Affinage

FYB1

FYN-binding protein 1 · UniProt O15117

Length
783 aa
Mass
85.4 kDa
Annotated
2026-04-28
100 papers in source corpus 51 papers cited in narrative 51 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FYB1 (ADAP/SLAP-130) is a hematopoietic-specific scaffolding adapter that couples antigen receptor, integrin, and innate immune receptor signaling to cytoskeletal reorganization, integrin inside-out activation, NF-κB signaling, and transcriptional regulation. Upon TCR or other receptor engagement, FYN-T phosphorylates FYB1 at Y595 and Y651, creating docking sites for the SLP-76 SH2 domain and Nck, thereby nucleating multiprotein signaling complexes containing Ena/VASP, WASP, and SKAP55 that drive actin polymerization, SLP-76 microcluster assembly, and—via SKAP55-mediated recruitment of Rap1/RIAM/RAPL and talin/kindlin-3—LFA-1 and αIIbβ3 integrin clustering and activation (PMID:10570256, PMID:10747096, PMID:11567141, PMID:17403904, PMID:24523237). A separable ADAP domain recruits the CARMA1–BCL10–MALT1 complex and TAK1 to activate NF-κB independently of its integrin function, while phospho-Y571 mediates ZAP70 binding for chemokine-directed migration and primes STAT3 for TLR4-driven macrophage polarization (PMID:17478723, PMID:20164171, PMID:26246585, PMID:33431658). Loss-of-function mutation in FYB1 causes autosomal recessive small-platelet thrombocytopenia in humans, consistent with its essential role in megakaryocyte polarization and proplatelet formation (PMID:25876182, PMID:29950291).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1997 High

    Identification of FYB as a hematopoietic adapter bridging FYN and SLP-76 established the molecular framework for understanding how TCR-proximal kinase signals are relayed through scaffold-mediated protein complexes.

    Evidence cDNA cloning, co-immunoprecipitation, yeast two-hybrid, and IL-2 reporter assays in T cell hybridomas and Jurkat cells

    PMID:9115214 PMID:9207119

    Open questions at the time
    • Endogenous stoichiometry of FYB–SLP-76–FYN ternary complex unknown
    • Positive vs. negative regulatory role on IL-2 unresolved between overexpression systems
  2. 1998 High

    Discovery that SKAP55 binds FYB via its SH3 domain defined the ADAP/SKAP55 module as a stable signaling unit, raising the question of what downstream effectors this module controls.

    Evidence Yeast two-hybrid, reciprocal co-immunoprecipitation in T cells, confocal co-localization

    PMID:9671755 PMID:9748251

    Open questions at the time
    • Functional consequence of SKAP55–FYB association not yet established
    • Whether SKAP55 stability depends on FYB binding unknown
  3. 1999 High

    Mapping Y595 and Y651 as FYN-T phosphorylation sites mediating SLP-76 SH2 binding, and showing their requirement for synergistic IL-2 upregulation, established that specific FYB phosphotyrosines are the critical signaling nodes rather than the FYB–FYN interaction itself.

    Evidence Site-directed mutagenesis, co-immunoprecipitation, IL-2 promoter reporter in Jurkat T cells

    PMID:10409671 PMID:10570256

    Open questions at the time
    • Whether additional phosphosites have non-redundant roles unknown
    • In vivo relevance of individual phosphosites not tested
  4. 2000 High

    Linking FYB to Ena/VASP and WASP at the T cell–APC interface revealed how FYB couples TCR signaling to actin cytoskeletal remodeling, while integrin stimulation studies showed FYB participates in β1 integrin-driven migration, broadening its role beyond TCR signaling.

    Evidence EVH1 domain binding assays, co-immunoprecipitation, confocal microscopy at bead interfaces, dominant-negative perturbation of actin polymerization, migration assays through fibronectin

    PMID:10640723 PMID:10747096

    Open questions at the time
    • Whether FYB–Ena/VASP interaction is direct or bridged by SLP-76 in vivo unclear
    • Relative contributions of Ena/VASP vs. WASP pathways not resolved
  5. 2001 High

    Genetic knockout of ADAP demonstrated its essential, non-redundant role in TCR-induced integrin (LFA-1) clustering and T cell proliferation—but not actin polymerization—definitively establishing ADAP as the bridge between TCR signaling and integrin inside-out activation in vivo.

    Evidence Two independent ADAP knockout mouse lines with LFA-1 clustering, actin polymerization, proliferation, and in vivo immune response assays

    PMID:11567140 PMID:11567141

    Open questions at the time
    • Molecular mechanism by which ADAP enables integrin clustering not yet identified
    • Whether ADAP functions identically in all hematopoietic lineages unclear
  6. 2001 Medium

    Extension of ADAP function to mast cell FcεRI-driven adhesion and degranulation, and to macrophage FcγR-mediated phagocytosis, established ADAP as a general hematopoietic integrin–actin coupling adapter beyond T cells.

    Evidence Overexpression in RBL-2H3 mast cells with adhesion/degranulation assays; co-IP and phagocytosis assays in macrophages

    PMID:11553777 PMID:11739662

    Open questions at the time
    • Mast cell studies relied on overexpression rather than loss-of-function
    • Whether ADAP-independent pathways compensate in phagocytes unknown
  7. 2004 High

    NMR structure of the ADAP C-terminal hSH3 domain revealed an atypical helically-extended SH3 fold incapable of binding proline-rich ligands, redirecting the search for its binding partners toward non-canonical interactions.

    Evidence NMR structure determination with functional validation of lost polyproline binding

    PMID:15062083

    Open questions at the time
    • Physiological ligand of the hSH3 domain unresolved at this time
    • Whether lipid binding (later discovered) is the primary hSH3 function unknown
  8. 2005 High

    Discovery that the hSH3 domain binds phosphoinositides (PIP2/PIP3) via basic patches, and that ADAP stabilizes SKAP55 protein by preventing its rapid proteolysis, defined two new mechanistic roles—membrane targeting and chaperone-like stabilization—explaining how the ADAP/SKAP55 module is maintained and positioned.

    Evidence Liposome sedimentation, NMR mapping, mutagenesis of basic residues; cycloheximide chase in ADAP-deficient Jurkat cells with SKAP55 half-life measurement

    PMID:15843031 PMID:15849195

    Open questions at the time
    • In vivo relevance of hSH3-lipid binding not demonstrated
    • Whether SKAP55 degradation pathway (proteasome vs. lysosome) defined
  9. 2006 High

    Demonstration that the ADAP/SKAP55 module recruits Rap1-GTP to the plasma membrane via RIAM, and that membrane-targeted ADAP/SKAP55 suffices to induce adhesion without TCR stimulation, identified the molecular mechanism by which ADAP activates integrins.

    Evidence Rap1 subcellular fractionation, membrane-targeted constructs, RIAM co-IP, adhesion and conjugate formation assays in T cells

    PMID:16980616 PMID:17403904

    Open questions at the time
    • Which signals trigger ADAP/SKAP55 membrane translocation in the first place unclear
    • Contribution of RAPL vs. RIAM pools not yet separated
  10. 2007 High

    Identification of a separable ADAP domain that recruits the CARMA1–BCL10–MALT1 complex to activate NF-κB—independent of its integrin function—revealed ADAP as a bifunctional adapter with distinct structural modules for adhesion and transcriptional signaling.

