| 1999 |
DAP10 (HCST/KAP10) forms an activating immunoreceptor complex with NKG2D on NK and T cells, and the DAP10 cytoplasmic YINM (YxxM) motif recruits the p85 subunit of PI3-kinase, enabling NKG2D-dependent signal transduction in response to MICA. |
Biochemical co-immunoprecipitation, transfection assays, SH2 domain-binding assay |
Science |
High |
10426994
|
| 1999 |
KAP10 (DAP10/HCST) binds PI3-kinase upon phosphorylation of its cytoplasmic YINM motif, activating Akt, and also binds the adaptor protein Grb2; KAP10 is genetically encoded within ~100 bp of the DAP12 locus on chromosome 19. |
Molecular cloning, transfection, biochemical binding assays (PI3K and Grb2 co-precipitation), Akt activation assay |
Journal of Immunology |
High |
10528161
|
| 2000 |
DAP10 and DAP12 form distinct, specific receptor complexes in NK cells; the transmembrane regions of DAP10 and DAP12 are sufficient to confer specific association with their respective ligand-binding partners, and DAP10 signals via the PI3K (YxNM) pathway while DAP12 signals via Syk/ZAP70 through its ITAM motif. |
Transfectant cell lines, co-immunoprecipitation, mutant transmembrane domain constructs, cytotoxicity assays, cytokine production assays |
Journal of Experimental Medicine |
High |
11015446
|
| 2003 |
The YINM motif in the DAP10 cytoplasmic tail couples NKG2D stimulation to downstream activation of PI3K, Vav1, Rho family GTPases, and PLC, leading to NK cell killing in a Syk-family kinase-independent manner. |
Biochemical signaling assays, dominant-negative constructs, NK cytotoxicity assays |
Nature Immunology |
High |
12740575
|
| 2004 |
Vav1 is specifically required for DAP10-mediated NK cell cytotoxicity, whereas Vav2 and Vav3 are required for FcRγ- and DAP12-mediated cytotoxicity; genetic epistasis using mice lacking one, two, or all three Vav proteins places Vav1 specifically downstream of DAP10. |
Genetic epistasis using Vav1/Vav2/Vav3 knockout mice, NK cytotoxicity assays |
Journal of Experimental Medicine |
High |
15365099
|
| 2006 |
DAP10 recruits a Grb2-Vav1 intermediate complex as well as p85 PI3K; Grb2-Vav1 binding to DAP10 initiates tyrosine phosphorylation events, but full calcium release and cytotoxicity require both Grb2-Vav1 and p85 to bind DAP10 simultaneously. |
Co-immunoprecipitation, phosphorylation assays, calcium flux assays, NK cytotoxicity assays, dominant-negative constructs |
Nature Immunology |
High |
16582911
|
| 2006 |
Vav1 interacts with DAP10 YxNM motifs through Grb2 and is required for DAP10-induced NK cell cytoskeletal polarization (actin and microtubule networks), maturation of the cytolytic synapse, target cell lysis, and PI3K-dependent Akt signaling. |
Vav1/DAP12 double-knockout mice, co-immunoprecipitation, confocal microscopy of cytoskeletal polarization, cytotoxicity assays, Akt phosphorylation assay |
Journal of Immunology |
High |
16887996
|
| 2006 |
IL-21 down-regulates DAP10 (HCST) expression in human NK and CD8+ T cells by reducing DAP10 promoter activity, leading to decreased NKG2D surface expression and impaired NKG2D-mediated NK cell functions. |
DAP10 luciferase reporter assay, RT-PCR, flow cytometry, redirected lysis and degranulation assays |
Journal of Immunology |
Medium |
16424177
|
| 2009 |
DAP10 associates with the receptor MDL-1 in osteoclasts; MDL-1 associates with both DAP12 and DAP10 to form trimolecular MDL-1–DAP12/DAP10 complexes, and DAP10-deficient mice develop osteopetrosis with reduced osteoclast numbers, demonstrating DAP10's role in osteoclastogenesis and bone remodeling. |
DAP10-deficient mouse model, co-immunoprecipitation, osteoclast differentiation assays, bone histology |
PNAS |
High |
19251634
|
| 2009 |
Ly49H must associate with and signal via DAP10 (in addition to DAP12) for optimal NK cell function during mouse cytomegalovirus infection; DAP10-deficient Ly49H+ NK cells show impaired ERK1/2 activation, reduced IFN-γ production, and diminished MCMV control. |
DAP10-deficient mice, MCMV infection model, flow cytometry, ERK phosphorylation assay, IFN-γ production assay |
Journal of Experimental Medicine |
High |
19332875
|
| 2009 |
Upon NK cell activation by MICB-expressing target cells, the NKG2D/DAP10 complex undergoes lysosomal degradation; DAP10 traffics to secretory lysosomes and polarizes to the cytotoxic immune synapse, with ~50% of total NKG2D protein degraded coincident with synapse recruitment. |
Confocal microscopy, subcellular fractionation, flow cytometry, immunoblot in primary NK cells and NKL cell line |
Journal of Biological Chemistry |
Medium |
19329438
|
| 2010 |
DAP10 plays a key role in TREM2- and DAP12-dependent recruitment of PI3K to the signaling complex; SHIP1 inhibits TREM2/DAP12 signaling by binding DAP12 in an SH2 domain-dependent manner to prevent PI3K recruitment, while DAP10 enables PI3K activation downstream of TREM2-DAP12 in osteoclasts/macrophages. |
Co-immunoprecipitation, PI3K activity assay, calcium mobilization assay, actin reorganization assay, siRNA knockdown |
Science Signaling |
High |
20484116
|
| 2011 |
