Affinage

TYROBP

TYRO protein tyrosine kinase-binding protein · UniProt O43914

Length
113 aa
Mass
12.2 kDa
Annotated
2026-04-28
100 papers in source corpus 46 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TYROBP (DAP12) is a disulfide-linked homodimeric transmembrane adaptor protein that uses its cytoplasmic ITAM to transduce activating signals from a broad repertoire of immune and bone-cell receptors, thereby coordinating NK cell cytotoxicity, osteoclast differentiation, macrophage fusion and chemotaxis, and microglial homeostasis. DAP12 pairs non-covalently with receptors including NKG2C, Ly49D/H, NKp44, TREM-2, SIRPβ1, MDL-1, Siglec-15, and MAIR-II through complementary charged transmembrane residues; upon receptor engagement, Src-family kinases phosphorylate the ITAM, recruiting Syk (or ZAP-70), which activates PLCγ, ERK, PI3K/Akt, and calcium mobilization cascades (PMID:9655483, PMID:9830044, PMID:11241283, PMID:22451653). DAP12 also negatively regulates TLR-driven inflammation through the adaptor DOK3 and Syk, and in microglia it restrains complement accumulation and wound-healing transcriptional programs; accordingly, loss-of-function mutations in TYROBP cause Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy), characterized by bone cysts and presenile dementia (PMID:10888890, PMID:15895090, PMID:23962980, PMID:36658241). Myeloid-specific transcription of DAP12 is driven by PU.1 binding to conserved promoter elements (PMID:17827340).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1998 High

    Identification of DAP12 as a disulfide-linked homodimeric ITAM-bearing transmembrane adaptor that pairs with activating NK receptors (NKG2C, Ly49D/H) via charged transmembrane residues established the gene's fundamental signaling architecture and receptor-pairing mechanism.

    Evidence Co-immunoprecipitation with transmembrane domain mutagenesis, ITAM point mutations abolishing signaling, and dominant-negative Syk blocking downstream phosphorylation in transfected and NK cell systems

    PMID:9647200 PMID:9655483 PMID:9830044 PMID:9852069

    Open questions at the time
    • Crystal structure of DAP12 transmembrane domain in complex with a paired receptor was not determined
    • Precise stoichiometry of receptor–DAP12 complexes in native membranes unresolved
  2. 1998 High

    Mapping the DAP12 signaling cascade revealed that Syk (not ZAP-70) is the primary kinase downstream of the ITAM, activating PLCγ1, MAPK (ERK), Cbl, and calcium mobilization, defining the core signaling module.

    Evidence Dominant-negative Syk transfection blocking phosphorylation of PLCγ1, p44/p42 MAPK, and calcium flux upon Ly49D/DAP12 ligation

    PMID:9830044

    Open questions at the time
    • Relative contributions of Syk vs. ZAP-70 in cell types expressing both kinases not fully dissected
    • Structural basis for Syk preference over ZAP-70 unknown
  3. 1999 High

    Discovery of MDL-1, SIRPβ1, and Ly49H as additional DAP12-paired receptors with functional calcium and cytokine readouts expanded the adaptor's role beyond classical NK receptors to myeloid cells.

    Evidence Co-IP and calcium mobilization/TNF secretion assays in macrophage and transfected cell lines

    PMID:10411005 PMID:10449773 PMID:10940905

    Open questions at the time
    • Endogenous ligands for MDL-1 and SIRPβ1 not identified
    • Whether all myeloid DAP12-paired receptors use identical downstream signaling arms was unclear
  4. 2000 High

    Human genetics established that TYROBP loss-of-function causes Nasu-Hakola disease (PLOSL), revealing essential non-redundant roles in bone and brain beyond NK cell killing.

    Evidence Identification of a large deletion in Finnish patients and a point mutation in a Japanese patient; NK cytotoxicity was preserved

    PMID:10888890

    Open questions at the time
    • Why bone cysts and dementia but not overt immunodeficiency occur in patients was mechanistically unexplained
    • Cell-type-specific requirement (osteoclast vs. microglia) not dissected
  5. 2000 High

    ITAM-dead knockin mice demonstrated non-redundant DAP12 roles in NK cytotoxicity and dendritic cell homeostasis, and distinguished DAP12 from the neighboring adaptor DAP10 which signals through PI3K/Akt.

    Evidence KARAP/DAP12 ITAM knockin mice showing restricted NK killing and DC accumulation; DAP10 reconstitution studies with transmembrane domain swaps

    PMID:10528161 PMID:11015446 PMID:11021533

    Open questions at the time
    • Molecular basis for DC accumulation phenotype not mechanistically defined
    • Whether DAP10 and DAP12 ever form hetero-complexes was unresolved
  6. 2001 High

    TREM-2 was identified as a macrophage DAP12-paired receptor, establishing the partnership that would prove central to osteoclast and microglial biology.

    Evidence cDNA library screen using DAP12-dependent surface expression, co-IP with endogenous DAP12, nitric oxide release assay

    PMID:11241283

    Open questions at the time
    • TREM-2 ligand identity unknown at this point
    • Whether TREM-2/DAP12 operates identically in microglia vs. macrophages was untested
  7. 2002 High

    DAP12 ITAM mutant mice showed 30–40-fold higher MCMV viral titers, demonstrating that Ly49H/DAP12 signaling is essential for NK-mediated antiviral resistance in vivo.

    Evidence ITAM knockin mice infected with MCMV; splenic viral titer and hepatic NK IFN-γ measurements

    PMID:11927627

    Open questions at the time
    • Whether DAP12 contributes to resistance against other viral infections was not tested
    • Downstream effector mechanisms beyond IFN-γ not mapped
  8. 2003 High

    DAP12-knockout mice and PLOSL patient cells showed that DAP12–Syk signaling is required for osteoclast multinucleation, cytoskeletal organization (via c-Src/Pyk2), and bone resorption, explaining the bone cyst phenotype of Nasu-Hakola disease.

