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Showing FYB1 — FYB is a alias.

FYB1

FYN-binding protein 1 · UniProt O15117

Length
783 aa
Mass
85.4 kDa
Annotated
2026-06-09
100 papers in source corpus 51 papers cited in narrative 51 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FYB1 (FYB/ADAP/SLAP-130) is a hematopoietic-specific cytosolic scaffold adapter that couples antigen- and immune-receptor signaling to integrin activation, actin remodeling, and transcriptional programs (PMID:9207119, PMID:11567141). It is selectively phosphorylated by the Src kinase FYN-T, principally at Y595 (with Y651), generating docking sites that are bound by the SLP-76 SH2 domain and by Nck; multipoint binding to three SLP-76 sites oligomerizes SLP-76 and is required for SLP-76 microcluster assembly at the immunological synapse (PMID:10409671, PMID:10570256, PMID:23979596, PMID:20661443). Through its proline-rich region, ADAP constitutively engages the SH3 domain of SKAP55, protecting SKAP55 from proteolysis, and this ADAP/SKAP55 module targets active Rap1 and RIAM to the plasma membrane to drive inside-out activation and clustering of LFA-1, a function genetically dissociable from TCR-induced actin polymerization (PMID:11567141, PMID:15849195, PMID:16980616, PMID:17403904). A spatially and functionally distinct pool of ADAP coordinates NF-κB activation by recruiting CARMA1 and TAK1 to control IKK phosphorylation and IKKγ ubiquitination, with the integrin-regulatory and NF-κB-regulatory functions assigned to mutually exclusive ADAP pools (PMID:17478723, PMID:21525391, PMID:20164171). ADAP additionally links SLP-76 to the Ena/VASP–WASP–Arp2/3 actin machinery to drive actin rearrangement during T cell synapse formation and FcR-mediated phagocytosis (PMID:10747096, PMID:11739662, PMID:21536650), and in platelets and megakaryocytes it associates with talin and kindlin-3 to support αIIbβ3 activation and proper proplatelet release (PMID:17003372, PMID:24523237, PMID:29950291). In macrophages, ADAP governs transcriptional outputs by competing with STAT1 for importin α5 to limit STAT1 nuclear entry, by coactivating STAT3, by restraining RIG-I ISGylation to sustain type I interferon responses, and by driving TLR4-induced podoplanin expression through a BTK–Y571–mTOR–STAT3 axis (PMID:33431658, PMID:35637282, PMID:38776321, PMID:39903516).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1997 High

    Established FYB1 as a FYN- and SLP-76-associated phosphoprotein in T cells, defining it as a candidate TCR signaling adapter and raising the question of whether it positively or negatively tunes activation.

    Evidence cDNA cloning, reciprocal co-IP mapping binding to the SLP-76 SH2 domain, and IL-2 reporter/secretion assays in T cell lines

    PMID:9115214 PMID:9207119

    Open questions at the time
    • Opposite functional readouts (augmented vs. diminished IL-2) left its regulatory sign ambiguous
    • No phosphosites mapped
    • Endogenous loss-of-function not yet tested
  2. 1998 High

    Identified SKAP55 as a constitutive SH3-domain partner of the ADAP proline-rich region, defining the core ADAP/SKAP55 module.

    Evidence Yeast two-hybrid, co-IP, truncation/point mutant co-transfection in COS cells, and confocal colocalization

    PMID:9671755 PMID:9748251

    Open questions at the time
    • Functional consequence of the ADAP–SKAP55 interaction not yet established
    • Downstream effectors of the module unknown
  3. 1999 High

    Resolved the FYN-T–ADAP–SLP-76 signaling matrix and mapped the phosphotyrosines (Y595, Y651) that create SLP-76 SH2 docking sites, defining the molecular basis of receptor coupling.

    Evidence In vitro kinase assays, Y→F mutagenesis, co-IP in Jurkat cells, and IL-2/NF-AT reporter assays

    PMID:10409671 PMID:10497204 PMID:10570256

    Open questions at the time
    • Whether synergy required FYN–ADAP binding was dispensable, narrowing function to the SLP-76 arm
    • Physiological phenotype still inferred from overexpression
  4. 2000 High

    Connected ADAP to actin polymerization and integrin signaling, linking the SLP-76 complex to the Ena/VASP–WASP–Arp2/3 machinery and to β1 integrin-driven migration.

    Evidence EVH1 pulldown, co-IP of a SLAP/SLP-76/Nck/VASP/WASP complex, inhibitory peptide competition, and transwell migration assays

    PMID:10640723 PMID:10671560 PMID:10747096

    Open questions at the time
    • Relationship between actin and integrin outputs not yet separated genetically
    • Mechanism of integrin avidity change undefined
  5. 2001 High

    Knockout mice resolved the central question of ADAP function, showing it specifically couples TCR signaling to integrin (LFA-1) clustering and adhesion while being dispensable for TCR-induced actin polymerization.

    Evidence Two independent Fyb/Slap KO mouse lines with proliferation, cytokine, integrin clustering/adhesion, and F-actin assays; parallel FcR studies in mast cells and macrophages

    PMID:11553777 PMID:11567140 PMID:11567141 PMID:11739662 PMID:11741310

    Open questions at the time
    • Molecular link from ADAP to integrin avidity not yet identified
    • Cross-cell-type generalization (mast cell, macrophage) still descriptive
  6. 2004 High

    Defined the unusual C-terminal architecture of ADAP and dissected the SLP-76-binding YDDV motifs as differential controllers of synapse organization.

