Affinage

F11R

Junctional adhesion molecule A · UniProt Q9Y624

Length
299 aa
Mass
32.6 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

F11R (JAM-A) is an immunoglobulin-superfamily transmembrane protein that functions as a central organizer of tight-junction assembly, epithelial and endothelial barrier integrity, leukocyte transmigration, and platelet-endothelial adhesion. It forms homophilic cis- and trans-dimers through distinct domains in its two extracellular Ig folds, with trans-dimerization acting as a molecular switch that activates Rap2c via a ZO-2/afadin/PDZ-GEF1 scaffold complex to promote barrier function; aPKC phosphorylation at Ser285 drives JAM-A to mature tight junctions, while Src-family kinase Yes-1 phosphorylation at Tyr280 disrupts Rap2 association and impairs the barrier (PMID:22371556, PMID:24672055, PMID:23885123, PMID:30625033). JAM-A serves as a heterophilic ligand for LFA-1 (via its membrane-proximal Ig domain 2), enabling sequential ICAM-2/JAM-A/PECAM-1-dependent neutrophil diapedesis, and acts as an endogenous inhibitor of integrin αIIbβ3 outside-in signaling in platelets and of αvβ5-associated Src activity via Csk recruitment in epithelial cells (PMID:11812992, PMID:19211506, PMID:22271446, PMID:35293964). Beyond adhesion, JAM-A controls epithelial proliferation through dimerization-dependent activation of the Hippo pathway (NF2/LATS1/YAP) and suppression of Akt/β-catenin signaling, regulates planar spindle orientation via Cdc42/PI3K-generated PIP3 gradients, promotes claudin-5 transcription through an EPAC/C/EBP-α axis in endothelium, and transduces mechanical tension into RhoA activation via GEF-H1 and p115RhoGEF (PMID:35602956, PMID:21372850, PMID:26306570, PMID:32697990, PMID:32673519, PMID:26985018).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 Medium

    Establishing that F11R/JAM-A mediates cell-cell adhesion through homophilic binding answered the question of how this Ig-superfamily protein concentrates at intercellular junctions and supports platelet-endothelial contact.

    Evidence Immunofluorescence of CHO transfectants showing JAM-1 concentration only at transfected–transfected cell contacts; platelet adhesion assay

    PMID:11171323

    Open questions at the time
    • Single lab; no biophysical measurement of binding affinity
    • Cis- vs. trans-dimerization not distinguished
  2. 2002 High

    Identification of JAM-A as a heterophilic ligand for LFA-1 (via Ig domain 2) and mapping of homophilic adhesion sites (N-terminal and first Ig fold) established the dual-mode adhesive logic underlying JAM-A's roles in leukocyte transmigration and platelet adhesion.

    Evidence Adhesion assays under flow with domain-deletion mutants (LFA-1); peptide/soluble-protein inhibition of platelet aggregation and adhesion to HUVEC

    PMID:11812992 PMID:12008956 PMID:12428104

    Open questions at the time
    • No crystal structure of the JAM-A/LFA-1 interface
    • Relative contribution of homophilic vs. heterophilic interactions during in vivo transmigration unknown
  3. 2003 High

    Discovery that JAM-A forms a complex with integrin αvβ3 in quiescent endothelium—dissociated by bFGF signaling to activate MAPK—established JAM-A as a signaling scaffold that couples junctional state to angiogenic responses.

    Evidence Co-immunoprecipitation, JAM-A cytoplasmic-domain mutants, MAP kinase assays, endothelial tube formation

    PMID:12750158

    Open questions at the time
    • Direct binding interface between JAM-A and αvβ3 not mapped
    • Downstream mechanism linking cytoplasmic domain to MAPK not defined
  4. 2004 High

    Demonstration that JAM-A is the earliest tight-junction protein recruited to cell-cell contacts in the preimplantation embryo (8-cell stage), colocalizing with aPKC, and that its blockade delays blastocoel formation established a role in the very first polarization and sealing event in mammalian development.

    Evidence Confocal immunofluorescence of staged mouse embryos; neutralizing-antibody functional assay

    PMID:15494378

    Open questions at the time
    • Molecular basis of early recruitment (before other TJ proteins) not elucidated
    • aPKC-JAM-A phosphorylation relationship not yet tested at this stage
  5. 2007 High

    In vivo knockout and antibody-blockade studies resolved that endothelial (not leukocyte) JAM-A is the critical partner for neutrophil transmigration and acts sequentially with PECAM-1 and ICAM-2, while intestinal JAM-A loss increases mucosal permeability and susceptibility to colitis.