    Evidence ADAP knockout T cells, NF-κB EMSA/reporter, IκB phosphorylation, CARMA1–BCL10–MALT1 co-IP, domain mapping mutants

    PMID:17478723

    Open questions at the time
    • How ADAP is directed to NF-κB vs. integrin signalosomes not resolved
    • Whether NF-κB function requires prior ADAP phosphorylation unknown
  11. 2010 High

    Dissecting the two-site model (CARMA1-binding and TAK1-binding) for ADAP-mediated NF-κB activation, and comprehensive phosphoproteomic mapping of ADAP interactors, provided a detailed molecular wiring diagram of ADAP's signaling outputs.

    Evidence Domain mutants in ADAP-deficient T cells with IKK phosphorylation/ubiquitination readouts; SILAC/18O phosphopeptide pulldowns from Jurkat lysates

    PMID:20164171 PMID:20568816 PMID:20661443

    Open questions at the time
    • Structural basis of ADAP–CARMA1 and ADAP–TAK1 interactions unknown
    • Relative quantitative contribution of each phosphosite in primary T cells not established
  12. 2011 High

    Mechanistic dissection of integrin activation showed ADAP/SKAP55 operates through two parallel effector pools (RAPL/Mst1 and RIAM/kindlin-3) for LFA-1 affinity/avidity control, and that the SKAP55-PH domain (R131) restricts ADAP from the NF-κB signalosome, providing a structural basis for functional bifurcation.

    Evidence ADAP/SKAP55-deficient mice with in vivo homing, intravital microscopy, co-IP of dual effector complexes; SKAP-ADAP chimera and PH-domain mutant reconstitution

    PMID:21525391 PMID:21536650 PMID:22117043

    Open questions at the time
    • How the two effector pools are spatially segregated in the cell unclear
    • Whether post-translational modifications switch ADAP between pools unknown
  13. 2013 High

    Biophysical demonstration that multipoint ADAP–SLP-76 SH2 binding oligomerizes SLP-76 into microclusters explained how ADAP acts as a polyvalent scaffold for signalosome assembly, while Fyn–ADAP was shown to selectively control NK cell cytokine production via CARMA1–BCL10–MAP3K7.

    Evidence Analytical ultracentrifugation/SPR of SLP-76 SH2–ADAP, microcluster imaging with combinatorial mutants; Fyn/ADAP double KO NK cells with cytotoxicity vs. cytokine dissection

    PMID:23979596 PMID:24036998

    Open questions at the time
    • Stoichiometry of the SLP-76 oligomer in living cells unknown
    • Whether Fyn–ADAP complex in NK cells uses same phosphosites as T cells untested
  14. 2014 High

    Identification of distinct ADAP regions that separately bind talin and kindlin-3, both required for full αIIbβ3 activation in platelets, defined the molecular mechanism of ADAP-dependent integrin activation in the hemostatic system.

    Evidence GST pulldown domain mapping, proximity ligation assay, reconstitution in CHO cells, ADAP KO platelet integrin activation assay

    PMID:24523237

    Open questions at the time
    • Whether talin and kindlin-3 bind ADAP simultaneously or sequentially unknown
    • Crystal structure of ADAP–talin and ADAP–kindlin interfaces not available
  15. 2015 High

    A human nonsense mutation in FYB1 causing autosomal recessive small-platelet thrombocytopenia established FYB1 as a disease gene, while mechanistic work showed ADAP loss impairs megakaryocyte polarization and proplatelet release, and that ADAP/SKAP55 modulates PD-1 expression on CD8+ T cells via Fyn–Ca²⁺–NFATc1.

    Evidence Homozygosity mapping/exome sequencing in patient family, platelet morphology and activation assays; MK-specific KO mice with 3D imaging; ADAP/SKAP55 KO mice in tumor models with PD-1 flow cytometry

    PMID:25851535 PMID:25876182 PMID:29950291

    Open questions at the time
    • Whether other FYB1 mutations cause thrombocytopenia in additional families not reported
    • Mechanism linking ADAP to NFATc1 nuclear translocation for PD-1 not fully defined
  16. 2015 High

    Discovery that ZAP70 binds ADAP at pY571 via its N-terminal SH2 domain, with Y571 selectively required for chemokine-directed migration but not TCR-dependent adhesion, revealed a third functional axis of ADAP phosphorylation distinct from integrin and NF-κB functions.

    Evidence SILAC proteomics, NMR mapping, microscale thermophoresis (Kd 2.3 µM), Y571F mutant functional assay

    PMID:26246585

    Open questions at the time
    • Whether ZAP70–ADAP interaction occurs in non-T cells unknown
    • Downstream effectors of Y571-ZAP70 pathway for migration not identified
  17. 2018 High

    Live-cell imaging revealed ADAP pre-positions at TCR contact sites before SLP-76, with non-phosphorylated ADAP enriching in actin protrusions to seed nascent SLP-76 oligomers, revising the model from ADAP as a passive substrate to an upstream organizer of signalosome assembly.

    Evidence Phospho-specific anti-pY595 antibody live imaging, ADAP point mutants, SLP-76 microcluster kinetics analysis

    PMID:30305305

    Open questions at the time
    • What targets non-phosphorylated ADAP to actin protrusions remains unknown
    • Whether upstream ADAP positioning involves hSH3-lipid interactions not tested
  18. 2021 Medium

    Extension of ADAP pY571 function to innate immunity showed ADAP primes STAT3 for TLR4-mediated activation in macrophages, controlling M1/M2 polarization, revealing an unexpected role for a classically lymphocyte-associated adapter in macrophage transcriptional programming.

    Evidence ADAP-/- macrophages, Y571F mutant, ADAP–STAT3 co-IP, STAT3 phosphorylation, macrophage polarization assay

    PMID:33431658

    Open questions at the time
    • Whether ADAP directly binds STAT3 or requires an intermediary not resolved
    • Whether this pathway operates in human macrophages untested
  19. 2022 Medium

    Discovery that ADAP competes with STAT1 for importin-α5 binding, restraining STAT1 nuclear entry and FcγRI/IV transcription, explained the thrombocytopenic phenotype in ADAP-deficient mice through enhanced macrophage-mediated platelet phagocytosis and identified a pharmacologically targetable axis.

    Evidence ADAP KO mice, competition co-IP of ADAP–STAT1–importin-α5, FcγR transcription, phagocytosis assay, pharmacological STAT1 inhibitor rescue

    PMID:35637282

    Open questions at the time
    • Whether ADAP–importin-α5 interaction is direct or STAT1-mediated not fully resolved
    • Relevance to human ITP not established
  20. 2024 Medium

    Identification of ADAP as a selective RIG-I interactor that suppresses RIG-I ISGylation to promote IRF3/TBK1 signaling and IFN-β production extended ADAP's role to antiviral innate immunity, demonstrating it modulates post-translational modification of pattern recognition receptors.