    Evidence NMR structure of the helically-extended SH3 (hSH3) fold and YDDV→FDDF (M12) mutagenesis with SMAC imaging and conjugation/IL-2 assays

    PMID:15062083 PMID:15477347

    Open questions at the time
    • Ligand of the hSH3 fold unknown at this stage
    • pSMAC vs conjugation outputs molecularly unexplained
  7. 2005 High

    Assigned the hSH3 domain a lipid-binding function and showed ADAP stabilizes SKAP55 against proteolysis, explaining the obligate nature of the module.

    Evidence Liposome co-sedimentation and NMR mapping of PIP2/PIP3 binding; pulse-chase protein stability assays with SH3 domain mutants

    PMID:15843031 PMID:15848169 PMID:15849195 PMID:15933714 PMID:16020549

    Open questions at the time
    • In vivo relevance of hSH3 lipid binding to membrane targeting not directly tested
    • Redox (SHP-2) and osteoclast/mAbp1 links from single labs
  8. 2007 High

    Resolved how the ADAP/SKAP55 module drives inside-out integrin activation, by targeting active Rap1 and RIAM to the plasma membrane without altering Rap1 GTPase activity.

    Evidence Module-disruption mutants, Rap1 membrane fractionation and GTPase assays, RIAM/SKAP55 domain mapping, and gain-of-function membrane targeting in T cells

    PMID:16980616 PMID:17403904

    Open questions at the time
    • How the module is itself recruited to the membrane not yet defined
    • Step coupling Rap1/RIAM to LFA-1 conformational change unresolved
  9. 2007 High

    Separated ADAP's NF-κB function from its adhesion function, identifying a CARMA1-binding region required for CBM complex assembly and IKK activation.

    Evidence ADAP-/- T cells, CARMA1 co-IP, EMSA, IκB degradation assays, and domain mutagenesis distinguishing adhesion vs NF-κB regions

    PMID:17478723 PMID:20164171

    Open questions at the time
    • Whether the two functions use physically distinct ADAP pools not yet shown
    • TAK1 vs CARMA1 division of labor refined in subsequent work
  10. 2010 High

    Characterized ADAP as a multivalent phosphotyrosine interaction hub that oligomerizes SLP-76 to nucleate signaling microclusters, and mapped its quantitative interactome.

    Evidence AUC/SPR biophysics of SLP-76 SH2 oligomerization, SILAC/18O phosphopeptide-pulldown mass spectrometry, and confocal microcluster imaging

    PMID:20568816 PMID:20661443 PMID:20957749 PMID:21536650 PMID:23979596

    Open questions at the time
    • Functional weight of individual MS-identified partners (RasGAP, PLCγ, PIK3R1) not individually validated
    • Stoichiometry in vivo not determined
  11. 2011 High

    Demonstrated that integrin- and NF-κB-regulating ADAP pools are mutually exclusive and that SKAP55's PH domain (R131) recruits ADAP to the LFA-1 complex, mechanistically separating the two outputs.

    Evidence SKAP-ADAP chimera and R131M PH-domain point mutant rescue/block of integrin vs NF-κB in ADAP-/- T cells, plus LFA-1 costimulation assays

    PMID:19617540 PMID:21525391

    Open questions at the time
    • Structural basis of PH-domain membrane/LFA-1 engagement not solved
    • Switch that partitions ADAP between pools unknown
  12. 2012 High

    Extended ADAP signaling to cell-cycle progression and to neutrophil rolling, showing its NF-κB/JNK arm drives Cdk2/cyclin E and its adhesion arm supports selectin-triggered integrin activation in vivo.

    Evidence ADAP domain mutants with cell-cycle and cyclin E ubiquitination assays; ADAP-/-/SLP-76-/- mice with intravital leukocyte rolling and integrin affinity/avidity measurements

    PMID:22291096 PMID:22411628

    Open questions at the time
    • Direct ADAP target controlling cyclin E turnover not identified
    • BTK–ADAP relationship in neutrophils mechanistically incomplete
  13. 2013 High

    Showed ADAP functions are receptor- and output-selective, with a Fyn–ADAP–CARMA1–BCL10–MAP3K7 axis controlling NK cytokine production but not cytotoxicity.

    Evidence ADAP-/- mice with separated NK cytotoxicity and cytokine assays, Fyn-ADAP co-IP, and pathway-dissecting inhibitors

    PMID:24036998

    Open questions at the time
    • Why cytotoxicity is ADAP-independent at the molecular level not explained
  14. 2014 High

    Identified direct ADAP associations with talin and kindlin-3 in platelets, providing the molecular link from ADAP to αIIbβ3 integrin activation.

    Evidence GST pulldown domain mapping, platelet co-IP/proximity ligation, ADAP-/- mice, and CHO-cell reconstitution of αIIbβ3/talin/kindlin-3

    PMID:17003372 PMID:19996090 PMID:24523237

    Open questions at the time
    • Whether talin/kindlin binding is direct or scaffolded not fully resolved
    • Spatial coordination with Rap1/RIAM in platelets undefined
  15. 2015 High

    Established new phospho-dependent ADAP interactions (ZAP70 at pY571) and tied the module to immune-effector transcription (NFATc1/PD-1, TRAF6/SMAD3/CD103).

    Evidence NMR mapping and microscale thermophoresis (ZAP70-pY571 Kd), Y571F migration assays, and ADAP-/-/SKAP55-/- mice with PD-1, TGF-β1, and CD103 readouts plus tumor and influenza models

    PMID:25851535 PMID:25909459 PMID:26246585

    Open questions at the time
    • How distinct phosphosites (Y571 vs Y595) are differentially used not fully defined
    • Direct transcriptional mechanism downstream of the module incomplete
  16. 2018 High

    Refined the phospho-regulatory model, showing virtually all ADAP tyrosine phosphorylation is restricted to Y595 and that ADAP acts upstream of SLP-76 microcluster formation; megakaryocyte-intrinsic ADAP loss causes microthrombocytopenia.

