Affinage

F11R

Junctional adhesion molecule A · UniProt Q9Y624

Length
299 aa
Mass
32.6 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

F11R/JAM-A is an immunoglobulin-superfamily transmembrane adhesion receptor of endothelial and epithelial junctions, platelets, and leukocytes that converts adhesive engagement into intracellular signaling to control leukocyte trafficking, junctional barrier function, epithelial polarity, and cell proliferation (PMID:11812992, PMID:18039951, PMID:23885123). Through its extracellular Ig domains it engages two adhesive modes: a homophilic trans-interaction stabilized by the second Ig domain and a stronger heterophilic interaction with the β2 integrin LFA-1, whose binding to domain 2 cancels homophilic stabilization and drives leukocyte adhesion and transendothelial migration (PMID:11812992, PMID:18849408); trans-dimerization requires residues 43NNP45 and activates Rap2 signaling (PMID:24672055). In inflamed endothelium JAM-A is transcriptionally induced via NF-κB and JAK/STAT and inserted on the luminal surface to support platelet adhesion, and acts sequentially with ICAM-2 and PECAM-1 to mediate stimulus-specific leukocyte transmigration (PMID:21703019, PMID:19211506, PMID:17505016). At junctions JAM-A nucleates a ZO-2/afadin/PDZ-GEF1 complex that activates Rap2c and tunes RhoA-dependent actomyosin contraction to restrict paracellular permeability (PMID:23885123), and drives a C/EBP-α-dependent transcriptional program that upregulates claudin-5 to tighten endothelial barriers (PMID:32673519). Barrier control is gated by phosphorylation: aPKC phosphorylates Ser285 to promote junction maturation and single-lumen specification (reversed by PP2A) (PMID:22371556), while Yes-1-mediated Y280 phosphorylation, opposed by PTPN13, uncouples JAM-A from active Rap2 and disrupts the barrier during cytokine exposure (PMID:30625033). JAM-A also functions as a mechanosensor, with tension activating RhoA through GEF-H1 and p115 RhoGEF in a Ser284-dependent manner, and its loss redistributing tension to a p114RhoGEF/ZO-1 axis (PMID:26985018, PMID:32697990). In epithelia it restrains proliferation in a dimerization-dependent manner by inhibiting Akt/β-catenin signaling and by engaging the Hippo pathway through NF2 and LATS1 to suppress YAP activity (PMID:21372850, PMID:35602956), and it orients the mitotic spindle by triggering Cdc42/PI(3)K signaling to localize cortical dynactin (PMID:26306570). In platelets JAM-A acts as an endogenous inhibitor of integrin αIIbβ3 outside-in signaling (PMID:22271446), and at cell contacts it assembles with tetraspanins CD9/CD81 and αvβ5 integrin, binding Csk to suppress Src and enforce contact inhibition of locomotion (PMID:35293964). JAM-A additionally serves as a strain-specific rotavirus coreceptor whose use is determined by viral VP4 (PMID:25481868).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 High

    Established JAM-A as an adhesive receptor with defined ligands, resolving how a junctional Ig-superfamily protein mediates both leukocyte trafficking and platelet adhesion.

    Evidence JAM-1 transfection with LFA-1-dependent adhesion/transmigration assays and domain deletion; platelet adhesion to inflamed endothelium blocked by soluble F11R and domain peptides

    PMID:11812992 PMID:12008956 PMID:12428104

    Open questions at the time
    • Atomic-resolution structure of the LFA-1 binding interface not defined here
    • Relative in vivo contribution of homophilic vs heterophilic engagement unresolved
  2. 2003 High

    Showed JAM-A engages integrin partners and signals via its cytoplasmic domain, linking adhesion to MAP kinase and angiogenic responses.

    Evidence Co-IP of JAM-1/αvβ3, cytoplasmic domain mutagenesis, and endothelial tube formation assays

    PMID:12750158

    Open questions at the time
    • Direct vs indirect nature of αvβ3 association not defined
    • Cytoplasmic effectors linking JAM-A to MAPK not identified in this study
  3. 2007 High

    Defined the in vivo physiological roles of JAM-A in leukocyte transmigration and intestinal barrier function using genetic loss-of-function.

    Evidence Intravital microscopy and barrier assays in JAM-A knockout mice plus antibody blockade and siRNA, with PECAM-1 epistasis and claudin expression analysis

    PMID:17505016 PMID:18039951

    Open questions at the time
    • Mechanism coupling endothelial JAM-A to transmigration step not molecularly resolved
    • How JAM-A loss raises claudin-10/-15 expression not established
  4. 2009 High

    Quantified the competition between homophilic and heterophilic adhesion and revealed JAM-A's cell-autonomous role in integrin recycling during chemotaxis.

    Evidence Atomic force microscopy adhesion measurements with domain mutants; JAM-A-null neutrophil chemotaxis with β1-integrin co-clustering and internalization assays; triple-KO intravital epistasis

    PMID:18849408 PMID:19118219 PMID:19211506

    Open questions at the time
    • Adaptor linking JAM-A to β1-integrin endosomal trafficking not identified
    • Hierarchy of ICAM-2/JAM-A/PECAM-1 across stimuli not fully mapped
  5. 2012 High

    Identified the phospho-regulatory code of the cytoplasmic tail, with aPKC/PP2A acting on Ser285 to control junction maturation and lumen specification.

    Evidence Direct aPKC-JAM-A binding, S285A phosphomutant, PP2A identification, and 3D cyst morphogenesis assays

    PMID:22371556

    Open questions at the time
    • Downstream effectors of Ser285 phosphorylation not fully defined
    • Interplay with other tail phosphosites not addressed here
  6. 2011 High

    Established JAM-A as a dimerization-dependent brake on epithelial proliferation via Akt/β-catenin inhibition, connecting adhesion to growth control.