    Evidence Co-IP of ADAP–RIG-I, ISGylation assay, IRF3/TBK1 phosphorylation, ADAP-/- macrophages and mice with RNA virus infection

    PMID:38776321

    Open questions at the time
    • Mechanism by which ADAP suppresses ISGylation unknown
    • Whether ADAP–RIG-I interaction requires ADAP phosphorylation not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Outstanding questions include the structural basis for ADAP's multivalent scaffold function (no full-length structure exists), how ADAP is partitioned among its functionally distinct pools (integrin, NF-κB, STAT3, RIG-I) within a single cell, and whether its innate immune functions (STAT1/STAT3/RIG-I regulation) are mechanistically linked or fully independent pathways.
  • No full-length or near-full-length ADAP structure available
  • Mechanism directing ADAP to distinct signaling pools not defined
  • Whether ADAP's innate immune functions are conserved in human macrophages not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0008092 cytoskeletal protein binding 3 GO:0008289 lipid binding 1
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 6 R-HSA-109582 Hemostasis 4 R-HSA-1500931 Cell-Cell communication 4 R-HSA-162582 Signal Transduction 4
Partners
CARMA1FYNNCK1RIAMSKAP55SLP76WASPZAP70
Complex memberships
ADAP/SKAP55 moduleCARMA1-BCL10-MALT1 (CBM) complex