    Evidence TIRF live imaging with a novel pY595-specific antibody and Y595F mutants; constitutive and PF4-Cre conditional ADAP KO mice with 3D bone marrow imaging and MK spreading/podosome assays

    PMID:29950291 PMID:30305305

    Open questions at the time
    • Reconciliation of Y595-dominance with earlier multi-site MS data not fully addressed
    • Megakaryocyte signaling pathway to proplatelet polarization incomplete
  17. 2022 High

    Revealed a non-canonical nuclear-transport-regulating function of ADAP in macrophages, competing with STAT1 for importin α5 and coactivating STAT3.

    Evidence ADAP-/- macrophages, co-IP/competition assays, nuclear fractionation, FcγR transcription analysis, and Y571F STAT3 coactivation assays

    PMID:33431658 PMID:35637282

    Open questions at the time
    • Whether STAT competition occurs in T cells/platelets not tested
    • Direct ADAP–importin α5 binding interface not mapped
  18. 2025 High

    Expanded ADAP into innate antiviral and inflammatory transcription, restraining RIG-I ISGylation to sustain IFN-β and driving TLR4-induced podoplanin via a BTK–Y571–mTOR–STAT3 axis.

    Evidence ADAP-RIG-I co-IP and ISGylation assays with ADAP-/- mice and RNA virus infection; ADAP-/- macrophages with BTK/mTOR inhibitors, Y571 mutagenesis, PDPN promoter assays, and a sepsis model

    PMID:38776321 PMID:39903516

    Open questions at the time
    • Mechanism by which ADAP inhibits RIG-I ISG15 conjugation not defined
    • Whether innate functions require the SKAP55/integrin module unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single scaffold partitions between its mutually exclusive integrin-regulatory, NF-κB, actin, and nuclear-transport/transcriptional pools, and what structural switches dictate phosphosite selection across cell types.
  • No integrated structural model of full-length ADAP in its complexes
  • Switch governing Y571 vs Y595 usage across T cells, platelets, macrophages undefined
  • Quantitative partitioning between integrin, NF-κB, and nuclear pools unmeasured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0008289 lipid binding 1
Localization
GO:0005829 cytosol 3 GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-109582 Hemostasis 4 R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 1
Partners
CARMA1FYNNCKRIAMSKAP55SLP-76TAK1TALIN
Complex memberships
ADAP/SKAP55 moduleCARMA1-BCL10-MALT1 (CBM) complexSLP-76 microcluster/signalosome