    Evidence Intravital microscopy in JAM-A KO mice with leukocyte transfer; DSS colitis model; barrier assays in KO intestine

    PMID:17505016 PMID:18039951 PMID:19211506

    Open questions at the time
    • Signal from endothelial JAM-A that initiates the transmigration step not identified
    • Whether barrier defects are cell-autonomous vs. secondary to altered claudin expression not fully resolved
  6. 2007 High

    JAM-A KO spermatozoa display flagellar ultrastructural defects and reduced motility, revealing an unexpected role for JAM-A outside classical junctional contexts; JAM-A also marked long-term repopulating hematopoietic stem cells, broadening its functional territory.

    Evidence Gene-trap KO with TEM and CASA sperm motility analysis; competitive bone-marrow transplantation of JAM-A+ sorted cells

    PMID:17986666 PMID:18022613

    Open questions at the time
    • Molecular mechanism linking JAM-A to flagellar structure unknown at this point
    • Functional role of JAM-A on HSCs (beyond marker) not tested
  7. 2009 High

    Biophysical AFM measurements showed that LFA-1 binding to JAM-A domain 2 destabilizes JAM-A homophilic bonds, providing the force-based mechanism by which leukocytes open junctions; concurrently, JAM-A was shown to regulate β1-integrin internalization in neutrophils, linking it to directional migration.

    Evidence Atomic force microscopy with domain mutants; intravital microscopy and chemotaxis assays with JAM-A-null neutrophils

    PMID:18849408 PMID:19118219

    Open questions at the time
    • Structural basis of LFA-1-induced destabilization not resolved at atomic level
    • Whether integrin internalization role generalizes beyond neutrophils untested
  8. 2011 High

    JAM-A was shown to restrain intestinal epithelial proliferation through dimerization-dependent suppression of Akt/β-catenin signaling, directly linking junctional adhesion to growth control.

    Evidence JAM-A KO mice crossed to β-catenin/TCF reporter; Akt inhibitor rescue of crypt hyperproliferation; dimerization-deficient mutants in vitro

    PMID:21372850

    Open questions at the time
    • How JAM-A dimerization biochemically inhibits Akt not defined
    • Whether proliferation effect is Hippo-independent or feeds through it
  9. 2012 High

    aPKC was identified as the kinase phosphorylating JAM-A at Ser285 (dephosphorylated by PP2A), directing JAM-A to tight junctions and controlling single-lumen specification; separately, JAM-A was established as an endogenous inhibitor of integrin αIIbβ3 outside-in signaling in platelets, and CASK was found to link JAM-A to PMCA4b regulation of flagellar Ca²⁺.

    Evidence In vitro kinase assays, S285A mutants in 3D cysts; Jam-A KO platelet spreading/clot retraction vs. inside-out assays; co-IP/PMCA4b activity in KO sperm

    PMID:22020416 PMID:22271446 PMID:22371556

    Open questions at the time
    • aPKC recruitment mechanism to JAM-A (PAR-3-independent) not structurally explained
    • How JAM-A inhibits outside-in signaling at the molecular level unresolved
  10. 2013 High

    Identification of the ZO-2/afadin/PDZ-GEF1 scaffold and Rap2c as the GTPase downstream of JAM-A provided the first complete signaling module linking JAM-A to barrier regulation, complemented by RhoA/actomyosin control.

    Evidence Reciprocal co-IP, siRNA epistasis of each scaffold component, Rap2c and RhoA GTPase activity assays, JAM-A KO mice barrier measurements

    PMID:23885123

    Open questions at the time
    • Stoichiometry and assembly order of the scaffold unknown
    • Whether Rap2c and RhoA arms are independent or cross-regulated not tested
  11. 2014 High

    Dissection of cis- versus trans-dimerization interfaces showed that trans-dimerization (residues 43NNP45) specifically activates Rap2 and induces barrier, establishing trans-dimerization as the contact-dependent molecular switch.

    Evidence Alanine scanning of cis/trans interfaces, AFM, microsphere aggregation, Rap2 GTPase assays in confluent vs. subconfluent cells

    PMID:24672055

    Open questions at the time
    • No high-resolution structure of mammalian JAM-A trans-dimer confirming mutagenesis findings
    • Whether cis-dimerization has separable signaling outputs remains unclear
  12. 2015 High

    JAM-A was found to orient the mitotic spindle in polarized epithelia via transient Cdc42/PI3K activation and cortical PIP3 gradient generation, linking junctional adhesion to tissue architecture maintenance during cell division.

