31-shed cells. Flow cytometry, Western blot detection of soluble CD31 in plasma, T cell activation assays, phosphorylation assays, in vivo peptide administration in mice Journal of immunology High 20400708
2014 NEU1 sialidase desialylates CD31 (specifically its α2,6-linked sialic acids) when recruited to CD31 in postconfluent endothelial cells; NEU1-mediated desialylation of CD31 inhibits in vitro capillary tube formation, and prior CD31 silencing or use of CD31-null endothelial cells abrogates NEU1's inhibitory effect, placing CD31 sialylation downstream of NEU1 in the angiogenic pathway. Lectin blotting, siRNA knockdown of NEU1 and CD31, adenoviral overexpression of catalytically active vs. dead NEU1, tube formation assays on Matrigel, CD31-null endothelial cells The Journal of biological chemistry High 24550400
2014 CD31 signaling via SHP-1 phosphatase in dendritic cells reduces NF-κB nuclear translocation, expression of costimulatory molecules, and production of IL-12 and IL-6, while increasing TGF-β and IL-10, driving DCs toward tolerogenic function and T-cell tolerance; CD31-conditioned DCs promoted regulatory T cells and suppressed experimental autoimmune encephalomyelitis in vivo. DC maturation assays with CD31 gain/loss of function, NF-κB reporter assay, cytokine ELISA, adoptive transfer of CD31-conditioned antigen-loaded DCs into EAE model Proceedings of the National Academy of Sciences High 24616502
2015 PECAM1 specifically mediates flow-induced (but not HGF-induced) Gab1 tyrosine phosphorylation, membrane translocation of Gab1, and downstream Akt and eNOS activation in endothelial cells; PECAM1 siRNA abolished these flow responses, and PECAM1 knockout mice showed reduced flow-mediated Gab1 and eNOS phosphorylation in vivo. siRNA knockdown, PECAM1 knockout mice, phospho-Western blotting, flow stimulation apparatus, in vivo voluntary wheel running Cellular signalling High 26706435
2020 CD31 is identified as the specific endothelial cell receptor for Clostridium perfringens β-toxin; CD31 expression correlates with cell-type susceptibility, ectopic CD31 expression renders resistant cells and liposomes susceptible to CPB-induced membrane damage, and the extracellular Ig6 domain is essential for the interaction with CPB. Ectopic expression of CD31 in resistant cell lines, liposome reconstitution, domain deletion mapping of Ig6, in vivo mouse experiments Cell host & microbe High 32497498
2020 CD31 receptor-induced signaling preserves endothelial barrier function by triggering a glycolytic response via src-homology phosphatase activation leading to Akt-mediated nuclear exclusion of FoxO1 and β-catenin nuclear translocation, driving cMyc transcription; CD31-deficient mice show pathological microvascular leakage correctable by pharmacological Akt or AMPK activation. CD31-deficient mice, glycolytic flux measurements, pharmacological Akt/AMPK activation, transendothelial resistance assays, signaling pathway analysis Nature communications High 32681081
2021 Leukocyte-induced stimulation of endothelial PECAM-1 causes dissociation of SHP2 phosphatase from PECAM-1, which then directly dephosphorylates VE-cadherin-Y731, enabling VE-cadherin endocytosis and junction opening for diapedesis; this mechanism requires Ca²⁺ signaling, non-muscle myosin II activation, and endothelial cell tension generated by leukocyte docking force on the VE-cadherin-catenin complex. SHP2 binding-site mutants of PECAM-1, VE-cadherin Y731 phospho-mutant mice, in vitro and in vivo leukocyte diapedesis assays, pharmacological inhibitors of myosin II and Ca²⁺ signaling, microscopy The EMBO journal High 33604918
2023 PECAM1 physically interacts with the mechanosensitive PIEZO1 channel at endothelial cell-cell junctions; PECAM1 extracellular N-terminus is critical for this interaction and directs PIEZO1 to junctions; PIEZO1 is required for Ca²⁺-dependent formation of adherens junctions and associated cytoskeleton, supporting a cooperative role in force-dependent junctional remodeling. Endogenous tagging of PIEZO1 in mice, reconstitution studies, high-resolution microscopy (co-localization), shear stress experiments, CDH5 and VEGFR2 interaction comparisons Communications biology High 37005489