    Evidence JAM-A KO mice with β-catenin/TCF reporter, Akt inhibitor rescue, and dimerization-deficient mutant expression

    PMID:21372850

    Open questions at the time
    • Direct molecular link from JAM-A dimerization to Akt not defined
    • Cell-type generality of the proliferation control untested
  7. 2013 High

    Resolved the junctional signaling complex through which JAM-A activates Rap2c and tunes actomyosin contraction to set paracellular permeability.

    Evidence Co-IP defining direct ZO-2 and indirect afadin binding, PDZ-GEF1/Rap2c activation, siRNA epistasis, and RhoA/myosin assays

    PMID:23885123

    Open questions at the time
    • Stoichiometry and dynamics of the ZO-2/afadin/PDZ-GEF1 complex not defined
    • How Rap2c output feeds back on RhoA not detailed
  8. 2014 High

    Separated cis- from trans-dimerization interfaces and showed trans-dimerization is the signaling-competent mode coupling cell confluence to Rap2 activity; identified JAM-A as a strain-specific rotavirus coreceptor.

    Evidence Distinct-interface alanine mutants with AFM and Rap2 assays; antibody/siRNA blocking with VP4 reassortant virus analysis

    PMID:24672055 PMID:25481868

    Open questions at the time
    • Structural basis of NNP-mediated trans-dimerization not solved
    • VP4 region contacting JAM-A not mapped
  9. 2015 High

    Defined JAM-A's role in mitotic spindle orientation, extending its function from junction maintenance to oriented epithelial morphogenesis.

    Evidence JAM-A loss-of-function with live spindle imaging, Cdc42/PI(3)K activity assays, dynactin localization, and 3D cyst culture

    PMID:26306570

    Open questions at the time
    • How JAM-A triggers transient Cdc42 activation at the cortex not resolved
    • Link between PtdIns(3,4,5)P3 gradient and dynactin recruitment not detailed
  10. 2016 High

    Established JAM-A as a tension-sensing receptor that activates RhoA through GEF-H1/p115 RhoGEF in a Ser284-dependent manner.

    Evidence Antibody-bead tension application, RhoA assays, kinase inhibitors, S284 phosphomutant, and GEF siRNA

    PMID:26985018

    Open questions at the time
    • Force-sensing structural element of JAM-A not identified
    • Relationship between Ser284 (tension) and Ser285 (aPKC) phosphorylation not reconciled
  11. 2019 High

    Completed the tyrosine phospho-switch for barrier control by identifying Yes-1 and PTPN13 as the Y280 kinase/phosphatase pair that gates JAM-A–Rap2 coupling under inflammation, and placed JAM-A within tight-junction strand assembly genetically.

    Evidence Phospho-specific antibodies, Yes-1/PTPN13 siRNA, Src inhibitor, Rap2 assays, colitis models; systematic genome-edited combinatorial KO of TJ components with EM

    PMID:30625033 PMID:31467165

    Open questions at the time
    • Crosstalk between Y280 and Ser285/Ser284 phosphorylation events not integrated
    • Direct structural role of JAM-A in strand assembly versus claudins not separated
  12. 2020 High

    Defined the transcriptional and mechanical outputs of JAM-A barrier control: a C/EBP-α→claudin-5 program and a p114RhoGEF/ZO-1 tension axis engaged upon JAM-A loss.

    Evidence JAM-A KO mice with C/EBP-α gain/loss and ChIP at the claudin-5 promoter; ZO-1 FRET tension sensor and traction force microscopy with p114RhoGEF knockdown on variable-stiffness substrates

    PMID:32673519 PMID:32697990

    Open questions at the time
    • How JAM-A activates EPAC upstream of C/EBP-α not mechanistically detailed
    • Trigger that recruits p114RhoGEF upon JAM-A depletion not identified
  13. 2022 High

    Connected JAM-A to the Hippo pathway and to tetraspanin/integrin complexes that enforce contact inhibition and direct collective migration.

    Evidence Co-IP of JAM-A with NF2/LATS1 and dimerization-null mutant epistasis with YAP readout; co-IP/domain mapping of CD9/CD81/αvβ5 and α3β1/CD151/CD9 complexes with Csk pulldown, Src/Rac1 assays, and CIL/migration assays

    PMID:35067832 PMID:35293964 PMID:35602956

    Open questions at the time
    • Direct vs scaffolded nature of JAM-A–NF2/LATS1 interaction not resolved
    • How tetraspanin complexes are spatially coordinated with junctional JAM-A pools unclear
  14. 2023 High

    Showed a cytokine-induced ROCK2/JAM-A complex tightens lymphatic junctions and impairs drainage, with genetic ROCK2 deletion reversing lymphedema.

    Evidence Microfluidic lymphatic drainage-on-chip, ROCK2/JAM-A co-IP, ROCK inhibition, and lymphatic-specific ROCK2 conditional KO mice