    Evidence JAM-A KO/functional mutant live imaging of spindle, PI3K/Cdc42 activity measurements, dynactin localization, 3D cyst morphogenesis

    PMID:26306570

    Open questions at the time
    • How JAM-A activates Cdc42 transiently and locally not molecularly defined
    • Whether spindle orientation defect contributes to tumorigenesis not tested in vivo
  13. 2016 High

    Direct mechanical tension on JAM-A was shown to activate RhoA through PI3K-dependent GEF-H1 and p115RhoGEF (requiring Ser284 phosphorylation), establishing JAM-A as a junctional mechanosensor.

    Evidence Magnetic bead tension assay, RhoA FRET biosensor, kinase inhibitors, Ser284 phospho-mutant

    PMID:26985018

    Open questions at the time
    • Identity of the kinase for Ser284 in the mechanosensing context not determined
    • Whether mechanotransduction feeds back to Rap2 signaling unclear
  14. 2019 High

    Src-family kinase Yes-1 was identified as the writer and PTPN13 as the eraser for JAM-A Tyr280 phosphorylation, which impairs Rap2 association and barrier function during inflammation—directly linking cytokine signaling to the JAM-A/Rap2 switch in ulcerative colitis tissue.

    Evidence Phospho-specific antibodies, siRNA of Yes-1/PTPN13, co-IP with Rap2, Src inhibitor rescue, human colitis tissue

    PMID:30625033

    Open questions at the time
    • Structural basis of how Y280 phosphorylation disrupts Rap2 binding unknown
    • Whether Y280 and S285 phosphorylation events are coordinated or independent not tested
  15. 2020 High

    Two parallel downstream pathways of JAM-A were elaborated: (1) an EPAC/C/EBP-α axis that transcriptionally activates claudin-5 in endothelium, and (2) a mechanosensitive role upstream of p114RhoGEF/ZO-1 tension regulation that depends on substrate stiffness.

    Evidence JAM-A KO mice with vascular permeability assays, C/EBP-α gain/loss-of-function, ChIP on claudin-5 promoter; FRET ZO-1 tension sensor, traction force microscopy on variable-stiffness substrates

    PMID:32673519 PMID:32697990

    Open questions at the time
    • Whether EPAC/C/EBP-α pathway operates in epithelia beyond endothelium untested
    • How JAM-A depletion triggers p114RhoGEF recruitment molecularly unresolved
  16. 2021 High

    ADAM17 was identified as the sheddase cleaving JAM-A at V232 in aged endothelium under low shear stress, with loss of junctional JAM-A impairing mechanosensing and causing inward arterial remodeling—linking JAM-A shedding to vascular aging.

    Evidence AAV9-ADAM17 overexpression in young mice, cleavage-resistant JAM-AV232Y mutant rescue in vivo, shear stress assays in aged arteries

    PMID:34718985

    Open questions at the time
    • Whether soluble cleaved JAM-A ectodomain has signaling activity not addressed
    • Other sheddases that may contribute in non-endothelial contexts unknown
  17. 2022 High

    JAM-A was placed at the apex of Hippo signaling (via NF2/LATS1 interaction requiring dimerization) and as a Csk-recruiting inhibitor of αvβ5/Src signaling for contact inhibition of locomotion, while its extracellular domain was found to complex with α3β1 integrin and tetraspanins CD9/CD81/CD151 to regulate collective migration.

    Evidence Co-IP of JAM-A with NF2/LATS1, dimerization-deficient mutant phenocopy, YAP/EVI1 readouts; co-IP with Csk and αvβ5, Src/Erk/Rac1 activity in KD; co-IP with α3β1/CD151/CD9 and substrate-specific migration assays

    PMID:35067832 PMID:35293964 PMID:35602956

    Open questions at the time
    • Whether Hippo and Akt/β-catenin pathways are redundant or additive in proliferation control unresolved
    • Structural basis of JAM-A–tetraspanin interaction not defined
  18. 2023 High

    ROCK2 was identified as a JAM-A partner in lymphatic endothelium where inflammation-induced ROCK2/JAM-A complex formation tightens junctions and impedes drainage, revealing a tissue-specific junctional-tightening mechanism distinct from the canonical barrier role.