IL-2 up-regulates DAP10 protein expression largely post-transcriptionally and induces DAP10 glycosylation, which is required for DAP10 association with NKG2D and stabilization of NKG2D surface expression; TGF-β1 has an opposite and dominant effect by inhibiting RNA polymerase II association with the DAP10 promoter, decreasing DAP10 mRNA and protein and consequently NKG2D. |
Metabolic labeling, glycosylation inhibitor treatment, co-immunoprecipitation, ChIP (RNA Pol II), RT-PCR, flow cytometry, immunoblot |
Blood |
High |
21816829
|
| 2014 |
DAP10 associates with RAGE in human keratinocytes; RAGE-DAP10 heterodimer formation markedly enhances Akt activation, whereas RAGE-RAGE homomultimers activate caspase-8/apoptosis; functional blocking of DAP10 abrogates S100A8/A9-stimulated Akt phosphorylation and increases apoptosis. |
Co-immunoprecipitation, artificial oligomerization constructs, Akt phosphorylation assay, caspase-8 assay, DAP10 functional blocking antibody, cell viability assay |
Journal of Biological Chemistry |
Medium |
25002577
|
| 2015 |
Ligand-induced endocytosis of NKG2D-DAP10 complexes depends on ubiquitylation of DAP10 and is required for degradation of internalized complexes; this ubiquitin-dependent endocytosis is also required for ERK activation and NK cell effector functions (cytotoxic granule secretion and IFN-γ production). |
Biochemical ubiquitylation assays, endocytosis assays with ubiquitylation-deficient DAP10 mutants, confocal microscopy, ERK phosphorylation assay, degranulation and cytokine assays in human NK cells |
Science Signaling |
High |
26508790
|
| 2019 |
NKG2D-DAP10 signaling recruits the actin regulatory protein EVL to the NK cell cytotoxic synapse via the DAP10 binding site previously implicated in Grb2/Vav1 recruitment; EVL interacts with WASP and VASP and is required for F-actin generation, integrin-mediated adhesion, and NK cell cytotoxicity. |
Co-immunoprecipitation, confocal microscopy, siRNA knockdown, actin polymerization assays, adhesion and cytotoxicity assays |
Journal of Cell Science |
High |
31235500
|
| 2011 |
TGF-β1 down-regulates NKG2D and DAP10 expression on human NK cells, impairing NK cell cytotoxicity and IFN-γ production; anti-TGF-β1 antibodies restore NKG2D and DAP10 expression in vitro. |
In vitro treatment of primary NK cells with TGF-β1, flow cytometry, anti-TGF-β1 antibody rescue, cytotoxicity and IFN-γ assays |
PLoS Pathogens |
Medium |
22438812
|
| 2003 |
SIRPβ1 can associate with DAP10 in RBL-2H3 transfectants; however, engagement of SIRPβ1:DAP10 complexes alone does not induce serotonin release or TNF secretion (negative finding), but does co-stimulate RBL-2H3 effector function when sub-optimal FcεRI signaling is present. |
Transfectant cell lines, co-immunoprecipitation, serotonin release assay, TNF secretion assay, co-stimulation assay |
European Journal of Immunology |
Medium |
14635062
|
| 2009 |
DAP10 associates with Ly49H and Ly49D in primary NK cells in vivo, but this association has no significant impact on Ly49H-mediated control of murine cytomegalovirus infection under physiological conditions (DAP10's contribution to Ly49D/H function is minimal in vivo). |
DAP10-deficient mice, co-immunoprecipitation from primary NK cells, MCMV infection model, flow cytometry |
European Journal of Immunology |
Medium |
19247984
|
| 2011 |
In rat and mouse (but not human), CD94 — rather than NKG2C/E — associates with DAP12 and DAP10 through a transmembrane lysine residue unique to rodent CD94, enabling NK cell activation; this differs from the human system where NKG2C bears the DAP12-interacting residue. |
Biochemical analysis (co-immunoprecipitation), flow cytometry, mutant NKG2C constructs, redirected lysis assays with transfected NK cells |
Journal of Immunology |
Medium |
22084441
|
| 2007 |
DAP10-deficient mice become osteopetrotic with age, with reduced osteoclasts, demonstrating an essential role for DAP10 signaling in normal bone remodeling. |
DAP10-deficient mouse model, histological bone analysis, osteoclast counting |
PNAS |
High |
19251634
|
| 2007 |
DAP10 deficiency in mice leads to hyperactive NKT cell functions (increased cytokine production and cytotoxicity) and impaired CD4+CD25+ regulatory T cell activation, indicating that DAP10 signaling normally raises the activation threshold of autoreactive NKT cells and Tregs to maintain self-tolerance. |
DAP10-deficient mouse model, syngeneic tumor challenge, NKT cytotoxicity assays, Treg activation and cytokine assays |
Journal of Immunology |
Medium |
17785813
|
| 2025 |
ACLY deficiency in NK cells specifically reduces DAP10 and DAP12 transcript and protein levels through altered histone acetylation at the DAP10/DAP12 loci (as shown by epigenetic profiling), impairing activating receptor function; acetate supplementation restores DAP10/12 expression and receptor function, establishing that ACLY-generated cytosolic acetyl-CoA epigenetically regulates DAP10 expression. |
Inducible genetic KO mouse model (ACLY), RNA-seq, immunoblot, histone acetylation ChIP/epigenetic profiling, acetate rescue experiments, NK cytotoxicity and cytokine assays |
bioRxiv (preprint)preprint |
Medium |
bio_10.1101_2025.03.05.639198
|