    PMID:37782785

    Open questions at the time
    • Structural basis of the ROCK2/JAM-A interaction not defined
    • How this complex relates to the GEF-H1/p115 tension pathway not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple JAM-A cytoplasmic phosphorylation events (Ser284, Ser285, Y280, Thr273) and competing GEF/integrin/tetraspanin partners are integrated into a single context-dependent output remains unresolved.
  • No unified model coupling distinct phosphosites to barrier, mechanics, and proliferation outputs
  • Structural details of trans-dimer and partner complexes largely undefined
  • Tissue-specific selection among competing effector pathways not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098631 cell adhesion mediator activity 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-109582 Hemostasis 3 R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 3 R-HSA-1500931 Cell-Cell communication 2
Partners
AFADINCD9ITGALITGAVNF2PTPN13ROCK2ZO-2
Complex memberships
JAM-A/CASK/PMCA4b sperm flagellar complexJAM-A/CD9/CD81/αvβ5 integrin complexJAM-A/ZO-2/afadin/PDZ-GEF1 junctional complexJAM-A/α3β1/CD151/CD9 complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 JAM-1/F11R is a ligand for the β2 integrin LFA-1; the membrane-proximal Ig-like domain 2 of JAM-1 is required for LFA-1-mediated leukocyte adhesion and transendothelial migration under static and flow conditions. Transfection of JAM-1 into cells combined with LFA-1-dependent adhesion assays under static and physiological flow; domain deletion experiments Nature immunology High 11812992
2002 F11R/JAM-A mediates platelet adhesion to cytokine-inflamed endothelial cells through homophilic interactions; peptides spanning the N-terminal region and first Ig-fold of F11R inhibit this adhesion, identifying those regions as the adhesive interface. Platelet adhesion assays to immobilized recombinant sF11R and to cytokine-stimulated HUVEC; inhibition by recombinant sF11R and domain-specific peptides Thrombosis and haemostasis High 12428104
2002 Two regions of F11R — the N-terminal sequence (S1–C23) and the K70–C82 sequence in the first Ig-fold — are critical for M.Ab.F11-induced platelet aggregation, adhesion, and potentiation; a soluble recombinant sF11R completely inhibits these responses. Peptide inhibition studies of M.Ab.F11-mediated platelet aggregation, adhesion, and potentiation; 3D structure modeling of the extracellular domain Thrombosis and haemostasis Medium 12008956
2003 JAM-1/A and integrin αvβ3 form a complex in quiescent endothelial cells; bFGF treatment causes JAM-1 to redistribute to the cell surface and dissociates the JAM-1/αvβ3 complex, enabling MAP kinase activation required for bFGF-induced angiogenesis. Mutation of the JAM-1 cytoplasmic domain blocks bFGF-induced MAP kinase activation and tube formation. Co-immunoprecipitation; cytoplasmic domain mutagenesis; endothelial cell morphology, proliferation, and tube formation assays; antibody blockade Blood High 12750158
2004 F11R/JAM-A in platelets signals through phosphoinositide-3-kinase activation; M.Ab.F11 crosslinking of F11R with FcγRII induces actin filament assembly, phosphorylation of the 32 and 35 kDa F11R forms, F11R dimerization, and association of F11R with integrin GPIIIa and CD9. Co-immunoprecipitation; phosphorylation assays; wortmannin inhibition; platelet aggregation and spreading assays Journal of receptor and signal transduction research Medium 15344881
2007 JAM-A deficiency in vivo (knockout mice and neutralizing antibody) specifically reduces leukocyte transmigration (but not adhesion) in response to IL-1β or ischemia/reperfusion stimuli, but not to LTB4 or PAF; endothelial-cell JAM-A is the relevant pool; JAM-A and PECAM-1 act sequentially in this transmigration process. Intravital microscopy in JAM-A KO mice and antibody-treated mice; leukocyte transfer experiments; dual blockade/deletion epistasis analysis Blood High 17505016
2007 JAM-A deficiency increases intestinal epithelial permeability in vivo and in vitro, associated with increased expression of claudin-10 and claudin-15 in colonic mucosa and JAM-A siRNA-treated cells. JAM-A knockout mice; dextran flux and transepithelial resistance assays; siRNA knockdown in epithelial cells; Western blot for claudin isoforms The Journal of experimental medicine High 18039951
2007 JAM-A is present on the plasma membrane of sperm flagella; deletion of Jam-A causes flagellar ultrastructural defects and significantly impairs progressive and hyperactivated sperm motility before and after capacitation. Immunolocalization; gene-trap JAM-A knockout mice; sperm motility analysis; electron microscopy of flagellar ultrastructure Developmental biology Medium 18022613
2009 JAM-A on neutrophils is required cell-autonomously for chemotaxis: it concentrates at the leading edge and uropod, is internalized with β1 integrin into endosomal vesicles, and is required for correct internalization and recycling of β1 integrins during migration; clustering of β1 integrin co-clusters JAM-A but not vice versa. JAM-A null neutrophil chemotaxis assays in vivo and in vitro; co-clustering experiments; BAPTA-AM inhibition of integrin internalization; intravital microscopy Journal of cell science High 19118219
2009 LFA-1 binding to domain 2 of JAM-A destabilizes the JAM-A homophilic interaction; the second Ig domain of JAM-A stabilizes the homophilic interaction, and LFA-1 binding to this domain cancels this stabilization; the LFA-1/JAM-A heterophilic interaction is stronger than the JAM-A homophilic interaction. Competitive binding assays; atomic force microscopy adhesion measurements with domain deletion mutants and LFA-1 inserted domain Biophysical journal High 18849408
2009 ICAM-2, JAM-A, and PECAM-1 act sequentially to mediate neutrophil transendothelial migration in a stimulus-dependent manner; when direct neutrophil stimulation is blocked, TNF-α-induced transmigration becomes dependent on all three endothelial molecules. Cell-transfer technique with TNFR-deficient leukocytes; fluorescence intravital microscopy in ICAM-2-/-, JAM-A-/-, PECAM-1-/- mice; analysis of arrest sites Blood High 19211506
2011 JAM-A restricts intestinal epithelial cell proliferation in a dimerization-dependent manner by inhibiting Akt-dependent β-catenin activation; JAM-A-deficient IECs show enhanced β-catenin-dependent transcription, and Akt inhibition reverses colonic crypt hyperproliferation in JAM-A KO mice. JAM-A KO mice; transgenic β-catenin/TCF reporter mice; Akt inhibitor treatment; in vitro dimerization-deficient mutant expression EMBO reports High 21372850