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 FYB (FYN binding protein/p120/130) was cloned and shown to associate with the Src kinase p59(fyn) and with SLP-76 via the SLP-76 SH2 domain; it becomes tyrosine-phosphorylated upon TCR/CD3 ligation. Overexpression of FYB augmented IL-2 secretion from a T cell hybridoma in response to TCR ligation. cDNA cloning, co-immunoprecipitation, overexpression in T cell hybridoma Proceedings of the National Academy of Sciences of the United States of America High 9207119
1997 SLAP-130 (FYB1) was cloned as a hematopoietic-specific SLP-76-associated phosphoprotein that is a substrate of TCR-induced protein tyrosine kinases; its SH2 domain-mediated association with SLP-76 was demonstrated, and overexpression of SLAP-130 diminished TCR-induced IL-2 promoter activity and interfered with SLP-76-mediated augmentation, suggesting it acts as a negative regulator. Molecular cloning, co-immunoprecipitation (SH2 domain interaction), overexpression in Jurkat T cells with IL-2 promoter reporter assay The Journal of biological chemistry High 9115214
1998 FYB binds SKAP55 and the related SKAP55R protein through their SH3 domains (interaction with proline-rich sequences of FYB), identified by yeast two-hybrid screen and confirmed by co-immunoprecipitation; FYB and SKAP55 colocalize in the perinuclear region. Both SKAP55 and SKAP55R serve as substrates for FYN kinase. Yeast two-hybrid screen, co-immunoprecipitation, confocal immunofluorescence microscopy, in vitro kinase assay Proceedings of the National Academy of Sciences of the United States of America High 9671755
1998 SLAP-130 (FYB1) is a component of the Fyn complex in human T cells and co-precipitates with SKAP55. The direct association between SLAP-130 and SKAP55 involves the SH3 domain of SKAP55 and the proline-rich sequence of SLAP-130, established by co-transfection of truncation/point mutants in COS cells and yeast two-hybrid. Co-immunoprecipitation from T cells, co-transfection with truncation mutants in COS cells, yeast two-hybrid The Journal of biological chemistry High 9748251
1999 FYN-T selectively phosphorylates FYB, creating a template for recruitment of FYN-T and SLP-76 SH2 domains. Co-expression of FYN-T, FYB, and SLP-76 synergistically up-regulates TCR-driven IL-2 transcription, defining a FYN-T–FYB–SLP-76 signaling matrix. In vitro kinase assay, co-immunoprecipitation, overexpression in T cell lines with IL-2 reporter assay The Journal of biological chemistry High 10409671
1999 FYB-130 is an alternatively spliced isoform of FYB with a 46-amino-acid insertion near the C-terminus; both FYB-120 and FYB-130 bind SLP-76 SH2 and FYN-T SH2 domains and are phosphorylated by FYN-T. FYB-130 caused a significant increase in TCR-driven NF-AT transcription when co-expressed with FYN-T and SLP-76. cDNA cloning, co-immunoprecipitation, overexpression with NF-AT reporter assay, FISH chromosomal mapping The Journal of biological chemistry Medium 10497204
1999 Tyr595 and Tyr651 of FYB are major phosphorylation sites for FYN-T and mediate binding to the SLP-76 SH2 domain in Jurkat T cells. The synergistic up-regulation of IL-2 promoter activity in the FYN-T–FYB–SLP-76 pathway requires the FYB–SLP-76 interaction (at these tyrosines) but not the FYB–FYN-T interaction. Site-directed mutagenesis (Y→F), co-immunoprecipitation in Jurkat T cells, IL-2 promoter reporter assay Journal of immunology High 10570256
2000 FYB/SLAP was identified as a ligand for Ena/VASP EVH1 domains. Upon TCR engagement, FYB/SLAP localizes at the T cell–APC interface and associates with Ena/VASP family proteins, WASP, Nck, and SLP-76 in a complex. Inhibition of FYB/SLAP–Ena/VASP binding or WASP–Arp2/3 interaction impairs TCR-dependent actin rearrangement. Pulldown assay (EVH1 domain), co-immunoprecipitation, confocal microscopy (localization at T cell–bead interface), inhibitory peptide competition The Journal of cell biology High 10747096
2000 SLAP-130/FYB undergoes rapid tyrosine phosphorylation upon α4β1 integrin stimulation and the phosphorylated form associates with the SH2 domain of p59fyn. Overexpression of SLAP-130/FYB in normal T cells enhances migration through fibronectin-coated filters in response to SDF-1α, identifying a role in β1 integrin signaling and T cell motility. Phosphorylation assay, co-immunoprecipitation, overexpression in primary T cells with transwell migration assay Journal of immunology Medium 10640723
2000 Overexpression of SLAP-130 abrogates SLP-76-mediated augmentation of NFAT/AP1 activity; Tyr559 of SLAP-130 is critical for SLP-76 association, and mutation of this residue diminishes SLAP-130's negative regulatory effect on SLP-76 function, specifically through ERK activation but not PLCγ1 phosphorylation. Deletion and point mutagenesis, co-transfection in SLP-76-deficient Jurkat cells, NFAT/AP1 reporter assay, phosphorylation analysis The Journal of biological chemistry High 10671560
2001 T cells from SLAP-130/Fyb knockout mice show markedly impaired proliferation after CD3 engagement. TCR fails to enhance integrin-dependent adhesion and LFA-1 clustering is defective, while TCR-induced actin polymerization is normal. This places SLAP-130/Fyb as coupling TCR-mediated actin rearrangement with integrin (LFA-1) clustering/activation. Genetic knockout mice, T cell proliferation assay, integrin adhesion assay, LFA-1 clustering assay (flow cytometry/microscopy), actin polymerization assay Science High 11567141
2001 Fyb/Slap-deficient T cells exhibit defective proliferation, cytokine production, and TCR-induced integrin clustering and adhesion; Fyb/Slap has no apparent role in F-actin polymerization or TCR clustering. Fyb/Slap is the first adapter shown to specifically couple TCR stimulation to integrin avidity modulation. Genetic knockout mice, proliferation assay, cytokine ELISA, integrin clustering assay, F-actin assay, in vivo immune response assay Science High 11567140