    Evidence DAP12 KO mice with osteopetrosis, retroviral DAP12 reconstitution rescuing multinucleation, Syk/c-Src/Pyk2 phosphorylation assays, patient-derived osteoclast cultures

    PMID:12569157 PMID:12925681 PMID:14624447 PMID:14969392

    Open questions at the time
    • Which specific DAP12-paired receptor(s) are rate-limiting for osteoclast fusion was not resolved
    • Upstream osteopontin receptor linking to DAP12 phosphorylation was unclear
  9. 2004 High

    DAP12 expression in microglia (not neurons or astrocytes) was shown to regulate synaptic AMPA receptor composition, LTP magnitude, and TrkB levels, establishing a non-cell-autonomous microglia-to-neuron signaling axis.

    Evidence DAP12 KO mice with electrophysiology (enhanced LTP, altered AMPAR rectification), biochemical fractionation of postsynaptic densities, cell-type-specific immunostaining

    PMID:15601948

    Open questions at the time
    • Molecular intermediates between microglial DAP12 signaling and postsynaptic receptor changes were not identified
    • Whether this reflects a developmental or ongoing homeostatic role was unclear
  10. 2004 High

    NKp44 was shown to require DAP12 association via transmembrane Lys-183 for surface expression and activation, while human NKG2D was confirmed to be DAP12-independent (using DAP10 exclusively), resolving a species-specific discrepancy.

    Evidence Transmembrane domain mutagenesis of NKp44 and NKG2D chimeric constructs; validation using DAP12-deficient human patients

    PMID:14707061 PMID:15294961

    Open questions at the time
    • Complete inventory of human vs. mouse DAP12-dependent receptors not systematically compiled
  11. 2005 High

    DAP12 was discovered to negatively regulate TLR signaling: DAP12-deficient and Syk-deficient macrophages both produced elevated inflammatory cytokines upon TLR stimulation, revealing an unexpected anti-inflammatory arm of ITAM signaling.

    Evidence DAP12 KO and Syk KO macrophages showing identical hyper-inflammatory phenotype upon LPS stimulation; in vivo endotoxic shock model

    PMID:15895090

    Open questions at the time
    • Molecular intermediary between Syk and TLR suppression not yet identified (DOK3 would come later)
    • Whether all DAP12-paired receptors participate in TLR cross-regulation was unknown
  12. 2006 High

    Src-family kinases Fyn and Lck were identified as the proximal kinases phosphorylating DAP12, and CD45 was shown to dephosphorylate DAP12, establishing the kinase–phosphatase balance governing ITAM activation.

    Evidence Co-IP from primary NK cells, Fyn/Lck KO mice, CD45-null NK cells showing hyperphosphorylated DAP12 with defective downstream signaling

    PMID:16709819

    Open questions at the time
    • Whether other phosphatases contribute to DAP12 dephosphorylation in myeloid cells was untested
    • How CD45 accesses DAP12 at the membrane-proximal ITAM structurally unclear
  13. 2007 High

    PU.1 was identified as the transcription factor driving myeloid-specific DAP12 expression through conserved promoter elements, explaining the lineage-restricted expression pattern.

    Evidence Promoter mutagenesis, EMSA, ChIP, PU.1 RNAi reducing endogenous DAP12, PU.1−/− progenitor reconstitution inducing DAP12

    PMID:17827340

    Open questions at the time
    • Whether additional transcription factors cooperate with PU.1 for microglial DAP12 expression was not examined
  14. 2008 High

    DAP12/TREM-2/Syk signaling was shown to be required for macrophage fusion into multinucleated giant cells by regulating DC-STAMP and Cadherin-1, unifying the osteoclast and macrophage fusion phenotypes.

    Evidence DAP12 KO macrophages failing to fuse; DAP12 overexpression potentiating fusion with modulation of fusion mediator gene expression

    PMID:18957693

    Open questions at the time
    • Whether DC-STAMP is a direct or indirect transcriptional target of Syk signaling was unclear
  15. 2010 High

    Detailed dissection of TREM2/DAP12 signaling revealed that DAP10 is required for PI3K recruitment to the complex, SHIP1 acts as a negative regulator by blocking PI3K, and DAP12 ITAM phosphorylation is required for macrophage chemotaxis toward CCL2.

    Evidence PI3K recruitment co-IP, SHIP1 SH2 domain mutant analysis, Vav3 activation assay, DAP12 KO macrophage chemotaxis with ITAM mutant reconstitution, in vivo airway migration

    PMID:20421649 PMID:20484116

    Open questions at the time
    • How DAP10 is recruited to the TREM2/DAP12 complex at the molecular level was not structurally resolved
    • Relative importance of PI3K vs. Syk arms for different functional outputs not fully separated
  16. 2012 High

    Siglec-15 was identified as a DAP12-paired receptor using conserved transmembrane lysine (Lys-274), and the Siglec-15/DAP12/Syk cascade was shown to drive both osteoclast bone resorption and TGF-β secretion upon sialyl-Tn recognition on tumors.

    Evidence Transmembrane K274A mutagenesis, co-IP, chimeric receptor rescue, Syk inhibitor, bone resorption and cytokine assays

    PMID:22451653 PMID:23035012

    Open questions at the time
    • Whether Siglec-15/DAP12 has immunomodulatory roles in vivo beyond tumor microenvironment not tested
  17. 2013 High

    DOK3 was identified as the molecular intermediary of DAP12-mediated TLR suppression: DOK3 binds the DAP12 ITAM via its PTB domain, is phosphorylated by Src kinases, and translocates to the plasma membrane to dampen inflammatory cytokine production.

    Evidence ITAM pulldown co-IP, DOK3 KO macrophages and mice with elevated cytokines, phosphorylation and translocation assays

    PMID:23962980

    Open questions at the time
    • Downstream effectors of DOK3 at the plasma membrane not identified
    • Whether DOK3 mediates all DAP12 inhibitory functions or only TLR cross-talk unresolved
  18. 2014 High

    αvβ3 integrin engagement was shown to induce DAP12 ITAM phosphorylation in osteoclasts, and combined DAP12/β3 deletion caused severe osteopetrosis that OSCAR/FcRγ could not rescue, demonstrating integrin–ITAM signaling convergence.