2012 aPKC directly interacts with JAM-A independent of PAR-3 and phosphorylates JAM-A at Ser285; this phosphorylation is required for maturation of cell-cell contacts, tight junction formation, and single lumen specification. Protein phosphatase 2A dephosphorylates JAM-A at Ser285, antagonizing aPKC. Direct binding assays (aPKC–JAM-A); phospho-specific antibodies; non-phosphorylatable JAM-A/S285A mutant expression; 3D cyst culture; PP2A inhibitor/identification The Journal of cell biology High 22371556
2012 JAM-A in resting platelets functions as an endogenous inhibitor of integrin αIIbβ3 outside-in signaling; Jam-A-deficient mice show augmented platelet spreading and clot retraction without changes in inside-out signaling (granule secretion, TxA2 generation, or fibrinogen receptor activation). Jam-A genetic knockout mice; in vivo thrombosis models; ex vivo platelet aggregation, spreading, and clot retraction assays; granule secretion and fibrinogen receptor activation assays Blood High 22271446
2013 JAM-A associates directly with ZO-2 and indirectly with afadin; this complex together with PDZ-GEF1 activates Rap2c; loss of any component increases paracellular permeability. JAM-A also modulates RhoA activity and non-muscle myosin phosphorylation to control apical actomyosin contraction. Co-immunoprecipitation (direct ZO-2 binding, indirect afadin); siRNA knockdown of complex components; paracellular permeability assays; RhoA activity and myosin phosphorylation assays Molecular biology of the cell High 23885123
2013 Mast cell tryptase reduces JAM-A protein expression in intestinal epithelial cells, contributing to decreased transepithelial resistance and increased permeability; tryptase inhibition with nafamostat mesilate rescues JAM-A levels and barrier function. Caco-2 monolayers treated with tryptase; Caco-2/HMC-1 co-culture with mast cell degranulation; TER and FITC-dextran flux; Western blot and immunofluorescence for JAM-A; nafamostat mesilate inhibition The American journal of gastroenterology Medium 23588236
2014 JAM-A functions as a coreceptor for rotavirus entry; JAM-A supports entry of strains RRV, Wa, and UK but not YM; reassortant analysis showed the viral spike protein VP4 determines use of JAM-A as coreceptor. Antibody blocking and siRNA knockdown of JAM-A in MA104 cells; rotavirus infection assays; RRV×YM reassortant virus analysis Virology High 25481868
2014 JAM-A trans-dimerization (between cells) occurs at a site distinct from cis-dimerization (on same cell surface); trans-dimerization requires residues 43NNP45 and activates Rap2 signaling; cis-null but not trans-null JAM-A mutants show enhanced bead clustering; confluent cells with enabled trans-dimerization have enhanced Rap2 activity. Alanine substitution mutants (NNP-JAM-A, cis-null); microsphere aggregation assays; atomic force microscopy; Rap2 activity assays; transfection in confluent vs. sparse cells Molecular biology of the cell High 24672055
2015 JAM-A regulates planar spindle orientation in polarized epithelial cells during mitosis by triggering transient Cdc42 and PI(3)K activation, generating a cortical PtdIns(3,4,5)P3 gradient and organizing cortical F-actin; loss of JAM-A reduces dynactin localization at the cortex, misaligns the spindle, and compromises epithelial morphogenesis in 3D culture. JAM-A KO/knockdown; live-cell imaging of spindle orientation; Cdc42 and PI(3)K activity assays; dynactin localization by immunofluorescence; 3D cyst culture Nature communications High 26306570
2016 Tension applied to JAM-A activates RhoA via GEF-H1 and p115 RhoGEF; activation is PI3K-dependent and regulated by FAK/ERK and Src family kinases respectively; phosphorylation of JAM-A at Ser-284 is required for RhoA activation in response to tension. Mechanical tension applied to JAM-A via antibody-bead system; RhoA activity assays; kinase inhibitors (FAK, ERK, Src, PI3K); S284 phosphomutant expression; GEF-H1 and p115 RhoGEF siRNA Molecular biology of the cell High 26985018
2019 JAM-A tyrosine at Y280 in its cytoplasmic tail is phosphorylated by Yes-1 kinase and dephosphorylated by PTPN13; cytokine exposure (TNFα, IFNγ, IL-22, IL-17A) increases p-Y280 in a Src-dependent manner; Y280 phosphorylation reduces JAM-A association with active Rap2 and impairs barrier function. Phospho-specific antibodies; siRNA knockdown of Yes-1 and PTPN13; Src inhibitor PP2; Rap2 activity assays; TER and dextran flux; colitis patient biopsies and murine colitis model Molecular biology of the cell High 30625033
2019 Claudins and JAM-A coordinately regulate tight junction strand assembly and epithelial polarity; simultaneous deletion of claudins and JAM-A in epithelial cells results in loss of membrane appositions, loss of macromolecule permeability barrier, and sporadic epithelial polarity defects. Systematic genome editing knockout of TJ components (ZO-1/ZO-2, claudins, JAM-A) individually and in combination; electron microscopy; barrier assays; polarity markers The Journal of cell biology High 31467165
2020 JAM-A promotes C/EBP-α expression through suppression of β-catenin transcriptional activity and activation of EPAC; C/EBP-α then directly binds the claudin-5 promoter to drive claudin-5 transcription, reducing endothelial permeability; genetic deletion of JAM-A in mice decreases vascular claudin-5. JAM-A knockout mice; gain/loss-of-function for C/EBP-α; FITC-dextran permeability assays; ChIP/promoter binding of C/EBP-α at claudin-5 promoter; EPAC activation assays; patient tumor biopsies Circulation research High 32673519
2020 JAM-A depletion stimulates junctional recruitment of p114RhoGEF/ARHGEF18, increases mechanical tension on ZO-1 (measured by FRET tension sensor), and increases traction forces at focal adhesions; p114RhoGEF is required for junctional actomyosin activation on stiff but not soft extracellular matrix. ZO-1-based FRET tension sensor; traction force microscopy; JAM-A siRNA depletion; p114RhoGEF knockdown; hydrogels of varying stiffness Cell reports High 32697990
2012 CASK on the sperm flagellum acts as a common PDZ-domain-mediated interacting partner of both JAM-A and PMCA4b; CASK-JAM-A interaction promotes PMCA4b Ca2+ efflux activity, while CASK-PMCA4b interaction inhibits it; in Jam-A null sperm, increased CASK-PMCA4b interaction inhibits PMCA4b, causing Ca2+ accumulation and reduced ATP. Co-immunoprecipitation of CASK with JAM-A and PMCA4b on sperm flagellum; JAM-A KO mice; cytosolic Ca2+ measurement; ATP measurement; PMCA4b enzymatic activity Journal of cellular physiology Medium 22020416