2001 Upon FcεRI aggregation on mast cells, FYB becomes tyrosine-phosphorylated and colocalizes with F-actin in membrane ruffles. FYB up-regulates β1 integrin-mediated adhesion to fibronectin and mediator (β-hexosaminidase) release; the FYB SH3 domain is required for mediator release but not adhesion, distinguishing two functional outputs. Overexpression in RBL-2H3 mast cells, phosphorylation assay, adhesion assay, degranulation assay (β-hexosaminidase), confocal microscopy, SH3 domain deletion mutants Proceedings of the National Academy of Sciences of the United States of America High 11553777
2001 Upon Fcγ receptor engagement during phagocytosis in macrophages, a large molecular complex containing Fyb/SLAP, SLP-76, Nck, Ena/VASP proteins, and WASP is formed. Fyb/SLAP recruits VASP and profilin to the phagocytic cup, coordinating actin polymerization for pseudopod extension and particle internalization. Co-immunoprecipitation from macrophages, immunofluorescence microscopy at phagocytic cup, functional phagocytosis assay Journal of cell science High 11739662
2001 ADAP (FYB) promotes β1 integrin clustering kinetics on mast cells selectively; FcεRI receptor clustering was unaffected by ADAP overexpression, indicating specificity for integrins. Overexpression in mast cells, integrin clustering assay by flow cytometry/microscopy, receptor clustering controls Biochemical and biophysical research communications Medium 11741310
2003 The Yersinia tyrosine phosphatase YopH targets Fyb (FYB1) in macrophages; YopH binds Fyb in both phosphotyrosine-dependent (N-terminal YopH substrate-binding domain and C-terminal catalytic region) and phosphotyrosine-independent (central YopH region with Fyb C-terminus) manners. Dephosphorylation of Fyb by YopH contributes to blockage of phagocytosis and cytotoxic effects on macrophages. YopH mutant analysis, GST pulldown, co-immunoprecipitation in infected cells, phagocytosis assay, YopH localization assay Cellular microbiology High 12542470
2003 In mast cells, SLAP-130 and SKAP55 are the major MIST-associated phosphoproteins. MIST directly associates with SLAP-130 via MIST's SH2 domain; collaboration of SLAP-130 with SKAP55 recruits MIST to Lyn. SLAP-130/SKAP55 show higher affinity binding to Fyn-SH2 than Lyn-SH2, preferentially targeting MIST to Fyn. Co-immunoprecipitation in mast cell lines, pulldown, SH2 domain binding assay FEBS letters Medium 12681493
2004 The C-terminal domain of ADAP was solved by NMR spectroscopy as an altered SH3 fold (helically extended SH3, hSH3) in which an N-terminal amphipathic helix makes contacts to the regular SH3 scaffold. The hSH3 domain cannot bind conventional proline-rich peptides, distinguishing it functionally from canonical SH3 domains. NMR structure determination, proline-rich peptide binding assay Structure High 15062083
2004 ADAP-SLP-76 binding (via YDDV motifs) differentially regulates pSMAC formation at the immunological synapse versus T cell–APC conjugation. Mutation of YDDV sites (M12) prevents LFA-1 clustering and conjugation enhancement but acts as a dominant negative specifically for pSMAC formation and IL-2 production. ADAP colocalizes with LFA-1 at the immunological synapse. Mutagenesis (YDDV→FDDF, M12), confocal microscopy (SMAC imaging), conjugation assay, LFA-1 clustering assay, IL-2 production assay The Journal of experimental medicine High 15477347
2005 The hSH3 domain of ADAP binds acidic lipids including phosphatidylinositides (PIP2, PIP3) preferentially over monovalent PS; binding is dependent on the N-terminal helix of the hSH3 domain and basic surface patches. This identifies the hSH3 domain as a lipid interaction module. Lipid binding assay (liposome co-sedimentation), NMR chemical shift mapping, mutagenesis of basic residues Journal of molecular biology High 15843031
2005 ADAP interacts with c-Src in osteoclast precursors; c-Src kinase activity and SH2 domain are required for the association, with Tyr807 in ADAP identified as the major recognition site. ADAP is expressed in prefusion osteoclasts and localizes to lamellipodia leading edges. ADAP knockdown impairs migration and multinucleated cell formation in RAW264 cells. GST pulldown combined with mass spectrometry, co-immunoprecipitation, mutagenesis (Y807), ADAP knockdown (siRNA), migration assay, multinucleated cell formation assay The Journal of biological chemistry Medium 16020549
2005 In the absence of ADAP, SKAP55 protein is rapidly degraded (half-life ~15–20 min vs. ~90 min with ADAP). ADAP protects SKAP55 from proteolysis via the SKAP55 SH3 domain interaction with ADAP; inactivating SKAP55's SH3 domain blocks this protective effect. ADAP-deficient Jurkat line with ADAP reconstitution, pulse-chase/proteolysis assay, SH3 domain mutants The Journal of biological chemistry High 15849195
2005 Fyb (FYB1) 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 the proteins co-localize with F-actin at the leading edge. Yeast two-hybrid screen (Fyb domains as bait), co-immunoprecipitation from macrophage lysates, co-localization by immunofluorescence FEBS letters Medium 15848169
2005 TCR-stimulated ROS generation leads to transient inactivation/oxidation of SHP-2 (but not SHP-1), which directly regulates phosphorylation of Vav1 and ADAP. The ADAP–SLP-76 association is regulated by SHP-2 in a redox-dependent manner, promoting T cell adhesion through an SLP-76-dependent pathway to integrin activation. ROS assay, PTP oxidation assay, co-immunoprecipitation, phosphorylation analysis, SHP-2 knockdown/inhibition The EMBO journal Medium 15933714
2006 ADAP is required for normal αIIbβ3 activation by VWF/GP Ib-IX-V and other agonists (ADP, PAR4) in platelets. ADAP stabilizes SKAP-HOM expression via its SH3 domain interaction, but SKAP-HOM is not required for αIIbβ3 activation. ADAP-deficient mice show increased rebleeding, establishing ADAP as a component of platelet inside-out signaling. ADAP-/- mice, fibrinogen/ligand-mimetic Fab binding assay, shear-flow adhesion assay, tail-bleeding assay, SKAP-HOM-/- comparison Blood High 17003372