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 FYB (p120/130) was cloned as a hematopoietic-specific adapter that associates with the Src kinase p59(Fyn) via direct binding, associates with SLP-76 via the SLP-76 SH2 domain, is tyrosine-phosphorylated upon TCR/CD3 ligation, and augments IL-2 secretion from T cell hybridomas in response to TCR stimulation. cDNA cloning, co-immunoprecipitation, yeast two-hybrid, overexpression in T cell hybridoma with IL-2 readout Proceedings of the National Academy of Sciences of the United States of America High 9207119
1997 SLAP-130 (FYB) was cloned as a SLP-76-associated phosphoprotein that binds the SH2 domain of SLP-76, is a substrate of TCR-induced protein tyrosine kinases, and when overexpressed diminishes TCR-induced IL-2 promoter activity and interferes with SLP-76 augmentation of IL-2 promoter activity, suggesting it acts as a negative regulator recruited by SLP-76. Molecular cloning, co-immunoprecipitation with SLP-76 SH2 domain, co-transfection/reporter assay in Jurkat cells The Journal of biological chemistry High 9115214
1998 FYB binds SKAP55 and SKAP55R through the SH3 domains of those proteins interacting with proline-rich sequences in FYB; FYB and SKAP55 colocalize in the perinuclear region; both SKAP55 and SKAP55R are FYN kinase substrates in T cells. Yeast two-hybrid screen with FYB as bait, co-immunoprecipitation in T cells, confocal immunofluorescence microscopy Proceedings of the National Academy of Sciences of the United States of America High 9671755
1998 SLAP-130 (FYB) directly associates with SKAP55 via the SH3 domain of SKAP55 binding a proline-rich sequence of SLAP-130; both proteins are components of the Fyn complex in human T cells. Co-immunoprecipitation in COS cells and human T cells, co-transfection of truncation mutants, yeast two-hybrid The Journal of biological chemistry High 9748251
1999 FYN-T selectively phosphorylates FYB, creating docking sites for FYN-T and SLP-76 SH2 domains; co-expression of all three components (FYN-T, FYB, SLP-76) synergistically up-regulates TCR-driven IL-2 transcription; FYB phosphorylation shows distinct cytoplasmic localization and long-term stable kinetics. In vitro kinase assay with FYN-T, co-immunoprecipitation, co-transfection/IL-2 promoter luciferase reporter assay The Journal of biological chemistry High 10409671
1999 Tyrosines Tyr595 and Tyr651 of FYB are the major FYN-T phosphorylation sites that mediate binding to the SLP-76 SH2 domain; the synergistic IL-2 promoter upregulation by FYN-T-FYB-SLP-76 requires FYB–SLP-76 interaction at these sites but not the FYB–FYN-T interaction. Site-directed mutagenesis of FYB tyrosines, co-immunoprecipitation in Jurkat T cells, IL-2 promoter reporter assay Journal of immunology High 10570256
1999 A novel 130 kDa isoform of FYB (FYB-130) was identified containing a 46 amino acid insertion in the C-terminal region; both FYB-120 and FYB-130 bind SH2 domains of FYN-T and SLP-76, are FYN-T substrates, and localize to the cytoplasm and nucleus; FYB-130 more efficiently up-regulates anti-CD3-driven NF-AT transcription when co-expressed with FYN-T and SLP-76; FYB gene maps to human chromosome 5p13.1. cDNA cloning, co-immunoprecipitation, fluorescence in situ hybridization, NF-AT reporter assay in T cells The Journal of biological chemistry Medium 10497204
2000 FYB/SLAP was identified as a ligand for Ena/VASP homology 1 (EVH1) domains; upon TCR engagement, FYB/SLAP localizes at the T cell–APC interface alongside Evl, WASP, and Arp2/3; FYB/SLAP associates with Ena/VASP proteins and is present in complexes with WASP, Nck, and SLP-76; inhibition of FYB/SLAP–Ena/VASP or WASP–Arp2/3 binding impairs TCR-dependent actin rearrangement. EVH1 domain binding assay, co-immunoprecipitation, confocal microscopy/localization at bead interface, perturbation by dominant-negative constructs measuring actin polymerization The Journal of cell biology High 10747096
2000 alpha4beta1 integrin stimulation of T cells causes tyrosine phosphorylation of SLAP-130/FYB and enhances its association with p59fyn SH2 domain; overexpression of SLAP-130/FYB enhances T cell migration through fibronectin-coated filters in response to SDF-1alpha, identifying FYB as a substrate and regulator in beta1 integrin signaling. Integrin stimulation, immunoprecipitation with phosphotyrosine antibody, migration assay through fibronectin filters, overexpression in primary T cells Journal of immunology Medium 10640723
2000 Overexpression of SLAP-130 abrogates SLP-76 rescue of signaling in SLP-76-deficient Jurkat cells specifically for TCR-induced ERK activation but not PLCgamma1 phosphorylation; tyrosine 559 of SLAP-130 is critical for the SLP-76 interaction and for SLAP-130's negative regulatory effect on SLP-76 function. Co-transfection rescue assay in SLP-76-deficient Jurkat cells, deletion and point mutants of SLAP-130, co-immunoprecipitation The Journal of biological chemistry Medium 10671560
2001 T cells from SLAP-130/FYB (ADAP) knockout mice show markedly impaired proliferation after CD3 engagement; TCR-stimulated clustering of integrin LFA-1 is defective in SLAP-130/FYB-deficient cells whereas TCR-induced actin polymerization is normal; SLAP-130/FYB couples TCR-mediated cytoskeletal rearrangement to integrin LFA-1 clustering and activation. Genetic knockout mouse model, T cell proliferation assay, LFA-1 clustering by microscopy, actin polymerization assay Science High 11567141
2001 Fyb/Slap-deficient T cells exhibit defective proliferation and cytokine production; Fyb/Slap has no role in F-actin polymerization or TCR clustering but is required for TCR-induced integrin clustering and adhesion; Fyb/Slap is required in vivo for T cell-dependent immune responses. Genetic knockout mouse model, proliferation assay, cytokine measurement, integrin clustering assay, F-actin polymerization assay, in vivo immune response Science High 11567140
2001 FYB up-regulates integrin-mediated adhesion to fibronectin and mediator (beta-hexosaminidase) release in RBL-2H3 mast cells upon FcepsilonRI aggregation; the FYB SH3 domain is required for mediator release but not adhesion; FcepsilonRI aggregation increases FYB tyrosine phosphorylation; FYB colocalizes with F-actin in membrane ruffles. Overexpression in RBL-2H3 mast cells, adhesion assay to fibronectin, beta-hexosaminidase release assay, SH3 domain deletion mutants, confocal immunofluorescence Proceedings of the National Academy of Sciences of the United States of America Medium 11553777
2001 Upon induction of phagocytosis, a large molecular complex containing Fyb/SLAP, Ena/VASP proteins, SLP-76, Nck, and WASP is assembled in macrophages; Fyb/SLAP activation of Fcgamma receptors leads to recruitment of VASP and profilin; a second Nck pathway recruits WASP; these converge to regulate actin polymerization required for pseudopod extension and particle ingestion. Co-immunoprecipitation, confocal microscopy of phagosome formation, phagocytosis efficiency assay in primary and immortalized macrophages Journal of cell science High 11739662
2001 FYB (ADAP) promotes beta1 integrin clustering on mast cells in a selective manner (FcepsilonRI clustering is unaffected), extending ADAP's modulatory role from beta2 to beta1 integrins. Overexpression of ADAP in mast cells, flow cytometry assessment of beta1 integrin and FcepsilonRI clustering kinetics Biochemical and biophysical research communications Medium 11741310
2003 The Yersinia phosphatase YopH interacts with Fyb in macrophages via both phosphotyrosine-dependent and phosphotyrosine-independent mechanisms; YopH dephosphorylates Fyb; mutants unable to bind p130Cas/Fyb fail to localize to focal complexes in infected cells and are attenuated in virulence, demonstrating Fyb phosphorylation is biologically relevant in Yersinia infection. YopH mutant analysis in infected cells, immunofluorescence co-localization, virulence attenuation assay, phosphatase activity measurement Cellular microbiology Medium 12542470
2003 MIST directly associates with SLAP-130 via the MIST SH2 domain; collaboration of SLAP-130 with SKAP55 is required for recruitment of MIST to Lyn in mast cells; MIST is preferentially recruited to Fyn rather than Lyn, regulated by higher affinity of SLAP-130/SKAP55 for Fyn-SH2 versus Lyn-SH2. Co-immunoprecipitation in mast cell lines, binding assays with SH2 domain constructs FEBS letters Medium 12681493
2004 The C-terminal domain of ADAP (FYB/SLAP-130) was solved by NMR spectroscopy and found to represent an altered SH3 domain fold (helically extended SH3, hSH3) in which an N-terminal amphipathic helix contacts the regular SH3 fold, creating a composite surface that can no longer bind conventional proline-rich peptides. NMR structure determination of ADAP C-terminal domain Structure High 15062083