2023 Physical traction on endothelial PECAM-1 during leukocyte transendothelial migration (TEM) initiates the endothelial signaling pathway; endothelial PECAM-1 acts as part of a mechanotransduction complex with VE-cadherin and VEGFR2; TEM requires VEGFR2 Y1175 phosphorylation but not VEGF or VEGFR2 kinase activity; endothelial-specific VEGFR2-deficient mice show ≥75% reduction in neutrophil extravasation. Fluorescence lifetime imaging microscopy (FLIM) for force sensing, inducible endothelial-specific VEGFR2-knockout mice, VEGFR2 phospho-mutants, three mouse inflammation models Immunity High 37643615
2009 PECAM-1 expression negatively regulates multiple platelet signaling pathways; PECAM-1 clustering inhibits platelet responses to CRP-XL (collagen receptor pathway), ADP, and thrombin, resulting in a marked combined reduction in thrombus formation. Flow cytometry correlation of PECAM-1 surface expression with platelet reactivity, PECAM-1 clustering assays, thrombus formation assays FEBS letters Medium 19850043
2007 PECAM-1 modulates thrombin-induced tissue factor (TF) expression in endothelial cells via a signaling pathway involving PAR-1, Gαi/o, Rho kinase, p38 MAPK, and Egr-1 nuclear translocation; PECAM-1 promotes PI3K-Akt activation that inversely regulates p38 MAPK and thereby suppresses TF expression; PECAM-1-null mice show increased TF expression and fibrin deposition after renal ischemia-reperfusion. Antisense knockdown of PECAM-1 in HUVECs, PECAM-1 KO mice, pharmacological inhibitors (PAR-1 antagonist, pertussis toxin, Rho kinase, p38 inhibitor, PI3K inhibitor), TF mRNA and protein assays Journal of cellular physiology High 17111362

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science (New York, N.Y.) 878 1690453
1997 Involvement of endothelial PECAM-1/CD31 in angiogenesis. The American journal of pathology 468 9284815
2007 PECAM-1: a multi-functional molecule in inflammation and vascular biology. Arteriosclerosis, thrombosis, and vascular biology 451 17872453
2016 Endothelial functions of platelet/endothelial cell adhesion molecule-1 (CD31). Current opinion in hematology 448 27055047
2005 CD31- but Not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation. Circulation research 361 15947249
2000 The small GTPase, Rap1, mediates CD31-induced integrin adhesion. The Journal of cell biology 353 10725328
2002 Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment. Nature 280 12110892
1994 Molecular and functional aspects of PECAM-1/CD31. Immunology today 280 7945775
2003 A novel endocytic pathway induced by clustering endothelial ICAM-1 or PECAM-1. Journal of cell science 254 12640043
1999 Functional roles for PECAM-1 (CD31) and VE-cadherin (CD144) in tube assembly and lumen formation in three-dimensional collagen gels. The American journal of pathology 196 10487846
1997 PECAM-1/CD31, an endothelial receptor for binding Plasmodium falciparum-infected erythrocytes. Nature medicine 169 9396614
1990 Molecular cloning of CD31, a putative intercellular adhesion molecule closely related to carcinoembryonic antigen. The Journal of experimental medicine 166 2351935
1997 Endothelial cell tube formation depends on cadherin 5 and CD31 interactions with filamentous actin. Journal of immunology (Baltimore, Md. : 1950) 162 9120301
1995 The role of PECAM-1 (CD31) in leukocyte emigration: studies in vitro and in vivo. Journal of leukocyte biology 162 7722409
1995 IFN-gamma and TNF-alpha induce redistribution of PECAM-1 (CD31) on human endothelial cells. Journal of immunology (Baltimore, Md. : 1950) 144 7759892
2007 Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children. European journal of immunology 140 17935071
1994 The role of PECAM-1 in vascular cell biology. Annals of the New York Academy of Sciences 126 8017765
2009 Circulating monocytes expressing CD31: implications for acute and chronic angiogenesis. The American journal of pathology 123 19349357