2006 The ADAP/SKAP55 signaling module regulates TCR-mediated integrin activation through plasma membrane targeting of activated Rap1. Disruption of the ADAP/SKAP55 interaction displaces Rap1 from the plasma membrane without affecting Rap1 GTPase activity. Membrane targeting of the ADAP/SKAP55 module induces T cell adhesion even without TCR stimulation. Mutagenesis disrupting ADAP/SKAP55 interaction, Rap1 membrane fractionation, Rap1 GTPase assay, retroviral reconstitution, adhesion assay Molecular and cellular biology High 16980616
2007 ADAP regulates TCR-mediated NF-κB activation by associating with the CARMA1 adapter. ADAP-deficient T cells show impaired NF-κB nuclear translocation, reduced IκB phosphorylation/degradation, and impaired CARMA1-BCL10-MALT1 complex assembly. A distinct region of ADAP is required for CARMA1 association and NF-κB activation, separate from the adhesion-regulatory domain. ADAP-/- mice, NF-κB nuclear translocation assay (EMSA), IκB phosphorylation/degradation assay, CBM complex assembly assay, co-immunoprecipitation, domain mutagenesis Science High 17478723
2007 RIAM constitutively interacts with SKAP-55 and is a key component linking the ADAP/SKAP-55 module to active Rap1. The ADAP/SKAP-55 module relocates RIAM and Rap1 to the plasma membrane following TCR activation. The SKAP-55/RIAM complex is essential for TCR-mediated adhesion and T cell–APC conjugate formation. Co-immunoprecipitation in primary T cells and transfection system, domain mapping of SKAP-55/RIAM interaction, subcellular fractionation, adhesion assay, conjugate formation assay Molecular and cellular biology High 17403904
2009 ADAP is an essential component of outside-in αIIbβ3 signaling in platelets under shear flow. ADAP-/- platelets show reduced spreading and unstable thrombi under shear but not under static conditions. ADAP-sufficient platelets form F-actin–rich structures co-localizing with SLP-76 and phospho-Vav1 under shear; ADAP-/- platelets fail to form these structures. VASP- or SKAP-HOM-deficient platelets do not share this phenotype. ADAP-/- mice, shear-flow platelet spreading assay, ex vivo thrombus formation, F-actin microscopy, comparison with VASP-/- and SKAP-HOM-/- mice Blood High 19996090
2009 The SLP-76–ADAP binding module is required for LFA-1-mediated outside-in costimulation of IL-2, F-actin clustering, T cell polarization, and motility. ADAP expression with LFA-1 ligation alone is sufficient to polarize T cells and increase motility; the M12 ADAP mutant (lacking SLP-76-binding sites) blocks LFA-1 costimulation of all these events. LFA-1–ADAP polarization depends on Src kinases, Rho GTPases, PLC, and PI3K. ADAP-/- T cells, ADAP M12 mutant, LFA-1 ligation assay, F-actin clustering (microscopy), polarization assay, T cell motility assay, pharmacological inhibitors Proceedings of the National Academy of Sciences of the United States of America High 19617540
2010 ADAP contains three SLP-76 SH2 domain binding sites; multipoint binding to ADAP oligomerizes the SLP-76 SH2 domain in vitro and is critical for SLP-76 microcluster assembly in T cells. Biophysical methods (AUC, SPR) quantified oligomerization, and confocal imaging confirmed all three sites are required for full microcluster formation. Analytical ultracentrifugation (AUC), SPR biophysics, mutagenesis of ADAP binding sites, confocal imaging of SLP-76 microclusters, T cell functional assays Molecular and cellular biology High 23979596
2010 ADAP is a phosphotyrosine-dependent interaction hub: peptide pulldown with SILAC mass spectrometry identified SLP-76, PLCγ, PIK3R1, Nck, CRK, Gads, and RasGAP as phospho-dependent binding partners of the central YDDV motif of ADAP. The ADAP–Nck interaction (via pY595/pY651 YDDV motifs and Nck SH2 domain) was confirmed by yeast two-hybrid, co-IP, and binary pulldown. Phosphopeptide pulldown, SILAC quantitative mass spectrometry, yeast two-hybrid, co-immunoprecipitation, binary GST pulldown PloS one High 20661443
2010 ADAP phosphorylation sites Y595, Y625, and Y771 mediate SH2-domain-based interactions with SLP-76 and other TCR proximal signaling proteins as mapped by SILAC and 18O quantitative mass spectrometry using phosphopeptide pulldowns. Novel interaction partner RasGAP was identified at phosphoY595. Phosphopeptide-agarose pulldown, SILAC quantitative MS, 18O labeling MS Journal of proteome research High 20568816
2010 HPK1 competes with ADAP for SLP-76 binding. Upon TCR stimulation, HPK1 dampens Rap1 activation, reducing LFA-1 integrin activity. HPK1-deficient T cells show increased ADAP recruitment to SLP-76, elevated Rap1 activation, and increased adhesion to ICAM-1, establishing HPK1 as a negative regulator acting at the ADAP–SLP-76 node. Co-immunoprecipitation (competition binding), HPK1-/- T cells, Rap1 GTPase assay (pull-down of active Rap1), LFA-1 adhesion assay European journal of immunology Medium 20957749
2011 Two pathways lead to SLP-76-dependent actin rearrangement in T cells: one through the SLP-76 acidic domain (Nck SH2 binding) and another through the SLP-76 SH2 domain (ADAP interaction). ADAP and Nck functionally cooperate to mediate SLP-76–WASp interactions and actin rearrangement; Nck is necessary but insufficient without ADAP. SLP-76 domain mutants, siRNA knockdown of ADAP and Nck, WASp co-immunoprecipitation, F-actin polymerization assay, confocal microscopy Molecular and cellular biology High 21536650
2011 ADAP-mediated integrin regulation requires recruitment of ADAP to the LFA-1 integrin complex through the pleckstrin homology (PH) domain of SKAP55 (specifically R131). The SKAP-ADAP chimera rescues integrin function in ADAP-/- T cells; the R131M PH domain mutation abrogates integrin rescue while paradoxically restoring NF-κB signaling, demonstrating mutually exclusive ADAP pools regulate integrin vs. NF-κB. SKAP-ADAP chimeric fusion protein, PH domain point mutation (R131M), ADAP-/- T cell reconstitution, LFA-1 co-immunoprecipitation, NF-κB reporter assay, integrin adhesion assay Journal of immunology High 21525391