2004 ADAP-SLP-76 binding differentially regulates pSMAC formation versus T cell-APC conjugation: mutation of YDDV sites in ADAP (M12) prevents SLP-76 SH2 binding and acts as dominant negative for pSMAC formation and IL-2 production, but has distinct effects on conjugation; ADAP colocalizes with LFA-1 at the immunological synapse. Mutational analysis of ADAP YDDV sites, T cell-APC conjugation assay, microscopy of immunological synapse/SMAC formation, IL-2 production assay The Journal of experimental medicine High 15477347
2005 The hSH3 domain of ADAP binds acidic lipids including phosphatidylinositides (PIP2, PIP3); positively charged surface patches of the domain preferentially bind polyvalent acidic lipids; the N-terminal helix is required for lipid binding; this identifies the hSH3 as a novel lipid interaction domain suggesting ADAP directly interacts with phosphoinositide-enriched plasma membrane regions. In vitro lipid binding assays (liposome sedimentation, lipid overlay), site-directed mutagenesis of basic residues, NMR mapping Journal of molecular biology High 15843031
2005 SKAP55 protein is unstable in ADAP-deficient Jurkat T cells and is protected from rapid proteolysis (~15-20 min half-life) by ADAP binding via the SKAP55 SH3 domain; ADAP restores SKAP55 expression by decreasing its proteolysis rate ~5-fold; the SKAP55 SH3 domain (which mediates SKAP55-ADAP association) is required for ADAP's protective effect. ADAP-deficient Jurkat cell line, SKAP55 half-life measurement by cycloheximide chase, rescue by ADAP reconstitution, SH3 domain mutants The Journal of biological chemistry High 15849195
2005 FYB (Fyb) interacts with mammalian actin-binding protein 1 (mAbp1) via the mAbp1 SH3 domain binding the Fyb N-terminal region; the interaction is detected in macrophage lysates and both proteins co-localize with F-actin at the leading edge. Yeast two-hybrid screen with Fyb domains as bait, co-immunoprecipitation in macrophage lysates, co-localization by immunofluorescence FEBS letters Medium 15848169
2005 ADAP associates with c-Src in osteoclast precursors and RAW264 cells; c-Src kinase activity and SH2 domain are required for this association; Tyr807 in the ADAP C-terminus is a major c-Src recognition site; ADAP tyrosine phosphorylation is integrin-dependent and Src kinase-dependent; ADAP-knockdown cells show retarded migration and impaired multinucleated cell (osteoclast) formation. Pull-down/mass spectrometry identification, co-immunoprecipitation with c-Src, siRNA knockdown, migration and fusion assays The Journal of biological chemistry Medium 16020549
2006 The ADAP/SKAP55 signaling module is required for TCR-mediated integrin activation; ADAP/SKAP55 interaction is mandatory; disruption of the module displaces the small GTPase Rap1 from the plasma membrane without affecting its GTPase activity; membrane-targeted ADAP/SKAP55 induces T cell adhesion in the absence of TCR stimulation. Dominant-negative and membrane-targeted constructs, Rap1 localization by subcellular fractionation and microscopy, adhesion assays, GTPase activity measurement Molecular and cellular biology High 16980616
2006 ADAP is required for normal alphaIIbbeta3 activation in platelets downstream of VWF/GP Ib-IX-V and other agonists (ADP, PAR4); ADAP stabilizes SKAP-HOM expression via interaction with SKAP-HOM SH3 domain; ADAP-deficient mice show increased rebleeding from tail wounds and reduced stable adhesion under shear flow. ADAP knockout mice, fibrinogen/ligand-mimetic binding assay, flow cytometry of integrin activation, tail bleeding assay, shear flow adhesion assay Blood High 17003372
2007 ADAP regulates TCR-mediated NF-kappaB activation; ADAP-deficient T cells show impaired NF-kappaB nuclear translocation, reduced IkappaB degradation/phosphorylation, and impaired CARMA1-BCL-10-MALT1 complex assembly; a distinct region of ADAP is required for CARMA1 association and NF-kappaB activation but is not required for ADAP-dependent adhesion. ADAP knockout T cells, NF-kappaB reporter/EMSA, IkappaB phosphorylation/degradation, CARMA1-BCL10-MALT1 co-immunoprecipitation, domain mapping mutants Science High 17478723
2007 RIAM constitutively interacts with SKAP-55 in T cells; the ADAP/SKAP-55 module relocates RIAM and Rap1 to the plasma membrane following TCR activation; SKAP-55/RIAM complex is essential for TCR-mediated adhesion and T cell-APC conjugate formation; RIAM links ADAP/SKAP-55 to active Rap1. Co-immunoprecipitation in transfection system and primary T cells, domain mapping, subcellular fractionation, adhesion and conjugate formation assays Molecular and cellular biology High 17403904
2009 ADAP is an essential component of alphaIIbbeta3-mediated platelet mechanotransduction; ADAP-deficient platelets show defective spreading and F-actin assembly under shear flow (but not static conditions), form unstable thrombi after carotid artery injury, and fail to assemble F-actin-rich structures containing SLP-76 and phospho-Vav1; defect is specific to ADAP and not VASP or SKAP-HOM. ADAP knockout mice, shear flow platelet spreading assay, intravital carotid injury thrombosis model, confocal microscopy of F-actin/SLP-76/Vav1 structures Blood High 19996090
2009 The SLP-76-ADAP module is required for LFA-1-mediated costimulation of IL-2 production, F-actin clustering, cell polarization, and T cell motility; LFA-1 costimulation of IL-2 is completely dependent on SLP-76-ADAP binding (M12 mutant blocks all effects); ADAP expression with LFA-1 ligation alone is sufficient to polarize T cells; LFA-1-ADAP polarization depends on Src kinases, Rho GTPases, PLC, and PI3K. ADAP-/- primary T cells, ADAP mutants (M12), IL-2 production assay, F-actin clustering microscopy, T cell polarization assay, motility assay, pharmacological inhibitors Proceedings of the National Academy of Sciences of the United States of America High 19617540
2010 ADAP requires two distinct sites to activate NF-kappaB in T cells: a CARMA1-binding site critical for IKKgamma ubiquitination, and a TAK1-binding site critical for IKK phosphorylation; ADAP recruits TAK1 and the CBM complex but not IKK to PKCtheta; ADAP is not required for TAK1 activation itself. ADAP domain mutants expressed in ADAP-deficient T cells, co-immunoprecipitation of TAK1/CARMA1/IKK with PKCtheta, IKK phosphorylation/ubiquitination assays The Journal of biological chemistry High 20164171
2010 Quantitative mass spectrometry (SILAC and 18O-labeling) of phosphopeptide pulldowns identified SLP-76, Ras GTPase activating protein, and other TCR proximal complex proteins as phosphorylation-dependent interaction partners of ADAP at Y595, Y625, and Y771; Nck was confirmed as a direct phosphorylation-dependent binding partner of ADAP. Phosphopeptide pulldown, SILAC and 18O quantitative mass spectrometry from Jurkat lysates Journal of proteome research Medium 20568816
2010 ADAP contains multiple phosphotyrosine sites; SLP-76, PLCgamma, PIK3R1, Nck, CRK, Gads, and RasGAP are phospho-dependent binding partners of the central YDDV motif of ADAP; phosphorylation-dependent ADAP–Nck interaction is confirmed by yeast two-hybrid, immunoprecipitation, and pulldown, indicating ADAP directly links integrins to cytoskeletal modulators independently of SLP-76. In vitro phosphorylation/mass spectrometry mapping, Y-to-F mutagenesis, SILAC peptide pulldown, yeast two-hybrid, immunoprecipitation, binary pulldown PloS one High 20661443
2011 The ADAP/SKAP55 module controls CCR7-mediated LFA-1 affinity and avidity regulation; two independent pools of the ADAP/SKAP55 module exist: one interacts with RAPL/Mst1 and another with RIAM/Mst1/Kindlin-3; both pools require ADAP/SKAP55 to bind LFA-1 upon CCR7 stimulation; loss of the module delays lymph node homing and reduces intranodal T cell motility in vivo. ADAP/SKAP55-deficient mice, co-immunoprecipitation of module with RAPL/RIAM complexes, in vivo homing assay, intravital two-photon microscopy, LFA-1 affinity/avidity assay Blood High 22117043
2011 Nck cooperates with ADAP for SLP-76-dependent actin rearrangement; Nck is necessary but insufficient for WASp recruitment; ADAP enables SLP-76-WASp interactions via the SLP-76 SH2 domain binding ADAP; Nck interacts via its SH2 domain with phosphorylated YDDV sites on ADAP. siRNA knockdown of Nck/ADAP, co-immunoprecipitation, actin polymerization assay, WASp recruitment microscopy Molecular and cellular biology High 21536650
2011 Physical association of ADAP with SKAP55 is both necessary and sufficient to rescue integrin function in ADAP-deficient T cells (shown via SKAP-ADAP chimera); SKAP55 pleckstrin homology domain residue R131 is required for ADAP recruitment to LFA-1 and for integrin activation; the SKAP55-PH domain restricts ADAP from associating with the NF-kappaB signalosome. SKAP-ADAP chimeric fusion protein, PH domain point mutant (R131M), ADAP-deficient T cell reconstitution, LFA-1 co-immunoprecipitation, NF-kappaB reporter assay Journal of immunology High 21525391