2018 Lung Repair and Regeneration in ARDS: Role of PECAM1 and Wnt Signaling. Chest 114 30392791
1992 Platelet endothelial cell adhesion molecule, PECAM-1, modulates cell migration. Journal of cellular physiology 113 1429859
2013 An immunologist's guide to CD31 function in T-cells. Journal of cell science 109 23761922
2010 Both CD31(+) and CD31⁻ naive CD4(+) T cells are persistent HIV type 1-infected reservoirs in individuals receiving antiretroviral therapy. The Journal of infectious diseases 97 20979453
2020 CD31 as a Therapeutic Target in Atherosclerosis. Circulation research 93 32324506
2000 PECAM-1 (CD31) expression modulates bleeding time in vivo. The American journal of pathology 91 10880378
2009 Glatiramer acetate improves regulatory T-cell function by expansion of naive CD4(+)CD25(+)FOXP3(+)CD31(+) T-cells in patients with multiple sclerosis. Journal of neuroimmunology 90 19646767
1998 Transmigration of CD34+ cells across specialized and nonspecialized endothelium requires prior activation by growth factors and is mediated by PECAM-1 (CD31). Blood 90 9454749
1997 The protein-tyrosine phosphatase SHP-2 associates with tyrosine-phosphorylated adhesion molecule PECAM-1 (CD31). The Journal of biological chemistry 89 9388260
2000 Irradiation induced expression of CD31, ICAM-1 and VCAM-1 in human microvascular endothelial cells. Anticancer research 84 11131637
2006 Kaposi sarcoma herpesvirus K5 removes CD31/PECAM from endothelial cells. Blood 78 16601245
2015 PECAM-1 isoforms, eNOS and endoglin axis in regulation of angiogenesis. Clinical science (London, England : 1979) 76 25976664
1995 The platelet endothelial cell adhesion molecule-1 (PECAM1) contributes to endothelial barrier function. FEBS letters 75 7589563
2023 PIEZO1 and PECAM1 interact at cell-cell junctions and partner in endothelial force sensing. Communications biology 73 37005489
2009 CD38/CD31 interactions activate genetic pathways leading to proliferation and migration in chronic lymphocytic leukemia cells. Molecular medicine (Cambridge, Mass.) 73 19956559
1999 Thrombospondin-1, PECAM-1, and regulation of angiogenesis. Histology and histopathology 73 9987673
1998 Engagement of human PECAM-1 (CD31) on human endothelial cells increases intracellular calcium ion concentration and stimulates prostacyclin release. The Journal of clinical investigation 73 9421484
2019 Mechanotransduction, immunoregulation, and metabolic functions of CD31 in cardiovascular pathophysiology. Cardiovascular research 70 31119265
1991 Biochemical characterization of PECAM-1 (CD31 antigen) on human platelets. Thrombosis and haemostasis 70 1796415
2006 PECAM-1 affects GSK-3beta-mediated beta-catenin phosphorylation and degradation. The American journal of pathology 65 16816383
2010 TCR stimulation drives cleavage and shedding of the ITIM receptor CD31. Journal of immunology (Baltimore, Md. : 1950) 60 20400708
2014 NEU1 sialidase regulates the sialylation state of CD31 and disrupts CD31-driven capillary-like tube formation in human lung microvascular endothelia. The Journal of biological chemistry 59 24550400
2014 Vascular channels formed by subpopulations of PECAM1+ melanoma cells. Nature communications 59 25335460
1995 Immunostaining for CD31 and CD34 in Kaposi sarcoma. Journal of clinical pathology 58 8543622
1993 Platelet endothelial cell adhesion molecule (CD31). Current topics in microbiology and immunology 58 8313722
1998 CD31 immunoreactivity in carcinomas and mesotheliomas. American journal of clinical pathology 56 9728613
2020 Preservation of microvascular barrier function requires CD31 receptor-induced metabolic reprogramming. Nature communications 54 32681081
2010 VEGF and CD31 association in pituitary adenomas. Endocrine pathology 53 20473646
2016 Endothelial PECAM-1 and its function in vascular physiology and atherogenic pathology. Experimental and molecular pathology 51 27079772
2014 Cultured human bone marrow-derived CD31(+) cells are effective for cardiac and vascular repair through enhanced angiogenic, adhesion, and anti-inflammatory effects. Journal of the American College of Cardiology 50 25323256