2010 ADAP is critical for NF-κB activation in T cells via two distinct binding sites: one for TAK1 (required for IKK phosphorylation and IKKγ ubiquitination) and one for CARMA1 (required for IKKγ ubiquitination but not IKK phosphorylation). ADAP recruits TAK1 and the CBM complex to PKCθ but is not required for TAK1 activation itself. ADAP mutants (CARMA1-binding site, TAK1-binding site), co-immunoprecipitation of TAK1/CARMA1/PKCθ complexes, IKK phosphorylation assay, IKKγ ubiquitination assay, NF-κB nuclear translocation assay The Journal of biological chemistry High 20164171
2012 ADAP deficiency causes a G1-S transition block due to impaired accumulation of Cdk2 and cyclin E. The CARMA1-binding site in ADAP is critical for MKK7 phosphorylation, PKCθ signalosome recruitment, and JNK-mediated Cdk2 induction. Both CARMA1- and TAK1-binding sites in ADAP restrain cyclin E ubiquitination/turnover independently of JNK. ADAP-/- T cells, ADAP domain mutants (CARMA1/TAK1 sites), cell cycle analysis (flow cytometry), cyclin E ubiquitination assay, MKK7/JNK phosphorylation assay Molecular and cellular biology High 22411628
2012 SLP-76 and ADAP are required for E-selectin-mediated integrin activation and slow leukocyte rolling in neutrophils, promoting ischemia-reperfusion-induced AKI. Specifically, two N-terminal tyrosines and the SH2 domain of SLP-76 are required. Bruton's tyrosine kinase acts downstream of SLP-76, and together with ADAP regulates PI3Kγ- and PLCγ2-dependent integrin affinity and avidity regulation. Genetically engineered mice (ADAP-/-, SLP-76-/-), transduced Slp76-/- primary leukocytes, intravital microscopy (leukocyte rolling), integrin affinity/avidity assays, pharmacological inhibitors The Journal of experimental medicine High 22291096
2013 In NK cells, a Fyn–ADAP complex exclusively regulates inflammatory cytokine production but not cytotoxicity through a Carma1-Bcl-10-MAP3K7 signaling axis. Cytotoxicity requires Lck, Fyn, PI(3)K, and PLC-γ2 but is ADAP-independent, while cytokine production requires additionally the Fyn-ADAP-Carma1-Bcl-10-MAP3K7 pathway. ADAP-/- mice, NK cell cytotoxicity assay, cytokine production assay (ELISA/intracellular staining), co-immunoprecipitation of Fyn-ADAP, pharmacological inhibitors for pathway dissection Nature immunology High 24036998
2014 ADAP promotes platelet αIIbβ3 activation through novel associations with talin and kindlin-3. GST pulldowns identified distinct ADAP regions for kindlin and talin binding. ADAP-deficient platelets show reduced talin–αIIbβ3 co-localization and reduced irreversible fibrinogen binding. In CHO cells co-expressing αIIbβ3/talin/PAR1/kindlin-3, ADAP associates with the αIIbβ3/talin complex and enables kindlin-3-driven agonist-dependent ligand binding. GST pulldown (domain mapping), co-immunoprecipitation in platelets, immunofluorescence/proximity ligation assay, ADAP-/- mice, fibrinogen binding assay, CHO cell reconstitution Blood High 24523237
2015 The ADAP-SKAP55 module promotes PD-1 expression on CD8+ T cells in a Fyn-, Ca2+-, and NFATc1-dependent manner. ADAP or SKAP55 knockout reduces PD-1 in CD8+ effector T cells; the NFATc1 inhibitor CsA similarly downregulates PD-1 and enhances anti-tumor efficacy, placing ADAP upstream of the NFATc1-PD-1 axis. ADAP-/- and SKAP55-/- mice, PD-1 surface expression by flow cytometry, tumor prevention/therapeutic models, adoptive transfer, pharmacological inhibition (CsA, Fyn inhibitor, Ca2+ chelation) EMBO molecular medicine High 25851535
2015 ADAP forms a complex with TRAF6 and TAK1 in CD8+ T cells and activates SMAD3 to increase autocrine TGF-β1 production; TGF-β1 then induces CD103 expression via ADAP-, TRAF6-, and SMAD3-dependent signaling. ADAP-/- CD8+ T cells show reduced TGF-β1, CD103, and VLA-1 during influenza infection. Co-immunoprecipitation of ADAP-TRAF6-TAK1 complex, SMAD3 activation assay, TGF-β1 ELISA, CD103 expression by flow cytometry, ADAP-/- mice with influenza infection model PLoS pathogens High 25909459
2015 Phosphorylation of ADAP at pY571 attracts ZAP70 (via its N-terminal SH2 domain, Kd = 2.3 μM by microscale thermophoresis); this interaction is inducible by TCR or chemokine stimulation. Y571 mutation specifically impairs chemokine-induced T cell migration but does not affect TCR-dependent T cell–APC conjugate formation or adhesion. Phosphopeptide pulldown, NMR spectroscopy (SH2 domain interaction mapping), microscale thermophoresis (Kd determination), Y571F mutagenesis, T cell migration assay, conjugate/adhesion assay Molecular & cellular proteomics High 26246585
2017 Ubc9 (SUMO E2 conjugase) directly interacts with ADAP in vitro and in vivo via a nuclear localization sequence (aa 674–700) of ADAP; interaction increases after TCR stimulation. Ubc9 knockdown or expression of Ubc9-binding-deficient ADAP reduces TCR-induced integrin adhesion, LFA-1 clustering, Rac1 activation, and membrane targeting of Rap1/RapL, without affecting TCR proximal signaling or IL-2. GST pulldown (in vitro direct binding), co-immunoprecipitation in vivo, domain mapping, Ubc9 shRNA knockdown, Rac1 activation assay (pulldown), Rap1/RapL membrane fractionation, LFA-1 clustering assay Journal of immunology High 29127148
2018 ADAP acts as an upstream regulator of SLP-76 microcluster formation; pY595-ADAP enters SLP-76 microclusters while non-phosphorylated ADAP is pre-positioned in actin-rich protrusive structures at contact sites. Multivalent ADAP–SLP-76 SH2 interactions sustain ADAP phosphorylation. ADAP promotes integrin-independent adhesion and CD69 upregulation. A novel phospho-specific antibody confirmed that virtually all ADAP tyrosine phosphorylation is restricted to pY595. TIRF microscopy, phospho-specific antibody generation, point mutants (Y595F), live cell imaging, integrin-independent adhesion assay, CD69 expression assay Journal of cell science High 30305305