2012 SLP-76 and ADAP are required for E-selectin-mediated integrin activation and slow leukocyte rolling promoting ischemia-reperfusion-induced AKI in mice; two N-terminal tyrosines and SH2 domain of SLP-76 are required; Bruton tyrosine kinase acts downstream of SLP-76 and together with ADAP regulates PI3Kgamma- and PLCgamma2-dependent integrin affinity and avidity; blocking both pathways abolishes integrin regulation. Genetically engineered mice, transduced Slp76-/- leukocytes, slow rolling assay, pharmacological inhibitors of PI3Kgamma/PLCgamma2, AKI model The Journal of experimental medicine High 22291096
2013 ADAP contains three binding sites for SLP-76 SH2 domain; multipoint binding to ADAP oligomerizes the SLP-76 SH2 domain in vitro; all three binding sites are critical for SLP-76 microcluster assembly but any two sites partially restore microclusters; multipoint ADAP–SLP-76 binding facilitates assembly of SLP-76 microclusters. Biophysical methods (analytical ultracentrifugation, SPR) to characterize SLP-76 SH2–ADAP interactions, confocal imaging of microclusters, ADAP mutants with combinations of binding site mutations Molecular and cellular biology High 23979596
2013 Fyn and ADAP form a complex that exclusively regulates production of inflammatory cytokines (but not cytotoxicity) in NK cells via a Carma1-Bcl-10-MAP3K7 signaling axis. Genetic knockouts (Fyn, ADAP), NK cell cytotoxicity assay, cytokine production measurement, co-immunoprecipitation of Fyn-ADAP complex Nature immunology High 24036998
2014 Nck1 and Nck2 interact with ADAP via their SH2 domains at phosphorylated Y595DDV and Y651DDV sites; endogenous ADAP is phosphorylated at these sites in primary human T cell blasts; ADAP and Nck cooperatively facilitate T cell adhesion to ICAM-1. Co-immunoprecipitation in primary human T cells, SH2 domain specificity assay, adhesion assay to ICAM-1 Molecular immunology Medium 24769494
2014 ADAP promotes activation of integrin alphaIIbbeta3 in platelets through distinct associations with talin and kindlin-3; GST pulldowns identified separate ADAP regions for talin vs. kindlin binding; ADAP-deficient platelets show reduced talin co-localization with alphaIIbbeta3 and reduced irreversible fibrinogen binding; in CHO cells, ADAP enables kindlin-3 to promote agonist-dependent alphaIIbbeta3 activation within an alphaIIbbeta3/talin complex. GST pulldown domain mapping, proximity ligation assay, immunofluorescence co-localization, flow cytometry of integrin activation, reconstitution in CHO cells, ADAP knockout platelets Blood High 24523237
2015 Loss-of-function mutation (c.393G>A nonsense) in the FYB gene causes autosomal recessive small-platelet thrombocytopenia in humans; patient platelets show reduced pseudopodium formation, increased basal P-selectin/PAC-1 expression, and reduced increment of activation markers after ADP stimulation, demonstrating ADAP is required for normal platelet production and function. Homozygosity mapping, exome sequencing, bone marrow morphology, flow cytometry of platelet activation markers, scanning electron microscopy of platelet morphology Journal of thrombosis and haemostasis High 25876182
2015 The ADAP-SKAP55 module reduces CD8+ T cell cytotoxicity and enhances PD-1 expression in a Fyn-, Ca2+-, and NFATc1-dependent manner; knockout of SKAP55 or ADAP reduces PD-1 expression on CD8+ effector cells and enhances anti-tumor immunity in vivo. ADAP/SKAP55 knockout mice, DC vaccine tumor models, adoptive transfer of KO CD8+ T cells, NFATc1 inhibitor (CsA), PD-1 flow cytometry EMBO molecular medicine Medium 25851535
2015 ADAP forms a complex with TRAF6 and TAK1 in CD8+ T cells and activates SMAD3 to increase autocrine TGF-beta1 production; TGF-beta1 induces CD103 expression via an ADAP-, TRAF6-, and SMAD3-dependent pathway, creating a positive feedback loop protecting from influenza virus infection. Co-immunoprecipitation of ADAP-TRAF6-TAK1 complex, SMAD3 phosphorylation assay, ADAP-/- mice CD8+ T cells, TGF-beta1/CD103 expression measurement, influenza infection model PLoS pathogens Medium 25909459
2015 ZAP70 is identified as a novel ADAP interaction partner via its N-terminal SH2 domain binding phosphorylated ADAP-hSH3(N) at pY571; this interaction is inducible by TCR or chemokine stimulation; Y571 of ADAP is required for chemokine-directed T cell migration but not TCR-dependent adhesion or conjugate formation. SILAC interaction proteomics, NMR spectroscopy mapping of ZAP70-SH2–ADAP interaction, microscale thermophoresis (Kd = 2.3 µM), Y571F mutant functional assay (adhesion, migration) Molecular & cellular proteomics High 26246585
2017 Ubc9 (SUMO E2 conjugase) directly interacts with ADAP in vitro and in vivo via ADAP residues 674-700 (nuclear localization sequence); this interaction increases upon anti-CD3 stimulation; knockdown of Ubc9 or expression of Ubc9-binding-deficient ADAP mutant decreases TCR-induced integrin adhesion, LFA-1 clustering, and membrane recruitment of Rap1/RapL and Rac1 activation, without affecting TCR proximal signaling. Co-immunoprecipitation in vitro and in vivo, domain mapping, shRNA knockdown, Rac1 GTPase activity assay, Rap1/RapL subcellular fractionation, integrin adhesion/clustering assays Journal of immunology Medium 29127148
2018 ADAP is an upstream regulator that pre-positions at TCR contact sites before SLP-76; pY595 is essential for normal ADAP function and virtually all ADAP phosphorylation is restricted to the pY595 pool; multivalent SLP-76 SH2–ADAP interactions are required to sustain ADAP phosphorylation; non-phosphorylated ADAP enriches in actin-rich protrusive structures and promotes retention/assembly of nascent SLP-76 oligomers into persistent microclusters. Live-cell imaging with phospho-specific anti-pY595 antibody, point mutants of ADAP, SLP-76 microcluster analysis, integrin-independent adhesion assay, CD69 upregulation assay Journal of cell science High 30305305
2018 ADAP deficiency in megakaryocytes causes microthrombocytopenia due to impaired MK polarization and ectopic release of (pro)platelet-like particles into the bone marrow compartment; ADAP-deficient MKs show reduced spreading on extracellular matrix, impaired podosome formation, defective polarization of the demarcation membrane system, and reduced beta1 integrin activation. Constitutive and MK-specific (PF4-Cre) ADAP knockout mice, 3D confocal whole-sternum imaging, intravital 2-photon microscopy, cultured MK spreading/podosome assay, beta1 integrin activation flow cytometry Blood High 29950291
2021 ADAP phosphorylation at Y571 is required to prime STAT3 for activation in TLR4-stimulated macrophages; ADAP interacts with STAT3 and loss of ADAP reduces LPS-mediated STAT3 phosphorylation and enhances M1 macrophage polarization; Y571F mutation severely impairs ADAP's ability to stimulate STAT3 activity. ADAP-/- macrophages, Y571F point mutant, co-immunoprecipitation of ADAP-STAT3, STAT3 phosphorylation assay, cytokine profiling, macrophage polarization assay Journal of immunology Medium 33431658
2022 ADAP restrains platelet phagocytosis by macrophages in ITP by competing with STAT1 for binding to importin alpha5; ADAP deficiency potentiates STAT1 nuclear entry, selectively enhancing FcgammaRI/IV transcription; pharmacological inhibition of STAT1 or disruption of STAT1-importin alpha5 interaction relieves thrombocytopenia in ADAP-deficient mice. Adap-/- mice, co-immunoprecipitation of ADAP-STAT1-importin alpha5, competition binding assay, FcgammaR transcription measurement, macrophage phagocytosis assay, pharmacological rescue Cellular & molecular immunology Medium 35637282
2024 ADAP selectively interacts with RIG-I (but not MDA5) and cooperates with it to activate IFN-beta transcription; ADAP deficiency increases ISGylation of RIG-I, whereas ADAP overexpression decreases RIG-I ISGylation; loss of ADAP impairs IRF3/TBK1 phosphorylation and increases RNA virus replication in macrophages. Co-immunoprecipitation (ADAP-RIG-I), ISGylation assay, IRF3/TBK1 phosphorylation measurement, ADAP-/- macrophages and mice, siRNA knockdown, IFN-beta reporter assay PLoS pathogens Medium 38776321
2025 BTK-mediated tyrosine phosphorylation of ADAP at Y571 cooperates with mTOR to converge on STAT3 activation for transactivation of the podoplanin (PDPN) promoter in TLR4-stimulated macrophages; ADAP deficiency prevents PDPN upregulation and blocks generation of a PDPNhi M2-like peritoneal macrophage subset that is protective in sepsis. ADAP-/- mice, BTK inhibition, mTOR inhibition, STAT3 activation assay, PDPN promoter reporter, peritoneal macrophage subset flow cytometry, sepsis model JCI insight Medium 39903516