2023 Mesenchymal Stem Cell Aggregation-Released Extracellular Vesicles Induce CD31+ EMCN+ Vessels in Skin Regeneration and Improve Diabetic Wound Healing. Advanced healthcare materials 49 36999744
2011 Mesangial cell integrin αvβ8 provides glomerular endothelial cell cytoprotection by sequestering TGF-β and regulating PECAM-1. The American journal of pathology 48 21281793
1999 Irradiation induces upregulation of CD31 in human endothelial cells. Arteriosclerosis, thrombosis, and vascular biology 48 10073961
1999 CD31 (PECAM-1) exists as a dimer and is heavily N-glycosylated. Biochemical and biophysical research communications 47 10425179
2014 CD31 is a key coinhibitory receptor in the development of immunogenic dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 46 24616502
2021 Coronary stent CD31-mimetic coating favours endothelialization and reduces local inflammation and neointimal development in vivo. European heart journal 45 33580685
2020 Ophiopogonin D promotes bone regeneration by stimulating CD31hi EMCNhi vessel formation. Cell proliferation 45 32080957
2007 CD31 and CD34 expression as immunohistochemical markers of endothelial transdifferentiation in human cutaneous melanoma. Cellular oncology : the official journal of the International Society for Cellular Oncology 45 17429142
2004 Tumor neoangiogenesis by CD31 and CD105 expression evaluation in breast carcinoma tissue microarrays. Clinical cancer research : an official journal of the American Association for Cancer Research 44 15355911
1996 The human PECAM1 gene maps to 17q23. Genomics 44 8661055
2021 PECAM-1 supports leukocyte diapedesis by tension-dependent dephosphorylation of VE-cadherin. The EMBO journal 42 33604918
2020 CD31 (PECAM-1) Serves as the Endothelial Cell-Specific Receptor of Clostridium perfringens β-Toxin. Cell host & microbe 41 32497498
2017 CD31 Expression Determines Redox Status and Chemoresistance in Human Angiosarcomas. Clinical cancer research : an official journal of the American Association for Cancer Research 40 29084920
2016 Roles of PECAM-1 in cell function and disease progression. European review for medical and pharmacological sciences 40 27775789
1999 Expression of PECAM-1/CD31 isoforms in human brain gliomas. Journal of neuro-oncology 40 10448867
2015 The vascular marker CD31 also highlights histiocytes and histiocyte-like cells within cutaneous tumors. American journal of clinical pathology 39 25596243
2010 Physical exercise induces expression of CD31 and facilitates neural function recovery in rats with focal cerebral infarction. Neurological research 39 20483007
1996 PECAM-1 (CD31) expression in the central nervous system and its role in experimental allergic encephalomyelitis in the rat. Journal of neuroscience research 39 8892086
2002 PECAM-1 (CD31) regulates a hydrogen peroxide-activated nonselective cation channel in endothelial cells. The Journal of cell biology 38 11927609
2023 Mechanotransduction via endothelial adhesion molecule CD31 initiates transmigration and reveals a role for VEGFR2 in diapedesis. Immunity 36 37643615
2018 Double immunofluorescence labeling for CD31 and CD105 as a marker for polyether polyurethane-induced angiogenesis in mice. Histology and histopathology 36 30207375
2012 A CD31-derived peptide prevents angiotensin II-induced atherosclerosis progression and aneurysm formation. Cardiovascular research 36 22293851
2007 Atheroprotective effect of CD31 receptor globulin through enrichment of circulating regulatory T-cells. Journal of the American College of Cardiology 36 17659202
2001 Expression of CD31 by cells of extensive ductal in situ and invasive carcinomas of the breast. The Journal of pathology 35 11400156
1997 CD31 (JC70) expression in plasma cells: an immunohistochemical analysis of reactive and neoplastic plasma cells. Journal of clinical pathology 35 9378815
2013 Plasmodium falciparum expressing domain cassette 5 type PfEMP1 (DC5-PfEMP1) bind PECAM1. PloS one 34 23874884
2009 CD31+ T cells represent a functionally distinct vascular T cell phenotype. Blood cells, molecules & diseases 33 19897387