    Evidence β3/DAP12 double-KO mice, Syk phosphorylation assay, OSCAR rescue experiments, bone density analysis

    PMID:25547154

    Open questions at the time
    • How integrin occupancy triggers DAP12 ITAM phosphorylation mechanistically (direct association or indirect) was unclear
  19. 2015 High

    DAP12 was shown to stabilize TREM2 C-terminal fragment (a γ-secretase substrate) and to function downstream of CSF1R in microglia for neuropathic pain gene induction, demonstrating distinct microglial signaling contexts.

    Evidence Co-expression with interaction mutant showing loss of TREM2-CTF stabilization; DAP12 KO mice with intrathecal CSF1 failing to induce pain-related microglial genes

    PMID:25957402 PMID:26642091

    Open questions at the time
    • Whether DAP12 directly associates with CSF1R or acts through an intermediary receptor was not established
    • Functional consequences of TREM2-CTF stabilization vs. degradation not fully elucidated
  20. 2017 High

    In Alzheimer's disease models, TYROBP deficiency prevented complement C1q accumulation, suppressed disease-associated microglia (DAM) gene induction, and preserved electrophysiological function and learning, positioning DAP12 as a central hub for microglial activation in neurodegeneration.

    Evidence TYROBP KO crossed to APP/PSEN1 mice; transcriptomics, complement staining, electrophysiology, behavioral assays; agonistic anti-TREM2 antibody in WT vs. DAP12 KO confirming pathway directionality

    PMID:27798193 PMID:28612290 PMID:30283032

    Open questions at the time
    • Whether DAP12 deletion would be beneficial or detrimental long-term in human AD was unknown
    • Which DAP12-paired receptor(s) drive C1q accumulation not identified
  21. 2023 High

    Single-nucleus transcriptomics of human NHD brains revealed that DAP12 deficiency drives microglia into a wound-healing state (RUNX1/STAT3/TGF-β) with secondary effects on astrocytes, oligodendrocyte myelination, and pericytes, establishing the cell-type-resolved consequences of human DAP12 loss in the CNS.

    Evidence snRNA-seq of NHD patient and DAP12-signaling-deficient mouse brain tissue

    PMID:36658241

    Open questions at the time
    • Causal chain from DAP12 loss to pericyte and oligodendrocyte pathology not mechanistically defined
    • Whether wound-healing microglial state is pathogenic or compensatory is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for DAP12 transmembrane domain selectivity among its >10 paired receptors, the identity of endogenous ligands for several DAP12-paired receptors (MDL-1, MAIR-II), and whether therapeutic modulation of DAP12 signaling can alter neurodegeneration in humans remain open questions.
  • No high-resolution structure of full-length DAP12 in complex with any paired receptor
  • Endogenous ligands for MDL-1, MAIR-II, and several other DAP12-paired receptors not identified
  • Therapeutic potential of DAP12 modulation in Alzheimer's disease untested in humans

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 8 GO:0060089 molecular transducer activity 4
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-168256 Immune System 6 R-HSA-112316 Neuronal System 5
Partners
DOK3HCSTKLRC2NCR2SIGLEC15SIRPB1SYKTREM2
Complex memberships
Ly49H/DAP12NKG2C/CD94/DAP12Siglec-15/DAP12TREM-2/DAP12