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Coupling of the TCR to integrin activation by Slap-130/Fyb. Science (New York, N.Y.) 250 11567141
2000 Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins and the Arp2/3 complex link T cell receptor (TCR) signaling to the actin cytoskeleton. The Journal of cell biology 246 10747096
1997 Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-containing leukocyte protein 76 and modulates interleukin 2 production. Proceedings of the National Academy of Sciences of the United States of America 236 9207119
2001 Positive regulation of T cell activation and integrin adhesion by the adapter Fyb/Slap. Science (New York, N.Y.) 228 11567140
1997 Molecular cloning of SLAP-130, an SLP-76-associated substrate of the T cell antigen receptor-stimulated protein tyrosine kinases. The Journal of biological chemistry 213 9115214
2001 Evidence for a molecular complex consisting of Fyb/SLAP, SLP-76, Nck, VASP and WASP that links the actin cytoskeleton to Fcgamma receptor signalling during phagocytosis. Journal of cell science 164 11739662
1995 Mutations in the erythrocyte chemokine receptor (Duffy) gene: the molecular basis of the Fya/Fyb antigens and identification of a deletion in the Duffy gene of an apparently healthy individual with the Fy(a-b-) phenotype. British journal of haematology 118 7669660
1998 FYB (FYN binding protein) serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells. Proceedings of the National Academy of Sciences of the United States of America 117 9671755
1995 Molecular basis and PCR-DNA typing of the Fya/fyb blood group polymorphism. Human genetics 108 7705836
2006 The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1. Molecular and cellular biology 104 16980616
1995 Genomic organization of the glycoprotein D gene: Duffy blood group Fya/Fyb alloantigen system is associated with a polymorphism at the 44-amino acid residue. Blood 97 7833467
2007 RIAM links the ADAP/SKAP-55 signaling module to Rap1, facilitating T-cell-receptor-mediated integrin activation. Molecular and cellular biology 96 17403904
2005 Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76-ADAP. The EMBO journal 95 15933714
2012 Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury. The Journal of experimental medicine 92 22291096
1999 FYN-T-FYB-SLP-76 interactions define a T-cell receptor zeta/CD3-mediated tyrosine phosphorylation pathway that up-regulates interleukin 2 transcription in T-cells. The Journal of biological chemistry 88 10409671
1998 The Gcn4p activation domain interacts specifically in vitro with RNA polymerase II holoenzyme, TFIID, and the Adap-Gcn5p coactivator complex. Molecular and cellular biology 85 9488488
1998 Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130. The Journal of biological chemistry 83 9748251
2008 SKAP-55, SKAP-55-related and ADAP adaptors modulate integrin-mediated immune-cell adhesion. Trends in cell biology 80 18760924
2007 Regulation of NF-kappaB activation in T cells via association of the adapter proteins ADAP and CARMA1. Science (New York, N.Y.) 79 17478723
2004 ADAP-SLP-76 binding differentially regulates supramolecular activation cluster (SMAC) formation relative to T cell-APC conjugation. The Journal of experimental medicine 77 15477347
2013 Signaling by Fyn-ADAP via the Carma1-Bcl-10-MAP3K7 signalosome exclusively regulates inflammatory cytokine production in NK cells. Nature immunology 75 24036998
1998 The Fy(x) phenotype is associated with a missense mutation in the Fy(b) allele predicting Arg89Cys in the Duffy glycoprotein. British journal of haematology 74 9886340
2009 SLP-76-ADAP adaptor module regulates LFA-1 mediated costimulation and T cell motility. Proceedings of the National Academy of Sciences of the United States of America 67 19617540
1999 Novel isoform of lymphoid adaptor FYN-T-binding protein (FYB-130) interacts with SLP-76 and up-regulates interleukin 2 production. The Journal of biological chemistry 64 10497204
2011 CCR7-mediated LFA-1 functions in T cells are regulated by 2 independent ADAP/SKAP55 modules. Blood 63 22117043
1999 Cutting edge: SLP-76 cooperativity with FYB/FYN-T in the Up-regulation of TCR-driven IL-2 transcription requires SLP-76 binding to FYB at Tyr595 and Tyr651. Journal of immunology (Baltimore, Md. : 1950) 63 10570256
2016 Ultrasensitive Antibody Detection by Agglutination-PCR (ADAP). ACS central science 60 27064772
2001 Adaptor FYB (Fyn-binding protein) regulates integrin-mediated adhesion and mediator release: differential involvement of the FYB SH3 domain. Proceedings of the National Academy of Sciences of the United States of America 60 11553777
2000 Cutting edge: a novel function for the SLAP-130/FYB adapter protein in beta 1 integrin signaling and T lymphocyte migration. Journal of immunology (Baltimore, Md. : 1950) 60 10640723
2010 Identification of phosphorylation-dependent interaction partners of the adapter protein ADAP using quantitative mass spectrometry: SILAC vs (18)O-labeling. Journal of proteome research 57 20568816
2002 Communication between the TCR and integrins: role of the molecular adapter ADAP/Fyb/Slap. Current opinion in immunology 56 11973129
2014 ADAP interactions with talin and kindlin promote platelet integrin αIIbβ3 activation and stable fibrinogen binding. Blood 55 24523237
2000 Functional association between SLAP-130 and SLP-76 in Jurkat T cells. The Journal of biological chemistry 52 10671560
2015 ADAP and SKAP55 deficiency suppresses PD-1 expression in CD8+ cytotoxic T lymphocytes for enhanced anti-tumor immunotherapy. EMBO molecular medicine 51 25851535
2011 Functional cooperation between the proteins Nck and ADAP is fundamental for actin reorganization. Molecular and cellular biology 51 21536650
2006 ADAP is required for normal alphaIIbbeta3 activation by VWF/GP Ib-IX-V and other agonists. Blood 50 17003372
2005 Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells. The Journal of biological chemistry 46 15849195
2003 Interaction between the Yersinia protein tyrosine phosphatase YopH and eukaryotic Cas/Fyb is an important virulence mechanism. Cellular microbiology 46 12542470
2015 Deleterious mutation in the FYB gene is associated with congenital autosomal recessive small-platelet thrombocytopenia. Journal of thrombosis and haemostasis : JTH 43 25876182
1987 The mouse homolog of the human amyloid beta protein (AD-AP) gene is located on the distal end of mouse chromosome 16: further extension of the homology between human chromosome 21 and mouse chromosome 16. Biochemical and biophysical research communications 42 3555492
2013 Multipoint binding of the SLP-76 SH2 domain to ADAP is critical for oligomerization of SLP-76 signaling complexes in stimulated T cells. Molecular and cellular biology 41 23979596
2018 Antibody detection by agglutination-PCR (ADAP) enables early diagnosis of HIV infection by oral fluid analysis. Proceedings of the National Academy of Sciences of the United States of America 37 29358368
2010 Adhesion and degranulation promoting adapter protein (ADAP) is a central hub for phosphotyrosine-mediated interactions in T cells. PloS one 34 20661443
2005 The helically extended SH3 domain of the T cell adaptor protein ADAP is a novel lipid interaction domain. Journal of molecular biology 33 15843031
1987 The beta amyloid protein (AD-AP) cDNA hybridizes in normal and Alzheimer individuals near the interface of 21q21 and q22.1. Annales de genetique 33 3314665
2018 ADAP deficiency impairs megakaryocyte polarization with ectopic proplatelet release and causes microthrombocytopenia. Blood 32 29950291
2010 NF-kappaB activation in T cells requires discrete control of IkappaB kinase alpha/beta (IKKalpha/beta) phosphorylation and IKKgamma ubiquitination by the ADAP adapter protein. The Journal of biological chemistry 31 20164171
2009 Role for ADAP in shear flow-induced platelet mechanotransduction. Blood 31 19996090
1980 Quantitative immunoferritin microscopy of Fya, Fyb, Jka, U, and Dib antigen site numbers on human red cells. Blood 31 6777001