    Evidence Co-IP of ROCK2 with JAM-A, microfluidic lymphatic chip, lymphatic-specific ROCK2 conditional KO reversing lymphedema in vivo

    PMID:37782785

    Open questions at the time
    • Whether ROCK2 directly phosphorylates JAM-A in this context not tested
    • Generalizability to human lymphedema not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how the multiple phosphorylation events on JAM-A (Ser285, Tyr280, Ser284) are temporally coordinated during junction maturation and inflammation; the high-resolution structural basis of the JAM-A trans-dimer and its heterophilic complexes with integrins, tetraspanins, and Hippo components; whether JAM-A's anti-proliferative functions (Hippo vs. Akt/β-catenin) are synergistic or pathway-specific; and the in vivo significance of soluble JAM-A ectodomain generated by ADAM17 shedding.
  • No integrated phospho-signaling model across Ser285/Tyr280/Ser284
  • No atomic-resolution structures of JAM-A heterophilic complexes
  • Functional significance of shed soluble JAM-A in vivo remains untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 5 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 5 GO:0005929 cilium 2
Pathway
R-HSA-1500931 Cell-Cell communication 5 R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 4 R-HSA-109582 Hemostasis 3 R-HSA-1643685 Disease 2
Partners
CASKCD9ITGA3ITGALITGB3LATS1NF2TJP2
Complex memberships
CD9/CD81/CD151 tetraspanin webNF2/LATS1 Hippo complexROCK2/JAM-A lymphatic complexZO-2/afadin/PDZ-GEF1 scaffold