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 DAP12 (TYROBP) associates non-covalently with the activating NK cell receptor CD94/NKG2C; charged residues in the transmembrane domains of DAP12 and NKG2C are required for this interaction, and DAP12 is necessary for efficient cell-surface expression of CD94/NKG2C. Co-immunoprecipitation, transfection studies with transmembrane domain mutants, flow cytometry Immunity High 9655483
1998 Mouse DAP12 associates with Ly-49D and Ly-49H activating NK cell receptors; co-transfection of Ly-49D or Ly-49H with DAP12 induces surface expression of both proteins, and cross-linking the complex induces tyrosine phosphorylation of multiple cellular substrates. Co-immunoprecipitation from transfected cells, functional phosphorylation assay Journal of Immunology High 9647200
1998 DAP12-mediated signal transduction in NK cells proceeds predominantly through the Syk protein tyrosine kinase (not ZAP-70); ligation of Ly49D/DAP12 leads to tyrosine phosphorylation of PLCγ1, Cbl, and p44/p42 MAPK, as well as calcium mobilization, and these events are blocked by dominant-negative Syk. In vitro signaling assays, dominant-negative kinase transfection, immunoprecipitation, calcium flux assay Journal of Biological Chemistry High 9830044
1998 Mouse KARAP/DAP12 is a signaling transmembrane subunit whose transduction function depends on the integrity of its intracytoplasmic ITAM; point mutations disrupting the ITAM abolish signaling. DAP12 is a disulfide-linked homodimer expressed broadly in hematopoietic cells. Point mutation and transfection studies, ITAM mutagenesis Journal of Biological Chemistry High 9852069
1999 MDL-1, a C-type lectin myeloid receptor, associates with DAP12 through a charged transmembrane residue; MDL-1/DAP12 complex cross-linking results in calcium mobilization in J774 macrophage cells. Molecular cloning, co-expression/co-IP, calcium mobilization assay PNAS High 10449773
1999 Ly49H associates with DAP12; engagement of the Ly49H/DAP12 complex results in DAP12 phosphorylation, intracellular calcium mobilization, and TNF secretion in transfected cells. Co-immunoprecipitation, phosphorylation assay, calcium mobilization, TNF secretion assay Journal of Leukocyte Biology High 10411005
1999 KAP10 (DAP10), encoded within 100 bp of the DAP12 locus, is a distinct transmembrane adapter that signals through PI3K/Akt via a YINM motif—distinct from DAP12's ITAM-based Syk/ZAP-70 pathway. Molecular cloning, transfection, co-IP, Akt activation assay Journal of Immunology High 10528161
2000 Loss-of-function mutations (a large deletion in Finnish patients and a point mutation in a Japanese patient) in TYROBP (DAP12) cause Nasu-Hakola disease (presenile dementia with bone cysts), establishing DAP12 as an essential signaling element beyond NK cells. Human genetic analysis, deletion/mutation identification, functional NK cell assays showing no NK defect Nature Genetics High 10888890
2000 DAP10 and DAP12 form distinct, receptor-specific complexes in NK cells; their transmembrane regions are sufficient to confer specific association with respective partners. Synergy exists in cytokine production when both DAP10- and DAP12-associated receptors are co-engaged, with DAP12 activating Syk/ZAP70 and DAP10 activating PI3K. Receptor reconstitution in transfectants, co-IP, cytotoxicity and cytokine production assays Journal of Experimental Medicine High 11015446
2000 SIRPβ1 forms an oligomeric complex with DAP12 in monocytes and transfected cells; SIRPβ1 engagement via DAP12 recruits Syk and triggers serotonin release, establishing SIRPβ1 as an activating DAP12-paired receptor. Co-immunoprecipitation, Syk recruitment assay, degranulation assay in RBL transfectants European Journal of Immunology High 10604985 10940905
2000 KARAP/DAP12 loss-of-function (nonfunctional ITAM knockin) mice exhibit restricted NK cell natural cytotoxicity and dramatic accumulation of dendritic cells in mucocutaneous epithelia, demonstrating specific non-redundant roles in innate immunity. Knockin mouse model, NK cytotoxicity assays, DC subset analysis, contact sensitivity assays Immunity High 11021533
2001 TREM-2 is a DAP12-associated receptor expressed in mouse macrophages; cross-linking of TREM-2a on macrophage surfaces leads to nitric oxide release, demonstrating functional signaling through the TREM-2/DAP12 complex. cDNA library screening using DAP12 surface expression as readout, co-IP of TREM-2a with endogenous DAP12, nitric oxide release assay European Journal of Immunology High 11241283
2003 DAP12-deficient mice develop osteopetrosis (increased bone mass) and thalamic hypomyelinosis; in vitro osteoclast induction from DAP12−/− bone marrow yields immature cells with attenuated bone resorption, indicating a developmental arrest of osteoclasts and oligodendrocytes. DAP12 knockout mouse, bone density analysis, in vitro osteoclastogenesis, electrophysiology, prepulse inhibition assay Journal of Clinical Investigation High 12569157
2003 DAP12 signaling regulates multinucleation of osteoclasts; DAP12−/− precursors form only mononuclear osteoclast-like cells with reduced bone resorption, and retroviral reconstitution of DAP12 rescues multinucleation. TREM2 is identified as a DAP12-associated receptor on osteoclasts. DAP12 knockout mouse, retroviral reconstitution, in vitro osteoclastogenesis, bone resorption assay, RT-PCR for DAP12-associated receptors Journal of Bone and Mineral Research High 14969392
2003 Loss-of-function mutations in DAP12 or TREM2 result in inefficient and delayed osteoclast differentiation with markedly reduced bone resorption capability in vitro, from peripheral blood mononuclear cells of PLOSL patients. In vitro osteoclastogenesis from patient-derived cells, bone resorption assay Journal of Experimental Medicine High 12925681
2003 DAP12-deficient osteoclast precursors fail to differentiate normally; when plated on osteopontin, DAP12−/− pre-osteoclasts do not activate Syk, and fail to phosphorylate c-Src or Pyk2, which are required for osteoclast cytoskeletal organization. Syk-deficient macrophages also fail to undergo normal osteoclastogenesis. DAP12 knockout mouse, Syk kinase assay, phosphorylation of c-Src/Pyk2, migration assay, cytoskeletal analysis Journal of Cellular Biochemistry High 14624447