2018 ADAP deficiency impairs megakaryocyte polarization and causes ectopic proplatelet release into the bone marrow compartment, leading to microthrombocytopenia. ADAP-deficient MKs show reduced spreading on ECM proteins, impaired β1 integrin activation, and defective podosome formation. MK-specific ADAP KO (PF4-Cre) recapitulates the platelet phenotype, confirming an MK-intrinsic defect. Constitutive and PF4-Cre conditional ADAP KO mice, 3D confocal imaging of sternum, intravital 2-photon microscopy, in vitro MK spreading/podosome assay, β1 integrin activation assay, DMS polarization assay Blood High 29950291
2021 ADAP phosphorylation at Y571 (in the YDSL motif, induced by LPS/TLR4) is required for STAT3 coactivation in macrophages. ADAP interacts with STAT3 and its loss reduces LPS-mediated STAT3 phosphorylation and IL-6-induced STAT3 activation. Y571F mutation abolishes ADAP's stimulating effect on STAT3 and its inhibition of M1-like macrophage polarization. ADAP-/- macrophages, Y571F mutagenesis, ADAP overexpression, STAT3 phosphorylation assay, co-immunoprecipitation (ADAP-STAT3), cytokine ELISA, macrophage polarization assay Journal of immunology High 33431658
2022 ADAP restrains platelet phagocytosis by macrophages via modulation of STAT1-FcγR signaling. ADAP interacts with STAT1 and competes with STAT1 binding to importin α5, reducing STAT1 nuclear entry. ADAP deficiency potentiates STAT1 nuclear translocation and selectively enhances FcγRI/IV transcription in macrophages. ADAP-/- mice, macrophage depletion, co-immunoprecipitation (ADAP-STAT1, STAT1-importin α5 competition assay), STAT1 nuclear fractionation, FcγRI/IV transcription analysis, pharmacological STAT1 inhibition Cellular & molecular immunology High 35637282
2024 ADAP selectively interacts with and cooperates functionally with RIG-I (but not MDA5) to activate IFN-β transcription in macrophages. ADAP inhibits ISGylation (ISG15 conjugation) of RIG-I; ADAP deficiency increases RIG-I ISGylation, decreases IRF3/TBK1 phosphorylation, and impairs IFN-β induction upon RNA virus infection. Co-immunoprecipitation (ADAP-RIG-I), ISGylation assay (in vitro/in vivo), ADAP-/- mice, RNA virus infection model, IRF3/TBK1 phosphorylation assay, IFN-β ELISA PLoS pathogens High 38776321
2025 ADAP is required for TLR4-induced upregulation of podoplanin (PDPN) in macrophages. BTK-mediated tyrosine phosphorylation of ADAP at Y571, together with mTOR, converges on STAT3 activation for transactivation of the PDPN promoter. ADAP deficiency prevents generation of a PDPNhi M2-like macrophage subset with enhanced phagocytic activity, exacerbating sepsis. ADAP-/- mice, ADAP reconstitution, BTK inhibitor, mTOR inhibitor, Y571 mutagenesis, STAT3 phosphorylation assay, PDPN promoter transactivation assay, peritoneal macrophage phenotyping, sepsis model JCI insight High 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.) 251 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 247 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.) 229 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 81 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 76 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 75 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 68 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 57 11973129
2014 ADAP interactions with talin and kindlin promote platelet integrin αIIbβ3 activation and stable fibrinogen binding. Blood 55 24523237
2015 ADAP and SKAP55 deficiency suppresses PD-1 expression in CD8+ cytotoxic T lymphocytes for enhanced anti-tumor immunotherapy. EMBO molecular medicine 53 25851535
2000 Functional association between SLAP-130 and SLP-76 in Jurkat T cells. The Journal of biological chemistry 52 10671560
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 44 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 39 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 28 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
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) 23 25727406
2004 Structure of a helically extended SH3 domain of the T cell adapter protein ADAP. Structure (London, England : 1993) 23 15062083
2022 ADAP restraint of STAT1 signaling regulates macrophage phagocytosis in immune thrombocytopenia. Cellular & molecular immunology 22 35637282
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
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
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 15 22119473
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
2023 Super Enhancer Regulatory Gene FYB1 Promotes the Progression of T Cell Acute Lymphoblastic Leukemia by Activating IGLL1. Journal of immunology research 14 37767202
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
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
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 11 24530029
2011 TM4SF10 and ADAP interaction in podocytes: role in Fyn activity and nephrin phosphorylation. American journal of physiology. Cell physiology 11 21881001
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
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
2020 ADAP Promotes Degranulation and Migration of NK Cells Primed During in vivo Listeria monocytogenes Infection in Mice. Frontiers in immunology 9 32038647
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
2012 The adapter protein ADAP is required for selected dendritic cell functions. Cell communication and signaling : CCS 9 22672517
2009 ADAP deficiency combined with costimulation blockade synergistically protects intestinal allografts. Transplant international : official journal of the European Society for Organ Transplantation 9 19678902
2019 Characterization of Mice with a Platelet-Specific Deletion of the Adapter Molecule ADAP. Molecular and cellular biology 8 30833485
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
2021 FYB methylation in peripheral blood as a potential marker for the early-stage lung cancer: a case-control study in Chinese population. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 5 34882057
2016 Integrin Activation Through the Hematopoietic Adapter Molecule ADAP Regulates Dendritic Development of Hippocampal Neurons. Frontiers in molecular neuroscience 5 27746719

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