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 JAM-A (F11R/JAM-1) functions as a ligand for the β2 integrin LFA-1, mediating LFA-1-dependent transendothelial migration of T cells and neutrophils; the interaction requires the membrane-proximal Ig-like domain 2 of JAM-A. Adhesion assays under static and physiological flow conditions, transfectant expression of JAM-A, domain deletion mutants Nature immunology High 11812992
2001 Human JAM-1 (F11R) localizes to cell-cell junctions via homophilic binding; recombinant JAM-1 expressed in CHO cells concentrates at contacts between two transfected cells (not between transfected and untransfected cells), and human platelets specifically bind JAM-1-expressing CHO cell monolayers. Immunofluorescence of CHO transfectants, platelet adhesion assay Journal of cell science Medium 11171323
2002 F11R/JAM-A mediates adhesion of human platelets to cytokine-inflamed endothelial cells through homophilic interactions; the N-terminal region and the 1st Ig-fold of F11R are required, as shown by inhibition with recombinant soluble F11R and peptides spanning those domains. Platelet adhesion assays to immobilized recombinant sF11R and cytokine-stimulated HUVEC; inhibition with domain peptides Thrombosis and haemostasis High 12428104
2002 Two regions of F11R (N-terminal S1–C23 and K70–C82 in the 1st Ig-fold) are critical for M.Ab.F11-induced platelet aggregation, secretion, potentiation, and adhesion; soluble recombinant F11R fully inhibits these responses. Platelet aggregation and adhesion assays with domain-specific peptides and recombinant sF11R; 3D structural modeling of active site Thrombosis and haemostasis High 12008956
2003 JAM-1/A and integrin αvβ3 form a complex in quiescent endothelial cells; bFGF signaling dissociates this complex, redistributes JAM-1 to the cell surface, and requires signaling through the JAM-1 cytoplasmic domain for MAP kinase activation and tube formation. Co-immunoprecipitation, JAM-1 cytoplasmic domain mutations, MAP kinase activation assays, endothelial tube formation assay Blood High 12750158
2004 M.Ab.F11-mediated F11R signaling in platelets requires crosslinking of F11R with FcγRII, leading to actin filament assembly (PI3K-dependent, wortmannin-sensitive), increased intracellular calcium, phosphorylation of F11R (32 and 35 kDa forms), F11R dimerization, and association of F11R with integrin GPIIIa and CD9. Platelet activation assays, PI3K inhibition (wortmannin), co-immunoprecipitation of F11R with GPIIIa and CD9, calcium measurement, phosphorylation analysis Journal of receptor and signal transduction research High 15344881
2004 JAM-1 is recruited to cell-cell contacts in the mouse preimplantation embryo during the 8-cell stage (earlier than any other TJ protein analyzed), transiently localizes to the apical pole during compaction with PKCζ and PKCδ, and anti-JAM-1 neutralizing antibodies delay blastocoel cavity formation by impairing the TJ paracellular seal without affecting global embryo compaction. Immunofluorescence confocal microscopy of staged embryos, neutralizing antibody treatment with functional readout (blastocoel formation) Journal of cell science High 15494378
2007 Endothelial-cell JAM-A (but not leukocyte JAM-A) mediates neutrophil transmigration in response to IL-1β and ischemia/reperfusion injury in vivo; JAM-A and PECAM-1 act sequentially (not additively) to mediate transmigration. Intravital microscopy in JAM-A KO and neutralizing antibody-treated mice; leukocyte transfer to JAM-A-deficient endothelium; dual JAM-A/PECAM-1 blockade Blood High 17505016
2007 JAM-A is present in the plasma membrane of the head and flagellum of mouse spermatozoa; deletion of Jam-A causes flagellar ultrastructural defects, reduced progressive and hyperactivated motility before and after capacitation, and reduced litter size. Gene trap knockout, transmission electron microscopy, sperm motility analysis (CASA), immunofluorescence Developmental biology High 18022613
2007 JAM-A is a cell-surface marker exclusively on long-term repopulating hematopoietic stem cells (LTR-HSC); JAM-A+ cells sorted from whole bone marrow are highly enriched for LTR-HSC activity in transplantation assays. Flow cytometric sorting, colony-forming assays, competitive bone marrow transplantation Blood High 17986666
2009 JAM-A on neutrophils concentrates at the leading edge and uropod; a significant fraction is internalized into endosomal-like vesicles co-distributing with β1 integrin. In JAM-A-null neutrophils, β1 integrin internalization upon chemotactic stimuli is impaired, causing defective uropod retraction and reduced directional migration. Intravital microscopy, in vitro chemotaxis assays with JAM-A-null neutrophils, co-clustering experiments, BAPTA-AM integrin internalization inhibition 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 stabilizes the homophilic bond, and LFA-1 binding to domain 2 reduces homophilic bond strength to that of a domain-2 deletion mutant. The LFA-1/JAM-A heterophilic interaction is stronger than the JAM-A homophilic interaction. Atomic force microscopy adhesion measurements, competitive binding assays, domain deletion mutants of JAM-A Biophysical journal High 18849408
2009 ICAM-2, JAM-A, and PECAM-1 act sequentially to mediate neutrophil transmigration through mouse cremasteric venules in a stimulus-dependent manner; when TNF-α directly stimulates neutrophils, these molecules are dispensable, but when neutrophil TNFR signaling is blocked, transmigration becomes dependent on all three endothelial molecules in sequence. Intravital microscopy, cell transfer with TNFR-KO leukocytes into ICAM-2/JAM-A/PECAM-1 KO recipient mice, site-of-arrest analysis 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 mice show enhanced β-catenin/TCF transcription and colonic crypt hyperproliferation reversible by Akt inhibition. JAM-A KO mice crossed to β-catenin/TCF reporter mice, Akt inhibitor rescue of hyperproliferation, in vitro dimerization-deficient mutant studies EMBO reports High 21372850