2003 In activated mouse NK cells, NKG2D associates with both DAP10 and DAP12; the DAP10-PI3K pathway is sufficient for NKG2D-mediated cytotoxicity in cells lacking DAP12 or Syk/ZAP70, whereas DAP12 is required for cytokine production, demonstrating functional divergence. DAP12 knockout mice, Syk/ZAP70 double-knockout mice, PI3K inhibition, NK cell cytotoxicity and cytokine assays Nature Immunology High 12740576
2004 KARAP/DAP12 is expressed exclusively in microglia (not neurons, astrocytes, or oligodendrocytes) in the brain; DAP12/KARAP deficiency alters synaptic glutamate receptor content (decreased GluR2 in postsynaptic densities, increased GluR2-lacking AMPARs), enhances LTP, and reduces synaptic TrkB levels, demonstrating a microglia-neuron signaling role. DAP12 knockout mouse, electrophysiology (LTP, AMPAR rectification, NMDAR pharmacology), biochemical fractionation, cell-type specific immunostaining Journal of Neuroscience High 15601948
2004 NKp44 surface expression and NK cell activation requires noncovalent association with DAP12 via lysine-183 in the NKp44 transmembrane domain; the ITIM-like motif in NKp44's cytoplasmic domain lacks inhibitory capacity and does not affect activation. Transmembrane domain mutagenesis, co-IP, redirected cytotoxicity assay, pervanadate phosphorylation, surface expression analysis Journal of Immunology High 14707061
2004 Mouse NKG2D associates with DAP12 via structural features in its transmembrane domain; human NKG2D cannot associate with DAP12 due to structural differences in its transmembrane region, and human NKG2D function is normal in DAP12-deficient patients, showing DAP10 is sufficient for human NKG2D signaling. Human patient studies (DAP12-deficient), transmembrane chimeric constructs, co-IP Journal of Immunology High 15294961
2005 DAP12-deficient macrophages produce higher concentrations of inflammatory cytokines in response to TLR stimulation; Syk-deficient macrophages show an identical phenotype, demonstrating that DAP12 negatively regulates TLR signaling through Syk downstream of DAP12-pairing receptors. DAP12 and Syk knockout mouse macrophages, TLR stimulation cytokine production assays, endotoxic shock model Nature Immunology High 15895090
2005 Plexin-A1 associates with TREM-2 and links semaphorin signaling to DAP12/ITAM pathway in dendritic cells and osteoclasts, revealing a novel receptor-adapter interaction with roles in both immune responses and bone homeostasis. Plexin-A1 knockout mice, co-immunoprecipitation of plexin-A1 with TREM-2/DAP12 complex, bone and immune phenotyping Nature Cell Biology High 16715077
2006 Src-family kinases (Fyn and Lck) physically associate with and phosphorylate the Ly49D/DAP12 complex; CD45 acts as a phosphatase for DAP12 itself, and CD45-null NK cells show hyperphosphorylated DAP12 with defective calcium mobilization and cytokine production upon Ly49D ligation. Co-immunoprecipitation from NK cells, Src kinase inhibition, Fyn/Lck knockout mice, CD45-null NK cell analysis Journal of Immunology High 16709819
2007 Non-T cell activation linker (NTAL) is phosphorylated downstream of TREM-1/DAP12 engagement in myeloid cells; NTAL knockdown enhances ERK1/2 phosphorylation and reduces calcium mobilization, and increases TNF-α and IL-8 production, identifying NTAL as a negative regulator of DAP12-mediated signaling. RNA interference knockdown, phosphorylation assays, calcium mobilization assay, cytokine ELISA in myeloid cell lines and primary granulocytes Journal of Immunology High 17277102
2008 DAP12 signaling through TREM-2 and downstream Syk is required for cytokine-induced macrophage fusion into multinucleated giant cells; DAP12 overexpression potentiates fusion and modulates expression of fusion mediators DC-STAMP and Cadherin-1. DAP12 knockout mice, Syk genetic analysis, overexpression, gene expression profiling Science Signaling High 18957693
2009 MDL-1 associates with both DAP12 and DAP10 in osteoclasts, forming trimolecular MDL-1/DAP12/DAP10 complexes; DAP10-deficient mice develop osteopetrosis with reduced osteoclasts, and MDL-1 stimulation augments osteoclastogenesis in vitro. DAP10 knockout mice, co-IP of trimolecular complex, in vitro osteoclastogenesis assay, bone density analysis PNAS High 19251634
2010 TREM2 ligation activates PI3K, ERK1/2, and Vav3, induces intracellular calcium mobilization and actin reorganization downstream of DAP12. DAP10 is required for TREM2/DAP12-dependent PI3K recruitment to the signaling complex. SHIP1 inhibits this pathway by binding DAP12 in an SH2-dependent manner and blocking PI3K recruitment. TREM2 ligation assays, PI3K recruitment co-IP, Vav3 activation assay, calcium flux, actin staining, SHIP1 SH2 domain mutant analysis Science Signaling High 20484116
2010 DAP12 is required for macrophage chemotaxis toward CCL2 and recruitment to the lung; ITAM phosphorylation of DAP12 is required for normal migration, and TREM2 association with DAP12 is sufficient to restore migration, establishing DAP12 as a regulator of macrophage chemotaxis. DAP12 knockout mice, scratch assay, CCL2 chemotaxis assay, airway CCL2 challenge, reconstitution with ITAM phosphorylation mutants Journal of Immunology High 20421649
2011 OSCAR (osteoclast-associated receptor) is an FcRγ-associated DAP12-independent costimulatory receptor in osteoclastogenesis; in DAP12-deficient humans and mice, OSCAR-FcRγ pathway compensates for osteoclast maturation, and OSCAR's ligand is identified as specific motifs in fibrillar collagens in bone ECM. DAP12-deficient patient/mouse samples, OSCAR knockout mice, collagen binding assay, in vitro osteoclastogenesis, in vivo bone analysis Journal of Clinical Investigation High 21841309
2011 MAIR-II (CD300d) is a DAP12-associated receptor on B cells; DAP12-deficient B cells show enhanced proliferation, and a chimeric MAIR-II-DAP12 receptor suppresses BCR-mediated proliferation by recruiting SHP-1, establishing that DAP12-coupled MAIR-II negatively regulates B cell adaptive immune responses. DAP12 knockout mice and human NHD patient B cells, chimeric receptor reconstitution, SHP-1 co-IP, proliferation assays Journal of Experimental Medicine High 21727189