2021 ADAM17 cleaves JAM-A/F11R at the endothelial junction; aging-related increase in ADAM17 expression reduces junctional JAM-A, impairing endothelial wall shear stress mechanosensing; expression of ADAM17-cleavage-resistant JAM-AV232Y rescues impaired mechanosensing both in vitro and in aged mice in vivo. AAV9-mediated ADAM17 overexpression in resistance arteries; ADAM17 activation in cultured endothelial cells under flow; JAM-A knockdown; overexpression of cleavage-resistant JAM-AV232Y mutant; arterial remodeling measurements in aged mice GeroScience Medium 34718985
2022 JAM-A signals through the Hippo pathway to regulate intestinal epithelial proliferation: JAM-A interacts with NF2 and LATS1; JAM-A deficiency increases YAP activity; a dimerization-deficient mutant (JAM-A-DL1) phenocopies JAM-A deficiency, failing to activate Hippo; downstream, EVI1 transcription factor contributes to pro-proliferative gene expression. Co-immunoprecipitation of JAM-A with NF2 and LATS1; YAP activity assays in JAM-A-deficient IEC; overexpression of JAM-A-DL1 vs. JAM-A-WT; EVI1 functional studies iScience Medium 35602956
2022 JAM-A exists in a complex with α3β1 integrin and tetraspanins CD151 and CD9 through its extracellular domain; this complex regulates collective cell migration on laminin and collagen-I substrates but not fibronectin or vitronectin; depletion of any component slows collective migration. Co-immunoprecipitation; domain mapping experiments; MDCK cell siRNA depletion of JAM-A, α3β1, CD151, CD9; collective cell migration assays on different ECM substrates Cellular and molecular life sciences Medium 35067832
2022 JAM-A is part of a multimolecular complex in which tetraspanins CD9 and CD81 link JAM-A to αvβ5 integrin; JAM-A binds Csk and inhibits αvβ5-associated Src activity; loss of JAM-A increases Erk1/2, Abi1, paxillin, and Rac1 activity at contact sites, causing cells to fail contact inhibition of locomotion. Co-immunoprecipitation; JAM-A depletion; Csk pulldown; Src, Erk1/2, Rac1 activity assays; contact inhibition of locomotion video microscopy; αvβ5 integrin engagement experiments The Journal of cell biology High 35293964
2023 A cytokine-induced ROCK2/JAM-A complex in lymphatic endothelial cells mediates junction tightening and impaired lymphatic drainage; lymphatic-specific ROCK2 knockout in mice reverses lymphedema in vivo. Microfluidic lymphatic drainage-on-chip; co-IP of ROCK2 and JAM-A; ROCK isoform characterization; ROCK inhibition; lymphatic-specific ROCK2 conditional KO mice Proceedings of the National Academy of Sciences of the United States of America High 37782785
2010 F11R/JAM-A is expressed in cytokine-stimulated smooth muscle cells (but not in resting SMCs); siRNA silencing of F11R in cytokine-stimulated SMCs blocks both their proliferation and migration, identifying F11R as required for inflamed SMC behavior relevant to atherogenesis. RT-PCR and Western blot for F11R in cytokine-stimulated aortic SMCs; siRNA silencing of F11R; SMC migration and proliferation assays Atherosclerosis Medium 20627246
2011 De novo transcription and translation of F11R in endothelial cells, induced by pro-inflammatory cytokines via NF-κB and JAK/STAT pathways, is required for cytokine-induced insertion of F11R on the EC luminal surface and subsequent platelet adhesion; F11R-specific siRNA and NF-κB/JAK-STAT inhibitors block both F11R upregulation and platelet adhesion. mRNA synthesis inhibitors (actinomycin); NF-κB inhibitor (parthenolide); JAK/STAT inhibitor (AG-480); F11R-specific siRNA transfection; F11R mRNA and protein quantification; platelet adhesion assays Journal of translational medicine Medium 21703019
2007 JAM-A is both essential for and inhibitory to hepatic polarity development in WIF-B cells; the cytoplasmic tail PDZ-binding motif and Thr273 phosphorylation site are required for polarity function; overexpression of wild-type or phosphomutant JAM-A blocks hepatic maturation, while C-terminal truncation is without effect. shRNA knockdown of JAM-A; rescue with RNA-resistant human JAM-A constructs; PDZ-binding motif deletion (huΔC-term) and phosphorylation site point mutants (T273A); hepatic polarity assays in WIF-B cells American journal of physiology. Gastrointestinal and liver physiology Medium 18096610
2004 JAM-1 is recruited to cell-cell contacts in the mouse preimplantation embryo earlier than any other tight junction protein analyzed; at the eight-cell stage it transiently localizes to the apical microvillous pole where PKCζ and PKCδ are found; anti-JAM-1 neutralizing antibodies delayed blastocoel cavity formation without affecting compaction. Immunofluorescence confocal microscopy in staged embryos; anti-JAM-1 neutralizing antibody treatment; comparison with other TJ proteins Journal of cell science Medium 15494378
2013 F11R/JAM-A mRNA is stabilized and retained in the nucleus under hypoxia via ADAR1-mediated RNA editing; hyper-edited mature F11R mRNAs associate with p54nrb and accumulate in the nucleus, preventing export and translation. Hypoxia treatment; ADAR1/ADAR2 knockdown; nuclear/cytoplasmic fractionation; RNA immunoprecipitation with p54nrb; RNA editing analysis PloS one Medium 24147060
2008 Nectin-3, requiring its binding partner afadin, is required for co-localization of JAM-A and claudin-1 at the same cell-cell adhesion membrane domain in L fibroblasts; without nectin-3, JAM-A and claudin-1 form separate adhesion domains. Transfection of L fibroblasts with combinations of JAM-A, claudin-1, nectin-3, E-cadherin; immunofluorescence co-localization analysis; afadin requirement tested Genes to cells Medium 18547333
2022 HOXD11 directly binds to the JAM-A gene promoter to transcriptionally upregulate JAM-A expression; JAM-A in turn activates the NF-κB signaling pathway to promote proliferation, invasion, and migration in esophageal squamous cell carcinoma. ChIP and promoter binding assays for HOXD11 at JAM-A promoter; JAM-A knockdown; NF-κB pathway activity assays; in vitro and in vivo functional assays Human cell Medium 36214988
2022 JAM-A transcriptionally regulates HER2 expression by influencing the binding of transcription factor FOXA1 to a specific site in the HER2 gene promoter; this pathway is unidirectional (JAM-A → FOXA1 → HER2). Targeted disruption of JAM-A, FOXA1, HER2 individually; in silico HER2 promoter analysis; cellular expression studies; correlation in cancer databases Cells Low 35203384