2012 aPKC directly interacts with JAM-A in a PAR-3-independent manner and phosphorylates JAM-A at Ser285 upon recruitment to primordial junctions. S285-phosphorylated JAM-A localizes exclusively to tight junctions in polarized cells; S285 phosphorylation is required for functional epithelial barrier formation and single lumen specification in 3D culture. Protein phosphatase 2A dephosphorylates JAM-A at S285. In vitro kinase assay, phospho-specific antibodies, non-phosphorylatable JAM-A/S285A mutant expression, 3D cyst culture, PP2A inhibition 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 enhanced platelet spreading and clot retraction (outside-in), but normal inside-out signaling (granule secretion, TxA2 generation, fibrinogen receptor activation), resulting in enhanced thrombotic function in vivo. Jam-A KO mice, platelet spreading and clot retraction assays (outside-in), granule secretion and aggregation assays (inside-out), intravital thrombosis models Blood High 22271446
2012 On the sperm flagellum, CASK interacts via its PDZ domain alternatively and non-synergistically with either JAM-A or PMCA4b. In the absence of JAM-A, CASK-PMCA4b interaction increases, inhibiting PMCA4b enzymatic activity, causing Ca2+ accumulation and reduced ATP, thus impairing motility. JAM-A positively regulates PMCA4b indirectly through CASK. Co-immunoprecipitation, PMCA4b enzymatic activity assay, Ca2+ and ATP measurements in Jam-A null sperm Journal of cellular physiology High 22020416
2013 JAM-A associates directly with ZO-2 and indirectly with afadin; this complex together with PDZ-GEF1 activates the small GTPase Rap2c to regulate epithelial barrier function. siRNA knockdown of each component phenocopies JAM-A loss (enhanced permeability). JAM-A also modulates RhoA activity and non-muscle myosin phosphorylation to control perijunctional actomyosin contraction. Co-immunoprecipitation, siRNA knockdown of complex components, GTPase activity assays (Rap2c, RhoA), permeability assays, JAM-A KO mice Molecular biology of the cell High 23885123
2014 Trans-dimerization of JAM-A (between adjacent cell surfaces) occurs at a distinct domain from cis-dimerization; residues 43NNP45 in the predicted trans-dimerization site are required. Trans- but not cis-null JAM-A mutants decrease Rap2 activity, and confluent cells (enabling trans-dimerization) show enhanced Rap2 activity, identifying trans-dimerization as a barrier-inducing molecular switch. Transfection of cis- and trans-null JAM-A alanine mutants, microsphere aggregation assays, atomic force microscopy, Rap2 GTPase activity assays, cell confluence experiments Molecular biology of the cell High 24672055
2014 JAM-A serves as a coreceptor for rotavirus entry into MA104 cells; the viral spike protein VP4 determines use of JAM-A as coreceptor, and JAM-A is required for infection by rotavirus strains RRV, Wa, and UK but not YM. Antibody blocking, RRV/YM reassortant virus analysis determining VP4 as the viral determinant, infection assays in MA104 cells Virology High 25481868
2015 JAM-A regulates planar orientation of the mitotic spindle in polarized epithelial cells by triggering transient Cdc42 and PI(3)K activation, generating a cortical PtdIns(3,4,5)P3 gradient and regulating cortical actin; in the absence of functional JAM-A, dynactin localization at the lateral cortex is reduced and the mitotic spindle is misaligned. JAM-A KO/functional mutant cells, live imaging of spindle orientation, PI(3)K and Cdc42 activity measurements, dynactin localization by immunofluorescence, 3D cyst morphogenesis assay Nature communications High 26306570
2016 Mechanical tension imposed on JAM-A activates RhoA via PI3K-dependent activation of GEF-H1 and p115 RhoGEF (further 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. Magnetic bead tension assay on JAM-A, RhoA FRET biosensor, PI3K/FAK/ERK/Src kinase inhibitors, JAM-A Ser284 phospho-mutant expression Molecular biology of the cell High 26985018
2019 During intestinal inflammation, the Src kinase Yes-1 phosphorylates JAM-A at Y280 (cytoplasmic tail), reducing JAM-A association with active Rap2 and impairing barrier function; PTPN13 is the major phosphatase for p-JAM-A Y280. Src kinase inhibitor PP2 rescues cytokine-induced barrier defects. Y280 phosphorylation is increased in ulcerative colitis patient colonic epithelium. Phospho-specific antibodies, kinase/phosphatase siRNA knockdown, co-immunoprecipitation with Rap2, Src inhibitor rescue, human colitis tissue analysis Molecular biology of the cell High 30625033
2019 Claudins and JAM-A coordinately regulate tight junction formation and epithelial polarity; simultaneous deletion of claudins and JAM-A causes loss of membrane appositions, macromolecule permeability barrier, and sporadic epithelial polarity defects, whereas deletion of either alone does not fully recapitulate these phenotypes. Systematic genome editing (CRISPR) of TJ components in epithelial cells; TJ strand ultrastructure, permeability assays, polarity markers The Journal of cell biology High 31467165
2020 JAM-A promotes claudin-5 expression via C/EBP-α transcription factor; JAM-A suppresses β-catenin transcriptional activity and activates EPAC, which increases C/EBP-α expression; C/EBP-α then directly binds the claudin-5 promoter to promote transcription, thereby reducing endothelial permeability. JAM-A KO mice (vascular permeability assays), C/EBP-α gain/loss-of-function, FITC-dextran permeability, β-catenin inhibition, EPAC activation, chromatin studies of claudin-5 promoter, human glioblastoma/ovarian cancer tissue analysis Circulation research High 32673519