2012 Siglec-15 associates with DAP12 through Lys-274 (Lys-272 in mouse) in its transmembrane domain, forming a Siglec-15-DAP12-Syk signaling cascade; this complex is required for functional osteoclast formation, actin-ring organization, and bone resorption. Co-IP, transmembrane domain mutagenesis (K272A), siRNA knockdown, chimeric receptor rescue, bone resorption assay Journal of Biological Chemistry High 22451653
2012 Siglec-15 signals through DAP12-Syk to enhance TGF-β secretion from monocytes/macrophages upon recognition of sialyl-Tn tumor antigen; disruption of Siglec-15/DAP12 interaction (K274A mutant) or Syk inhibition abrogates this response. Co-culture model, Syk inhibitor, K274A Siglec-15 mutant, cytokine ELISA Glycobiology High 23035012
2013 DOK3 physically associates with the ITAM of DAP12 through its phosphotyrosine-binding domain; upon LPS stimulation, DAP12- and Src-dependent phosphorylation of DOK3 leads to its translocation to the plasma membrane, and DOK3 deficiency increases proinflammatory cytokine production, establishing DOK3 as a mediator of DAP12's inhibitory function at TLR4. Co-IP (DAP12 ITAM pulldown), phosphorylation assays, DOK3 knockout macrophages and mice, cytokine assays Science Signaling High 23962980
2015 DAP12 stabilizes the C-terminal fragment of TREM2 (TREM2-CTF), a γ-secretase substrate; a DAP12 mutant that cannot interact with TREM2 fails to stabilize TREM2-CTF. Silencing Trem2 or Dap12 exacerbates LPS-induced pro-inflammatory responses in microglia. Co-expression and co-IP with interaction mutant, siRNA knockdown, LPS stimulation cytokine assay Journal of Biological Chemistry High 25957402
2015 DAP12 is required in microglia downstream of CSF1R for nerve injury- and intrathecal CSF1-induced upregulation of pain-related microglial genes and neuropathic pain behaviors, but not for microglial proliferation. DAP12 knockout mice, conditional Csf1 deletion in sensory neurons, intrathecal CSF1 injection, behavioral pain assays, microglial gene expression profiling Nature Neuroscience High 26642091
2007 Btk is phosphorylated upon TREM-1/DAP12 engagement; Btk knockdown reduces ERK1/2 and PLCγ1 phosphorylation and Ca2+ mobilization after TREM-1 stimulation, and impairs TNF-α and IL-8 production, identifying Btk as a positive regulator in the TREM-1/DAP12 ITAM signaling pathway. shRNA knockdown, Btk knockout mouse BMDCs, phosphorylation assays, Btk domain mutants, cytokine ELISA, human XLA patient cells Blood High 21659545
2007 KARAP/DAP12 plays a pivotal role in NK cell-mediated resistance to murine CMV infection via the Ly49H/DAP12-associated receptor; DAP12 ITAM mutant mice show 30–40-fold higher splenic viral titers and reduced IFN-γ production by hepatic NK cells. KARAP/DAP12 ITAM knockin mutant mice, viral titer assay, IFN-γ intracellular staining of NK cells Journal of Experimental Medicine High 11927627
2007 In CD4+CD28null T cells lacking DAP12, stimulatory KIR2DS2 signals selectively through JNK (not ERK); presence of DAP12 enables ERK phosphorylation, converting KIR2DS2 from a costimulatory to a fully stimulatory molecule capable of inducing cytotoxicity—demonstrated by KIR2DS2 transmembrane lysine mutant abolishing JNK activation. KIR2DS2 transmembrane domain mutagenesis, signaling assays (JNK, ERK phosphorylation), cytotoxicity assays, T cell clones with/without DAP12 Journal of Immunology High 15356118
2007 PU.1 directly binds to evolutionarily conserved PU.1 consensus sites in the proximal Dap12 promoter and is required for myeloid-specific Dap12 transcription; PU.1 knockdown reduces endogenous Dap12 expression and PU.1 re-expression in PU.1−/− progenitors induces Dap12 transcription. Reporter assays, site-directed mutagenesis, EMSA, chromatin immunoprecipitation, PU.1 RNAi, PU.1−/− progenitor reconstitution Journal of Leukocyte Biology High 17827340
2014 αvβ3 integrin occupancy induces DAP12 ITAM phosphorylation in osteoclasts; combined deletion of DAP12 and αvβ3 (but not DAP12 and β1) causes severe osteopetrosis, and OSCAR/FcRγ activation cannot rescue DAP12−/− osteoclasts lacking αvβ3 because Syk phosphorylation does not occur in this context. β3/DAP12 double-knockout mice, Syk phosphorylation assay, OSCAR activation rescue experiment, bone density analysis Journal of Cell Biology High 25547154
2017 TREM2/DAP12 signaling in microglia promotes proinflammatory cytokine secretion following spinal nerve injury; agonistic anti-TREM2 antibody induces proinflammatory cytokine expression and neuropathic pain in wild-type but not Dap12-deficient mice, placing TREM2 upstream of DAP12 in microglial pain signaling. DAP12 knockout mice, intrathecal TREM2 agonistic antibody, cytokine assays, behavioral pain assays Journal of Neuroscience High 27798193
2017 The TREM2/DAP12 complex suppresses LPS-induced microglial hyperactivation through the JNK signaling pathway; LPS downregulates TREM2 via JNK and NF-κB, and DAP12's anti-inflammatory role requires the presence of TREM2. siRNA knockdown, JNK inhibition, LPS stimulation cytokine assays, NF-κB reporter assays Frontiers in Aging Neuroscience Medium 28680398
2017 TYROBP (DAP12) deficiency in APP/PSEN1 mice preserves electrophysiological function and learning behavior; TYROBP deficiency prevents accumulation of complement C1q associated with cerebral amyloidosis and represses the induction of disease-associated microglia (DAM) genes including TREM2, C1q, and Clec7a. TYROBP knockout crossed to APP/PSEN1 AD mouse model, transcriptomics, electrophysiology, behavioral assays, complement staining Acta Neuropathologica / Molecular Psychiatry High 28612290 30283032
2023 Single-nucleus RNA-sequencing of brain specimens from DAP12-deficient NHD patients revealed a unique microglia signature of heightened RUNX1, STAT3, and TGF-β signaling pathways mediating wound-healing responses; this was associated with a wound-healing astrocyte signature, impaired myelination in oligodendrocytes, and vascular pericyte abnormalities—demonstrating that DAP12 normally attenuates microglial wound-healing pathways. Single-nucleus RNA-sequencing of human NHD patient brain specimens and DAP12-signaling-deficient mouse brain Nature Immunology High 36658241