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes. Nature immunology 499 11812992
2007 JAM-A regulates permeability and inflammation in the intestine in vivo. The Journal of experimental medicine 400 18039951
2019 Claudins and JAM-A coordinately regulate tight junction formation and epithelial polarity. The Journal of cell biology 182 31467165
2009 Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1. Blood 153 19211506
2003 Signaling through JAM-1 and alphavbeta3 is required for the angiogenic action of bFGF: dissociation of the JAM-1 and alphavbeta3 complex. Blood 118 12750158
2007 JAM-A mediates neutrophil transmigration in a stimulus-specific manner in vivo: evidence for sequential roles for JAM-A and PECAM-1 in neutrophil transmigration. Blood 112 17505016
2013 Mast cell tryptase reduces junctional adhesion molecule-A (JAM-A) expression in intestinal epithelial cells: implications for the mechanisms of barrier dysfunction in irritable bowel syndrome. The American journal of gastroenterology 107 23588236
2020 JAM-A Acts via C/EBP-α to Promote Claudin-5 Expression and Enhance Endothelial Barrier Function. Circulation research 106 32673519
2013 JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function. Molecular biology of the cell 103 23885123
2004 Contribution of JAM-1 to epithelial differentiation and tight-junction biogenesis in the mouse preimplantation embryo. Journal of cell science 87 15494378
2002 F11-receptor (F11R/JAM) mediates platelet adhesion to endothelial cells: role in inflammatory thrombosis. Thrombosis and haemostasis 82 12428104
2012 aPKC phosphorylates JAM-A at Ser285 to promote cell contact maturation and tight junction formation. The Journal of cell biology 81 22371556
2005 Involvement of JAM-A in mononuclear cell recruitment on inflamed or atherosclerotic endothelium: inhibition by soluble JAM-A. Arteriosclerosis, thrombosis, and vascular biology 79 15681301
2011 JAM-A regulates epithelial proliferation through Akt/β-catenin signalling. EMBO reports 77 21372850
1984 Demonstration of species-specific and cross-reactive components of the adult microsomal antigens from Schistosoma mansoni and S. japonicum (MAMA and JAMA). Journal of immunology (Baltimore, Md. : 1950) 77 6715885
2009 JAM-A promotes neutrophil chemotaxis by controlling integrin internalization and recycling. Journal of cell science 75 19118219
2014 JAM-A and ALCAM are therapeutic targets to inhibit diapedesis across the BBB of CD14+CD16+ monocytes in HIV-infected individuals. Journal of leukocyte biology 73 25420915
2020 Mesenchymal stem-cell-derived exosomal miR-145 inhibits atherosclerosis by targeting JAM-A. Molecular therapy. Nucleic acids 65 33335797
2012 JAM-A protects from thrombosis by suppressing integrin αIIbβ3-dependent outside-in signaling in platelets. Blood 65 22271446
2016 JAM: A Scalable Bayesian Framework for Joint Analysis of Marginal SNP Effects. Genetic epidemiology 63 27027514
2020 Interplay between Extracellular Matrix Stiffness and JAM-A Regulates Mechanical Load on ZO-1 and Tight Junction Assembly. Cell reports 60 32697990
2009 LFA-1 binding destabilizes the JAM-A homophilic interaction during leukocyte transmigration. Biophysical journal 53 18849408
2014 The tight junction protein JAM-A functions as coreceptor for rotavirus entry into MA104 cells. Virology 51 25481868
2013 Overexpression of JAM-A in non-small cell lung cancer correlates with tumor progression. PloS one 51 24265754
2007 Association of plasma levels of F11 receptor/junctional adhesion molecule-A (F11R/JAM-A) with human atherosclerosis. Journal of the American College of Cardiology 51 17964041
2021 Halting the vicious cycle within the multiple myeloma ecosystem: blocking JAM-A on bone marrow endothelial cells restores angiogenic homeostasis and suppresses tumor progression. Haematologica 50 32354870
2014 MicroRNA-495 induces breast cancer cell migration by targeting JAM-A. Protein & cell 50 25070379
2009 Structural determinants of Junctional Adhesion Molecule A (JAM-A) function and mechanisms of intracellular signaling. Current opinion in cell biology 50 19608396
2001 Characterization and chromosomal localization of JAM-1, a platelet receptor for a stimulatory monoclonal antibody. Journal of cell science 50 11171323
2007 JAM-A is present in mammalian spermatozoa where it is essential for normal motility. Developmental biology 48 18022613
2007 The F11 receptor (F11R/JAM-A) in atherothrombosis: overexpression of F11R in atherosclerotic plaques. Thrombosis and haemostasis 47 17264957
2021 The F11 Receptor (F11R)/Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A) in cancer progression. Molecular and cellular biochemistry 46 34533648
2012 A novel role for junctional adhesion molecule-A in tumor proliferation: modulation by an anti-JAM-A monoclonal antibody. International journal of cancer 46 22886345
2006 JAM-A-independent, antibody-mediated uptake of reovirus into cells leads to apoptosis. Journal of virology 45 16415003
2007 Junctional adhesion molecule-A, JAM-A, is a novel cell-surface marker for long-term repopulating hematopoietic stem cells. Blood 43 17986666