2020 JAM-A depletion stimulates junctional recruitment of p114RhoGEF/ARHGEF18, increases mechanical tension on ZO-1 (detected by a ZO-1 tension sensor), and increases traction forces at focal adhesions. p114RhoGEF is required for junctional actomyosin activity and TJ integrity on stiff but not soft ECM, placing JAM-A upstream of p114RhoGEF in mechanosensing. FRET-based ZO-1 tension sensor, traction force microscopy, JAM-A depletion, p114RhoGEF knockdown, variable stiffness ECM substrates Cell reports High 32697990
2021 ADAM17 cleaves JAM-A/F11R at the endothelial junction (at V232, identified by cleavage-resistant mutant JAM-AV232Y) in aged mice and cells exposed to reduced shear stress; loss of junctional JAM-A impairs endothelial wall shear stress mechanosensing, leading to inward hypertrophic arterial remodeling. Overexpression of ADAM17-cleavage-resistant JAM-AV232Y normalizes mechanosensing in aged resistance arteries. AAV9-mediated ADAM17 overexpression in young mice, JAM-A knockdown, cleavage-resistant JAM-AV232Y mutant rescue in vitro and in vivo, shear stress mechanosensing assays in aged mice GeroScience High 34718985
2022 JAM-A interacts with α3β1 integrin and tetraspanins CD151 and CD9 through its extracellular domain to regulate collective cell migration of polarized epithelial cells on laminin and collagen-I substrates; depletion of JAM-A reduces cryptic lamellipodia dynamics in the collective, while JAM-A depletion enhances motility of single cells. MDCK cell JAM-A/integrin/tetraspanin depletion, co-immunoprecipitation, domain mapping, live-cell migration assays, substrate specificity experiments Cellular and molecular life sciences High 35067832
2022 JAM-A forms a multimolecular complex with tetraspanins CD9/CD81 and αvβ5 integrin; JAM-A binds Csk and inhibits αvβ5 integrin-associated Src activity. Loss of JAM-A increases Src downstream signaling (Erk1/2, Abi1, paxillin, Rac1 at cell contacts), increases cell-matrix turnover, and impairs contact inhibition of locomotion (CIL). Co-immunoprecipitation, Src/Erk/Rac1 activity assays, JAM-A KD with CIL functional assay, αvβ5 integrin engagement experiments The Journal of cell biology High 35293964
2022 JAM-A interacts with NF2 and LATS1 to function as an initiator of the Hippo signaling pathway; JAM-A dimerization is required since a dimerization-deficient mutant (JAM-A-DL1) fails to activate Hippo and phenocopies JAM-A deficiency. JAM-A loss or DL1 expression increases YAP activity and EVI1 transcription factor expression to drive intestinal epithelial proliferation. Co-immunoprecipitation (JAM-A with NF2/LATS1), YAP activity assays, dimerization-deficient mutant expression, siRNA knockdown, EVI1 expression analysis in JAM-A KO IEC iScience High 35602956
2023 In lymphatic endothelial cells, inflammatory cytokines induce formation of a ROCK2/JAM-A complex that tightens lymphatic cell-cell junctions and impedes lymphatic drainage; ROCK inhibition loosens lymphatic junctions. Lymphatic-specific ROCK2 knockout reversed lymphedema in mice in vivo. Microfluidic lymphatic-on-chip, co-immunoprecipitation of ROCK2 with JAM-A, ROCK isoform characterization, ROCK2 conditional KO mouse model with lymphedema readout Proceedings of the National Academy of Sciences of the United States of America High 37782785
2013 F11R mRNA levels are increased under hypoxia via ADAR1-mediated RNA editing of the 3'UTR; hyper-edited mature F11R mRNAs are retained in the nucleus via association with p54nrb, preventing cytoplasmic export and translation. RNA editing analysis under hypoxia, ADAR1/ADAR2 siRNA knockdown, nuclear/cytoplasmic fractionation, p54nrb RNA immunoprecipitation PloS one Medium 24147060
2010 F11R is expressed in smooth muscle cells of atherosclerotic arterial intima (not in normal media SMCs); cytokine stimulation induces F11R expression in cultured SMCs, and siRNA silencing of F11R blocks both migration and proliferation of inflamed SMCs. Immunofluorescence of human atherosclerotic arteries, RT-PCR and Western blot in cytokine-stimulated SMCs, siRNA knockdown with migration/proliferation assays Atherosclerosis Medium 20627246
2011 De novo transcription and translation of F11R in endothelial cells, induced by TNF-α/IFN-γ via NF-κB and JAK/STAT pathways, is required for adhesion of human platelets to inflamed endothelium; siRNA silencing of F11R mRNA completely blocks cytokine-induced F11R protein upregulation and platelet adhesion. Transcription/translation inhibitors (actinomycin, parthenolide, AG-480), F11R siRNA knockdown in HUVEC, platelet adhesion assays Journal of translational medicine Medium 21703019
2007 JAM-A regulates permeability and inflammation in the intestinal epithelium; JAM-A-deficient mice show increased mucosal permeability (dextran flux, reduced TER) and altered expression of claudin-10 and claudin-15 in colonic mucosa. JAM-A loss also increases susceptibility to DSS-induced colitis with enhanced epithelial proliferation. JAM-A KO mice, dextran flux and TER measurements, immunoblot for claudins in KO vs. WT, JAM-A siRNA in epithelial monolayers, DSS colitis model The Journal of experimental medicine High 18039951
2022 JAM-A expression transcriptionally regulates HER2 by influencing binding of the transcription factor FOXA1 to a specific site in the HER2 gene promoter in breast cancer cells. JAM-A knockdown with FOXA1 ChIP at HER2 promoter, HER2 expression rescue experiments, promoter reporter assays Cells Medium 35203384
2008 Nectin-3 (via its effector afadin) enables 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. Co-expression of adhesion molecules in L fibroblasts lacking TJs/AJs, immunofluorescence co-localization, afadin requirement demonstrated Genes to cells Medium 18547333