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Injured sensory neuron-derived CSF1 induces microglial proliferation and DAP12-dependent pain. Nature neuroscience 445 26642091
1998 Association of DAP12 with activating CD94/NKG2C NK cell receptors. Immunity 429 9655483
2000 Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts. Nature genetics 370 10888890
2010 TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1. Science signaling 340 20484116
2003 Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice. The Journal of clinical investigation 284 12569157
2005 Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12. Nature immunology 266 15895090
2003 DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features. The Journal of experimental medicine 247 12925681
1998 Ly-49D and Ly-49H associate with mouse DAP12 and form activating receptors. Journal of immunology (Baltimore, Md. : 1950) 238 9647200
2018 Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases. Frontiers in cellular neuroscience 231 30127720
2007 Activating and inhibitory functions of DAP12. Nature reviews. Immunology 217 17220916
2018 Microglia and Aging: The Role of the TREM2-DAP12 and CX3CL1-CX3CR1 Axes. International journal of molecular sciences 216 29361745
2006 Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Nature cell biology 215 16715077
2015 DAP12-based activating chimeric antigen receptor for NK cell tumor immunotherapy. Journal of immunology (Baltimore, Md. : 1950) 205 25740942
2000 DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes in natural killer cells. The Journal of experimental medicine 190 11015446
2004 Impaired synaptic function in the microglial KARAP/DAP12-deficient mouse. The Journal of neuroscience : the official journal of the Society for Neuroscience 185 15601948
2005 The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2. Neurology 183 15883308
2007 The TREM-1/DAP12 pathway. Immunology letters 169 18192027
1999 Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells. Proceedings of the National Academy of Sciences of the United States of America 169 10449773
1998 DAP12-mediated signal transduction in natural killer cells. A dominant role for the Syk protein-tyrosine kinase. The Journal of biological chemistry 167 9830044
2000 The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function. Immunology today 162 11114420
2011 OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice. The Journal of clinical investigation 161 21841309
2001 Cloning and characterization of a novel mouse myeloid DAP12-associated receptor family. European journal of immunology 157 11241283
2012 The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway. Glycobiology 147 23035012
2004 Distribution and signaling of TREM2/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementia. The European journal of neuroscience 137 15548205
2003 NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases. Nature immunology 136 12740576
2005 TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 135 16418779
2016 TREM2/DAP12 Signal Elicits Proinflammatory Response in Microglia and Exacerbates Neuropathic Pain. The Journal of neuroscience : the official journal of the Society for Neuroscience 134 27798193
2000 Combined natural killer cell and dendritic cell functional deficiency in KARAP/DAP12 loss-of-function mutant mice. Immunity 134 11021533
2000 Cutting edge: signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells. Journal of immunology (Baltimore, Md. : 1950) 130 10604985
2004 Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy--PLOSL): a dementia associated with bone cystic lesions. From clinical to genetic and molecular aspects. Cellular and molecular neurobiology 125 15049507
1998 Gene structure, expression pattern, and biological activity of mouse killer cell activating receptor-associated protein (KARAP)/DAP-12. The Journal of biological chemistry 124 9852069
2022 Microglial TYROBP/DAP12 in Alzheimer's disease: Transduction of physiological and pathological signals across TREM2. Molecular neurodegeneration 119 36002854
2015 DAP12 Stabilizes the C-terminal Fragment of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) and Protects against LPS-induced Pro-inflammatory Response. The Journal of biological chemistry 116 25957402
2002 TREM-1, MDL-1, and DAP12 expression is associated with a mature stage of myeloid development. Molecular immunology 115 11922939
2005 KARAP/DAP12/TYROBP: three names and a multiplicity of biological functions. European journal of immunology 111 15884055
2004 A Structural basis for the association of DAP12 with mouse, but not human, NKG2D. Journal of immunology (Baltimore, Md. : 1950) 110 15294961
2005 Silencing human NKG2D, DAP10, and DAP12 reduces cytotoxicity of activated CD8+ T cells and NK cells. Journal of immunology (Baltimore, Md. : 1950) 106 16339517
2009 The expanding roles of ITAM adapters FcRgamma and DAP12 in myeloid cells. Immunological reviews 105 19909355
2003 The signaling adapter protein DAP12 regulates multinucleation during osteoclast development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 100 14969392
2008 Essential role of DAP12 signaling in macrophage programming into a fusion-competent state. Science signaling 97 18957693
2017 Deficiency of TYROBP, an adapter protein for TREM2 and CR3 receptors, is neuroprotective in a mouse model of early Alzheimer's pathology. Acta neuropathologica 95 28612290
2013 Siglec-15 regulates osteoclast differentiation by modulating RANKL-induced phosphatidylinositol 3-kinase/Akt and Erk pathways in association with signaling Adaptor DAP12. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 95 23677868
2005 Dap12 and Trem2, molecules involved in innate immunity and neurodegeneration, are co-expressed in the CNS. Neurobiology of disease 95 15686960
2015 Generation of Potent T-cell Immunotherapy for Cancer Using DAP12-Based, Multichain, Chimeric Immunoreceptors. Cancer immunology research 94 25941351
2003 High dose M-CSF partially rescues the Dap12-/- osteoclast phenotype. Journal of cellular biochemistry 92 14624447
2015 The TREM2-DAP12 signaling pathway in Nasu-Hakola disease: a molecular genetics perspective. Research and reports in biochemistry 89 26478868
2013 Structure, expression pattern and biological activity of molecular complex TREM-2/DAP12. Human immunology 85 23459077
2014 TYROBP in Alzheimer's disease. Molecular neurobiology 84 25052481
2000 Association of signal-regulatory proteins beta with KARAP/DAP-12. European journal of immunology 83 10940905
1999 Cutting edge: KAP10, a novel transmembrane adapter protein genetically linked to DAP12 but with unique signaling properties. Journal of immunology (Baltimore, Md. : 1950) 83 10528161
2008 Developmental regulation of TREM2 and DAP12 expression in the murine CNS: implications for Nasu-Hakola disease. Neurochemical research 82 18404378
2012 Siglec-15 protein regulates formation of functional osteoclasts in concert with DNAX-activating protein of 12 kDa (DAP12). The Journal of biological chemistry 81 22451653
2006 DAP12: an adapter protein with dual functionality. Immunological reviews 79 17100880
2002 Pivotal role of KARAP/DAP12 adaptor molecule in the natural killer cell-mediated resistance to murine cytomegalovirus infection. The Journal of experimental medicine 79 11927627