2001 Inhibition of antigen-specific T cell trafficking into the central nervous system via blocking PECAM1/CD31 molecule. Journal of neuropathology and experimental neurology 33 11487054
1999 Human myeloma cells express the CD38 ligand CD31. British journal of haematology 33 10233418
2009 PECAM-1 expression and activity negatively regulate multiple platelet signaling pathways. FEBS letters 31 19850043
1995 Involvement of CD31 in lymphocyte-mediated immune responses: importance of the membrane-proximal immunoglobulin domain and identification of an inhibiting CD31 peptide. Blood 31 7858258
2007 Evaluation of CD31 (PECAM-1) expression using tissue microarray in patients with renal cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 30 17510564
2001 Human CD38 and its ligand CD31 define a unique lamina propria T lymphocyte signaling pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 11259373
2007 The role of platelet/endothelial cell adhesion molecule 1 (CD31) and CD38 antigens in marrow microenvironmental retention of acute myelogenous leukemia cells. Cancer research 29 17875702
2021 Role of aneuploid circulating tumor cells and CD31+ circulating tumor endothelial cells in predicting and monitoring anti-angiogenic therapy efficacy in advanced NSCLC. Molecular oncology 28 34455700
2016 Platelets modulate endothelial cell response to dynamic shear stress through PECAM-1. Thrombosis research 28 28013181
2013 Proangiogenic TIE2(+)/CD31 (+) macrophages are the predominant population of tumor-associated macrophages infiltrating metastatic lymph nodes. Molecules and cells 28 24158612
2015 Endothelial LSP1 Modulates Extravascular Neutrophil Chemotaxis by Regulating Nonhematopoietic Vascular PECAM-1 Expression. Journal of immunology (Baltimore, Md. : 1950) 27 26238489
2007 PECAM-1 modulates thrombin-induced tissue factor expression on endothelial cells. Journal of cellular physiology 27 17111362
2011 CD31 is required on CD4+ T cells to promote T cell survival during Salmonella infection. Journal of immunology (Baltimore, Md. : 1950) 25 21734076
2004 PECAM-1 (CD31) is required for interactions of platelets with endothelial cells after irradiation. Journal of thrombosis and haemostasis : JTH 25 15550034
2020 Low shear stress induces endothelial cell apoptosis and monocyte adhesion by upregulating PECAM‑1 expression. Molecular medicine reports 24 32323830
2014 Altered CD31 expression and activity in helper T cells of acute coronary syndrome patients. Basic research in cardiology 24 25344833
2022 Co-expression of ERG and CD31 in a subset of CIC-rearranged sarcoma: a potential diagnostic pitfall. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 23 35440765
2021 Nestin+/CD31+ cells in the hypoxic perivascular niche regulate glioblastoma chemoresistance by upregulating JAG1 and DLL4. Neuro-oncology 22 33249476
2015 PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation and signaling. Cellular signalling 22 26706435
2022 Comprehensive Immune Profiling Reveals CD56+ Monocytes and CD31+ Endothelial Cells Are Increased in Severe COVID-19 Disease. Journal of immunology (Baltimore, Md. : 1950) 21 34987111
2013 Increased expression of VEGF and CD31 in postradiation rectal tissue: implications for radiation proctitis. Mediators of inflammation 21 23737650
2015 Platelet endothelial cell adhesion molecule-1 (PECAM1) plays a critical role in the maintenance of human vascular endothelial barrier function. Cell biochemistry and function 20 26607202
1999 Vascular-endothelial cadherin (CD144)- but not PECAM-1 (CD31)-based cell-to-cell contacts convey the maintenance of a quiescent endothelial monolayer. International archives of allergy and immunology 20 10592470
2018 Frontline Science: PECAM-1 (CD31) expression in naïve and memory, but not acutely activated, CD8+ T cells. Journal of leukocyte biology 19 30063264
2003 Modulation of PECAM-1 expression and alternative splicing during differentiation and activation of hematopoietic cells. Journal of cellular biochemistry 19 12616538