2002 Two regions of the human platelet F11-receptor (F11R) are critical for platelet aggregation, potentiation and adhesion. Thrombosis and haemostasis 43 12008956
2015 JAM-A regulates cortical dynein localization through Cdc42 to control planar spindle orientation during mitosis. Nature communications 40 26306570
2010 Poly(I:C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-α via distinct NF-κB pathways in human nasal epithelial cells. Toxicology and applied pharmacology 40 20932985
2004 Signaling pathways of the F11 receptor (F11R; a.k.a. JAM-1, JAM-A) in human platelets: F11R dimerization, phosphorylation and complex formation with the integrin GPIIIa. Journal of receptor and signal transduction research 39 15344881
2003 Junctional adhesion molecule 1 (JAM-1). Journal of biological regulators and homeostatic agents 38 15065765
2020 JAM-A functions as a female microglial tumor suppressor in glioblastoma. Neuro-oncology 37 32592484
2018 Efficient resistance to grass carp reovirus infection in JAM-A knockout cells using CRISPR/Cas9. Fish & shellfish immunology 37 29477498
2016 Tension on JAM-A activates RhoA via GEF-H1 and p115 RhoGEF. Molecular biology of the cell 35 26985018
2005 Genomic structure, organization and promoter analysis of the human F11R/F11 receptor/junctional adhesion molecule-1/JAM-A. Gene 34 16337094
2019 Role of JAM-A tyrosine phosphorylation in epithelial barrier dysfunction during intestinal inflammation. Molecular biology of the cell 33 30625033
2014 Dysregulation of JAM-A plays an important role in human tumor progression. International journal of clinical and experimental pathology 33 25400822
2014 Trans-dimerization of JAM-A regulates Rap2 and is mediated by a domain that is distinct from the cis-dimerization interface. Molecular biology of the cell 32 24672055
2018 JAM-A knockdown accelerates the proliferation and migration of human keratinocytes, and improves wound healing in rats via FAK/Erk signaling. Cell death & disease 30 30154481
2012 CASK interacts with PMCA4b and JAM-A on the mouse sperm flagellum to regulate Ca2+ homeostasis and motility. Journal of cellular physiology 30 22020416
2009 Induction of JAM-A during differentiation of human THP-1 dendritic cells. Biochemical and biophysical research communications 30 19748485
2007 Expression of JAM-A in the human corneal endothelium and retinal pigment epithelium: localization and evidence for role in barrier function. Investigative ophthalmology & visual science 30 17724169
2016 Analysis of the expression and localization of tight junction transmembrane proteins, claudin-1, -4, -7, occludin and JAM-A, in human cervical adenocarcinoma. Histology and histopathology 28 26847087
2006 Expression of JAM-A, AF-6, PAR-3 and PAR-6 during the assembly and remodeling of RPE tight junctions. Brain research 28 16859655
2022 JAM-A interacts with α3β1 integrin and tetraspanins CD151 and CD9 to regulate collective cell migration of polarized epithelial cells. Cellular and molecular life sciences : CMLS 27 35067832
2019 Functional inhibition of F11 receptor (F11R/junctional adhesion molecule-A/JAM-A) activity by a F11R-derived peptide in breast cancer and its microenvironment. Breast cancer research and treatment 27 31650345
2017 Elevated expression of JAM-A promotes neoplastic properties of lung adenocarcinoma. Cancer science 26 28837251
2011 Transcription and translation of human F11R gene are required for an initial step of atherogenesis induced by inflammatory cytokines. Journal of translational medicine 26 21703019
2009 Elevated plasma level of soluble F11 receptor/junctional adhesion molecule-A (F11R/JAM-A) in hypertension. American journal of hypertension 26 19214165
2009 The role of JAM-A in inflammatory bowel disease: unrevealing the ties that bind. Annals of the New York Academy of Sciences 25 19538321
2017 JAM-A overexpression is related to disease progression in diffuse large B-cell lymphoma and downregulated by lenalidomide. Scientific reports 24 28785100
2016 APOC3 induces endothelial dysfunction through TNF-α and JAM-1. Lipids in health and disease 24 27619170
2013 F11R expression upon hypoxia is regulated by RNA editing. PloS one 23 24147060
2015 JAM-A promotes wound healing by enhancing both homing and secretory activities of mesenchymal stem cells. Clinical science (London, England : 1979) 22 25994236
2014 Endothelial JAM-A promotes reovirus viremia and bloodstream dissemination. The Journal of infectious diseases 22 25149763
2019 A peptide antagonist of F11R/JAM-A reduces plaque formation and prolongs survival in an animal model of atherosclerosis. Atherosclerosis 20 30877938
2010 Silencing of the F11R gene reveals a role for F11R/JAM-A in the migration of inflamed vascular smooth muscle cells and in atherosclerosis. Atherosclerosis 20 20627246
2007 JAM-A is both essential and inhibitory to development of hepatic polarity in WIF-B cells. American journal of physiology. Gastrointestinal and liver physiology 20 18096610
2006 Deletion of JAM-A causes morphological defects in the corneal epithelium. The international journal of biochemistry & cell biology 19 17118692
2015 Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma. Mediators of inflammation 18 26556956