2004 NKp44 triggers NK cell activation through DAP12 association that is not influenced by a putative cytoplasmic inhibitory sequence. Journal of immunology (Baltimore, Md. : 1950) 78 14707061
2010 Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis. The Journal of experimental medicine 77 20212065
2017 TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway. Frontiers in aging neuroscience 69 28680398
2004 Stimulatory killer Ig-like receptors modulate T cell activation through DAP12-dependent and DAP12-independent mechanisms. Journal of immunology (Baltimore, Md. : 1950) 68 15356118
2017 Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network. Acta neuropathologica 67 28070672
2005 Brain and bone damage in KARAP/DAP12 loss-of-function mice correlate with alterations in microglia and osteoclast lineages. The American journal of pathology 67 15632019
2003 Selective activation of the c-Jun NH2-terminal protein kinase signaling pathway by stimulatory KIR in the absence of KARAP/DAP12 in CD4+ T cells. The Journal of experimental medicine 61 12591902
2018 Integrative approach to sporadic Alzheimer's disease: deficiency of TYROBP in cerebral Aβ amyloidosis mouse normalizes clinical phenotype and complement subnetwork molecular pathology without reducing Aβ burden. Molecular psychiatry 60 30283032
2013 A physical interaction between the adaptor proteins DOK3 and DAP12 is required to inhibit lipopolysaccharide signaling in macrophages. Science signaling 60 23962980
2009 Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis in cooperation with DAP12. Proceedings of the National Academy of Sciences of the United States of America 58 19251634
2004 Loss or mismatch of MHC class I is sufficient to trigger NK cell-mediated rejection of resting lymphocytes in vivo - role of KARAP/DAP12-dependent and -independent pathways. European journal of immunology 58 15162434
2020 T Cells Expressing NKG2D CAR with a DAP12 Signaling Domain Stimulate Lower Cytokine Production While Effective in Tumor Eradication. Molecular therapy : the journal of the American Society of Gene Therapy 56 32956627
2018 Integrative approach to sporadic Alzheimer's disease: deficiency of TYROBP in a tauopathy mouse model reduces C1q and normalizes clinical phenotype while increasing spread and state of phosphorylation of tau. Molecular psychiatry 55 30283031
2008 Increased TLR responses in dendritic cells lacking the ITAM-containing adapters DAP12 and FcRgamma. European journal of immunology 55 18081038
2007 Non-T cell activation linker (NTAL) negatively regulates TREM-1/DAP12-induced inflammatory cytokine production in myeloid cells. Journal of immunology (Baltimore, Md. : 1950) 53 17277102
2004 CD200 receptor family members represent novel DAP12-associated activating receptors on basophils and mast cells. The Journal of biological chemistry 51 15471863
2006 DAP12 signaling regulates plasmacytoid dendritic cell homeostasis and down-modulates their function during viral infection. Journal of immunology (Baltimore, Md. : 1950) 48 16920926
2004 IL-4 confers NK stimulatory capacity to murine dendritic cells: a signaling pathway involving KARAP/DAP12-triggering receptor expressed on myeloid cell 2 molecules. Journal of immunology (Baltimore, Md. : 1950) 48 15128777
1999 Induction of DAP12 phosphorylation, calcium mobilization, and cytokine secretion by Ly49H. Journal of leukocyte biology 46 10411005
1999 DAP12: a key accessory protein for relaying signals by natural killer cell receptors. The international journal of biochemistry & cell biology 45 10404635
2023 Human early-onset dementia caused by DAP12 deficiency reveals a unique signature of dysregulated microglia. Nature immunology 43 36658241
2011 Btk is a positive regulator in the TREM-1/DAP12 signaling pathway. Blood 43 21659545
2006 Regulation of Ly49D/DAP12 signal transduction by Src-family kinases and CD45. Journal of immunology (Baltimore, Md. : 1950) 42 16709819
2011 Involvement of the TREM-1/DAP12 pathway in the innate immune responses to Porphyromonas gingivalis. Molecular immunology 40 21967868
2021 TYROBP, TLR4 and ITGAM regulated macrophages polarization and immune checkpoints expression in osteosarcoma. Scientific reports 39 34588497
2014 Absence of Dap12 and the αvβ3 integrin causes severe osteopetrosis. The Journal of cell biology 39 25547154
2007 The zebrafish activating immune receptor Nitr9 signals via Dap12. Immunogenetics 39 17891481
1998 Assignment of the locus for PLO-SL, a frontal-lobe dementia with bone cysts, to 19q13. American journal of human genetics 39 9463329
2004 Differential regulation of DAP12 and molecules associated with DAP12 during host responses to mycobacterial infection. Infection and immunity 38 15102754
2022 Curcumin-Attenuated TREM-1/DAP12/NLRP3/Caspase-1/IL1B, TLR4/NF-κB Pathways, and Tau Hyperphosphorylation Induced by 1,2-Diacetyl Benzene: An in Vitro and in Silico Study. Neurotoxicity research 36 35781221
2020 Bilberry anthocyanins improve neuroinflammation and cognitive dysfunction in APP/PSEN1 mice via the CD33/TREM2/TYROBP signaling pathway in microglia. Food & function 35 32003387
2007 Critical negative regulation of type 1 T cell immunity and immunopathology by signaling adaptor DAP12 during intracellular infection. Journal of immunology (Baltimore, Md. : 1950) 35 17785840
2007 Dap12 expression in activated microglia from retinoschisin-deficient retina and its PU.1-dependent promoter regulation. Journal of leukocyte biology 35 17827340
2004 Human NKG2F is expressed and can associate with DAP12. Molecular immunology 35 15140575
2013 Pulmonary M. tuberculosis infection delays Th1 immunity via immunoadaptor DAP12-regulated IRAK-M and IL-10 expression in antigen-presenting cells. Mucosal immunology 34 24172845
2008 A critical role for DAP10 and DAP12 in CD8+ T cell-mediated tissue damage in large granular lymphocyte leukemia. Blood 34 19075187
2000 The role of the DAP12 signal in mouse myeloid differentiation. Journal of immunology (Baltimore, Md. : 1950) 34 11034384
2020 A Humanized Lym-1 CAR with Novel DAP10/DAP12 Signaling Domains Demonstrates Reduced Tonic Signaling and Increased Antitumor Activity in B-Cell Lymphoma Models. Clinical cancer research : an official journal of the American Association for Cancer Research 32 32273277
2015 Variable expression of microglial DAP12 and TREM2 genes in Nasu-Hakola disease. Neurogenetics 32 26001891
2019 Nonmuscle Myosin Heavy Chain IIA Recognizes Sialic Acids on Sialylated RNA Viruses To Suppress Proinflammatory Responses via the DAP12-Syk Pathway. mBio 31 31064828
2014 Human NKG2E is expressed and forms an intracytoplasmic complex with CD94 and DAP12. Journal of immunology (Baltimore, Md. : 1950) 28 24935923
2010 DAP12 is required for macrophage recruitment to the lung in response to cigarette smoke and chemotaxis toward CCL2. Journal of immunology (Baltimore, Md. : 1950) 28 20421649
2020 Siglecs that Associate with DAP12. Advances in experimental medicine and biology 27 32152949
2018 Integrated biology approach reveals molecular and pathological interactions among Alzheimer's Aβ42, Tau, TREM2, and TYROBP in Drosophila models. Genome medicine 26 29598827
2018 TLR4 Promotes and DAP12 Limits Obesity-Induced Osteoarthritis in Aged Female Mice. JBMR plus 26 31044181
2011 The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses. The Journal of experimental medicine 26 21727189