2007 Adhesion and degranulation-promoting adapter protein (ADAP) positively regulates T cell sensitivity to antigen and T cell survival. Journal of immunology (Baltimore, Md. : 1950) 29 17785790
2021 The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events. Frontiers in immunology 26 34295339
2006 ADAP is dispensable for NK cell development and function. International immunology 26 16775024
2015 The Fyn-ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells. Frontiers in immunology 25 26441977
2008 Distinct regulation of integrin-dependent T cell conjugate formation and NF-kappa B activation by the adapter protein ADAP. Journal of immunology (Baltimore, Md. : 1950) 24 18802088
2006 The production of red blood cell alloantibodies in mice transfused with blood from transgenic Fyb-expressing mice. Transfusion 24 17002623
2004 Structure of a helically extended SH3 domain of the T cell adapter protein ADAP. Structure (London, England : 1993) 23 15062083
2015 Discrimination between 8-oxo-2'-deoxyguanosine and 2'-deoxyguanosine in DNA by the single nucleotide primer extension reaction with adap triphosphate. Angewandte Chemie (International ed. in English) 22 25727406
1997 Comparison of Fy(b) status as determined serologically and genetically. Transfusion medicine (Oxford, England) 22 9195700
2010 HPK1 competes with ADAP for SLP-76 binding and via Rap1 negatively affects T-cell adhesion. European journal of immunology 20 20957749
2003 Targeting of MIST to Src-family kinases via SKAP55-SLAP-130 adaptor complex in mast cells. FEBS letters 20 12681493
2022 ADAP restraint of STAT1 signaling regulates macrophage phagocytosis in immune thrombocytopenia. Cellular & molecular immunology 19 35637282
2018 ADAP is an upstream regulator that precedes SLP-76 at sites of TCR engagement and stabilizes signaling microclusters. Journal of cell science 19 30305305
2016 ADAP plays a pivotal role in CD4+ T cell activation but is only marginally involved in CD8+ T cell activation, differentiation, and immunity to pathogens. Journal of leukocyte biology 18 27605210
2014 Recessive thrombocytopenia likely due to a homozygous pathogenic variant in the FYB gene: case report. BMC medical genetics 18 25516138
2011 The pleckstrin homology domain in the SKAP55 adapter protein defines the ability of the adapter protein ADAP to regulate integrin function and NF-kappaB activation. Journal of immunology (Baltimore, Md. : 1950) 18 21525391
2009 The brain-specific protein, p42(IP4) (ADAP 1) is localized in mitochondria and involved in regulation of mitochondrial Ca2+. Journal of neurochemistry 17 19383085
2015 The Immune Adaptor ADAP Regulates Reciprocal TGF-β1-Integrin Crosstalk to Protect from Influenza Virus Infection. PLoS pathogens 16 25909459
2008 Defective positive selection results in T cell lymphopenia and increased autoimmune diabetes in ADAP-deficient BDC2.5-C57BL/6 mice. European journal of immunology 16 18383041
2005 Fyn binding protein, Fyb, interacts with mammalian actin binding protein, mAbp1. FEBS letters 15 15848169
2001 Adaptor ADAP (adhesion- and degranulation-promoting adaptor protein) regulates beta1 integrin clustering on mast cells. Biochemical and biophysical research communications 15 11741310
2014 A novel FY*A allele with the 265T and 298A SNPs formerly associated exclusively with the FY*B allele and weak Fy(b) antigen expression: implication for genotyping interpretative algorithms. Vox sanguinis 14 25092430
2013 T cell-independent modulation of experimental autoimmune encephalomyelitis in ADAP-deficient mice. Journal of immunology (Baltimore, Md. : 1950) 14 24101551
2011 OFF-to-ON type fluorescent probe for the detection of 8-oxo-dG in DNA by the Adap-masked ODN probe. Bioorganic & medicinal chemistry letters 14 22119473
2023 Super Enhancer Regulatory Gene FYB1 Promotes the Progression of T Cell Acute Lymphoblastic Leukemia by Activating IGLL1. Journal of immunology research 13 37767202
2012 ADAP regulates cell cycle progression of T cells via control of cyclin E and Cdk2 expression through two distinct CARMA1-dependent signaling pathways. Molecular and cellular biology 13 22411628
2005 Physical and functional association of c-Src and adhesion and degranulation promoting adaptor protein (ADAP) in osteoclastogenesis in vitro. The Journal of biological chemistry 13 16020549
2014 The adapter proteins ADAP and Nck cooperate in T cell adhesion. Molecular immunology 12 24769494
2013 Multistage T cell-dendritic cell interactions control optimal CD4 T cell activation through the ADAP-SKAP55-signaling module. Journal of immunology (Baltimore, Md. : 1950) 12 23918975
2007 Inactivation of T-cell receptor-mediated integrin activation prolongs allograft survival in ADAP-deficient mice. Transplantation 12 17700167
2005 Interaction between the Yersinia tyrosine phosphatase YopH and its macrophage substrate, Fyn-binding protein, Fyb. Journal of molecular microbiology and biotechnology 12 16415594
2002 ADAP-ting TCR signaling to integrins. Science's STKE : signal transduction knowledge environment 11 11943877
2021 ADAP Y571 Phosphorylation Is Required to Prime STAT3 for Activation in TLR4-Stimulated Macrophages. Journal of immunology (Baltimore, Md. : 1950) 10 33431658
2014 2,6-diaminopurine nucleoside derivative of 9-ethyloxy-2-oxo-1,3-diazaphenoxazine (2-amino-Adap) for recognition of 8-oxo-dG in DNA. Bioorganic & medicinal chemistry 10 24530029
2013 FYB gene polymorphisms are associated with susceptibility for systemic lupus erythemathosus (SLE). Human immunology 10 23628395
2013 Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors. Retrovirology 10 24047317
2011 TM4SF10 and ADAP interaction in podocytes: role in Fyn activity and nephrin phosphorylation. American journal of physiology. Cell physiology 10 21881001
2015 Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1. Molecular biology of the cell 9 26202465
2020 ADAP Promotes Degranulation and Migration of NK Cells Primed During in vivo Listeria monocytogenes Infection in Mice. Frontiers in immunology 8 32038647
2019 Characterization of Mice with a Platelet-Specific Deletion of the Adapter Molecule ADAP. Molecular and cellular biology 8 30833485
2012 The adapter protein ADAP is required for selected dendritic cell functions. Cell communication and signaling : CCS 8 22672517
2009 ADAP deficiency combined with costimulation blockade synergistically protects intestinal allografts. Transplant international : official journal of the European Society for Organ Transplantation 8 19678902
2025 Molecular control of PDPNhi macrophage subset induction by ADAP as a host defense in sepsis. JCI insight 7 39903516
2019 Immune Cell-Type Specific Ablation of Adapter Protein ADAP Differentially Modulates EAE. Frontiers in immunology 7 31632410
2015 Analysis of Phosphorylation-dependent Protein Interactions of Adhesion and Degranulation Promoting Adaptor Protein (ADAP) Reveals Novel Interaction Partners Required for Chemokine-directed T cell Migration. Molecular & cellular proteomics : MCP 7 26246585
1984 Red-cell auto-antibodies mimicking anti-Fyb specificity. Vox sanguinis 7 6741036
2017 Ubc9 Binds to ADAP and Is Required for Rap1 Membrane Recruitment, Rac1 Activation, and Integrin-Mediated T Cell Adhesion. Journal of immunology (Baltimore, Md. : 1950) 6 29127148
2024 Dampening of ISGylation of RIG-I by ADAP regulates type I interferon response of macrophages to RNA virus infection. PLoS pathogens 5 38776321
2021 Assessment of calciprotein particle formation by AUC of the absorbance change: effect of FYB-931, a novel bisphosphonate compound. The Journal of pharmacy and pharmacology 5 33882129
2016 Integrin Activation Through the Hematopoietic Adapter Molecule ADAP Regulates Dendritic Development of Hippocampal Neurons. Frontiers in molecular neuroscience 5 27746719
2007 Biological properties of 4-methyl-2,7-diamino-5,10-diphenyl-4,9-diazapyrenium hydrogensulfate (ADAP). Cancer chemotherapy and pharmacology 5 18034344