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 398 18039951
2019 Claudins and JAM-A coordinately regulate tight junction formation and epithelial polarity. The Journal of cell biology 179 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 103 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 102 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 78 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 72 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 59 32697990
2009 LFA-1 binding destabilizes the JAM-A homophilic interaction during leukocyte transmigration. Biophysical journal 53 18849408
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
2014 The tight junction protein JAM-A functions as coreceptor for rotavirus entry into MA104 cells. Virology 50 25481868
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 45 22886345
2006 JAM-A-independent, antibody-mediated uptake of reovirus into cells leads to apoptosis. Journal of virology 44 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
2018 Efficient resistance to grass carp reovirus infection in JAM-A knockout cells using CRISPR/Cas9. Fish & shellfish immunology 36 29477498
2020 JAM-A functions as a female microglial tumor suppressor in glioblastoma. Neuro-oncology 35 32592484
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
2014 Dysregulation of JAM-A plays an important role in human tumor progression. International journal of clinical and experimental pathology 33 25400822
1994 Purification and characterization of PAM-1, an integral membrane protein involved in peptide processing. Archives of biochemistry and biophysics 32 8037462
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 31 24672055
2019 Role of JAM-A tyrosine phosphorylation in epithelial barrier dysfunction during intestinal inflammation. Molecular biology of the cell 30 30625033
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
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
2012 CASK interacts with PMCA4b and JAM-A on the mouse sperm flagellum to regulate Ca2+ homeostasis and motility. Journal of cellular physiology 29 22020416
2006 The puromycin-sensitive aminopeptidase PAM-1 is required for meiotic exit and anteroposterior polarity in the one-cell Caenorhabditis elegans embryo. Development (Cambridge, England) 29 17021038
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
2003 Cysteine-rich fibroblast growth factor receptor 1, a new marker for precancerous epithelial lesions defined by the human monoclonal antibody PAM-1. Cancer research 25 12727819
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 23 27619170
2013 F11R expression upon hypoxia is regulated by RNA editing. PloS one 23 24147060
2004 CFR-1 receptor as target for tumor-specific apoptosis induced by the natural human monoclonal antibody PAM-1. Oncology reports 23 15010872
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
2010 The PAM-1 aminopeptidase regulates centrosome positioning to ensure anterior-posterior axis specification in one-cell C. elegans embryos. Developmental biology 17 20599902
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
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
2004 PAM-1, a natural human IgM antibody as new tool for detection of breast and prostate precursors. Human antibodies 15 15719499
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
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 13 37782785
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
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
2021 Aging-induced impaired endothelial wall shear stress mechanosensing causes arterial remodeling via JAM-A/F11R shedding by ADAM17. GeroScience 12 34718985
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 Molecular Dynamics Studies of Poly(Lactic Acid) Nanoparticles and Their Interactions with Vitamin E and TLR Agonists Pam1CSK4 and Pam3CSK4. Nanomaterials (Basel, Switzerland) 11 33167538
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
2020 Generation of Genetically RGD σ1-Modified Oncolytic Reovirus That Enhances JAM-A-Independent Infection of Tumor Cells. Journal of virology 10 32907973
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
2015 F11R mRNA expression and promoter polymorphisms in patients with rheumatoid arthritis. International journal of rheumatic diseases 9 26230081