2020 microRNA-124 inhibits stem-like properties and enhances radiosensitivity in nasopharyngeal carcinoma cells via direct repression of expression of JAMA. Journal of cellular and molecular medicine 17 32681617
2019 miR-543 promoted the cell proliferation and invasion of nasopharyngeal carcinoma by targeting the JAM-A. Human cell 16 31428943
2013 Cloning and preliminary functional studies of the JAM-A gene in grass carp (Ctenopharyngodon idellus). Fish & shellfish immunology 16 23542603
2005 JAM-A expression during embryonic development. Developmental dynamics : an official publication of the American Association of Anatomists 16 15977176
2023 A 3D biomimetic model of lymphatics reveals cell-cell junction tightening and lymphedema via a cytokine-induced ROCK2/JAM-A complex. Proceedings of the National Academy of Sciences of the United States of America 15 37782785
2022 JAM-A is a multifaceted regulator in hepatic fibrogenesis, supporting LSEC integrity and stellate cell quiescence. Liver international : official journal of the International Association for the Study of the Liver 15 35129269
2019 Antibiotic Tetrocarcin-A Down-regulates JAM-A, IAPs and Induces Apoptosis in Triple-negative Breast Cancer Models. Anticancer research 15 30842150
2015 Ginkgolide B Inhibits JAM-A, Cx43, and VE-Cadherin Expression and Reduces Monocyte Transmigration in Oxidized LDL-Stimulated Human Umbilical Vein Endothelial Cells. Oxidative medicine and cellular longevity 14 26246869
2022 A Transcriptional Link between HER2, JAM-A and FOXA1 in Breast Cancer. Cells 13 35203384
2022 Long non-coding RNA DEPDC1-AS1 promotes proliferation and migration of human gastric cancer cells HGC-27 via the human antigen R-F11R pathway. The Journal of international medical research 13 35466755
2022 JAM-A signals through the Hippo pathway to regulate intestinal epithelial proliferation. iScience 13 35602956
2022 Homophilic Interaction Between Transmembrane-JAM-A and Soluble JAM-A Regulates Thrombo-Inflammation: Implications for Coronary Artery Disease. JACC. Basic to translational science 13 35663628
2021 Aging-induced impaired endothelial wall shear stress mechanosensing causes arterial remodeling via JAM-A/F11R shedding by ADAM17. GeroScience 13 34718985
2017 Epitope characterization of anti-JAM-A antibodies using orthogonal mass spectrometry and surface plasmon resonance approaches. mAbs 13 28933642
2008 Novel role of nectin: implication in the co-localization of JAM-A and claudin-1 at the same cell-cell adhesion membrane domain. Genes to cells : devoted to molecular & cellular mechanisms 13 18547333
2022 A JAM-A-tetraspanin-αvβ5 integrin complex regulates contact inhibition of locomotion. The Journal of cell biology 11 35293964
2022 JAM-A facilitates hair follicle regeneration in alopecia areata through functioning as ceRNA to protect VCAN expression in dermal papilla cells. Precision clinical medicine 11 36132055
2022 HOXD11 upregulates JAM-A and exerts oncogenic properties via NF-κB signaling pathway in esophageal squamous cell carcinoma. Human cell 11 36214988
2020 Generation of Genetically RGD σ1-Modified Oncolytic Reovirus That Enhances JAM-A-Independent Infection of Tumor Cells. Journal of virology 11 32907973
2020 Identification of Novel CDH1-NRG2α and F11R-NRG2α Fusions in NSCLC Plus Additional Novel NRG2α Fusions in Other Solid Tumors by Whole Transcriptome Sequencing. JTO clinical and research reports 11 34589990
2014 Development of new antiatherosclerotic and antithrombotic drugs utilizing F11 receptor (F11R/JAM-A) peptides. Biopolymers 11 24801754
2005 Expression of a recombinant protein of the platelet F11 receptor (F11R) (JAM-1/JAM-A) in insect cells: F11R is naturally phosphorylated in the extracellular domain. Platelets 11 15823866
2019 APOC3 promotes TNF-α-induced expression of JAM-1 in endothelial cell via PI3K-IKK2-p65 pathway. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 10 31004933
2023 Triple negative breast cancer metastasis is hindered by a peptide antagonist of F11R/JAM‑A protein. Cancer cell international 9 37563645
2015 F11R mRNA expression and promoter polymorphisms in patients with rheumatoid arthritis. International journal of rheumatic diseases 9 26230081
2008 Putting the brakes on cancer cell migration: JAM-A restrains integrin activation. Cell adhesion & migration 9 19262151
2024 The Role of ZO-2 in Modulating JAM-A and γ-Actin Junctional Recruitment, Apical Membrane and Tight Junction Tension, and Cell Response to Substrate Stiffness and Topography. International journal of molecular sciences 8 38473701
2017 A novel immunotoxin reveals a new role for CD321 in endothelial cells. PloS one 8 29028806
2010 JAM-A is a novel surface marker for NG2-Glia in the adult mouse brain. BMC neuroscience 8 20184779
2023 F11R/JAM-A: why do platelets express a molecule which is also present in tight junctions? Platelets 7 37246517
2021 Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury. Scientific reports 7 33737554

Missed literature

Know a paper Affinage missed for F11R? Flag it for the maintainers and the community.

No submissions yet.