Affinage

DOK2

Docking protein 2 · UniProt O60496

Length
412 aa
Mass
45.4 kDa
Annotated
2026-06-09
34 papers in source corpus 21 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DOK2 is a tyrosine-phosphorylated adaptor protein that acts as a negative-feedback regulator of RAS–ERK and PI3K–AKT signaling downstream of receptor and non-receptor tyrosine kinases in hematopoietic and immune cells (PMID:9478921, PMID:15611294, PMID:15611295). Originally purified from BCR-ABL-expressing CML cells as a 56-kDa protein that directly binds p120 RasGAP, it carries an N-terminal PH domain, a PTB domain, and multiple tyrosine-phosphorylation sites (PMID:9478921). Combined loss of Dok-2 and its paralog Dok-1 in mice produces a CML-like myeloproliferative disease with hyperactivated ERK and Akt, establishing the pair as essential brakes on RAS/MAPK signaling (PMID:15611294, PMID:15611295). DOK2 is recruited to and phosphorylated downstream of diverse activating inputs—TLR4 and TLR2 in macrophages and glia (PMID:15699069, PMID:23659921), the TCR via a LAT/SHIP-1/Grb-2 complex that also restrains Akt and ZAP-70 (PMID:17043143, PMID:17329234), NK-activating receptors (PMID:24963146), and the inhibitory CD200 receptor, whose phosphorylated NPLY motif binds the DOK2 PTB domain to nucleate a DOK2–RasGAP inhibitory axis (PMID:19786546). Activation requires PH-domain binding to PtdIns5P for membrane recruitment and phosphorylation, and PTB-domain-mediated homo- and hetero-oligomerization with Dok-1 (PMID:16177091, PMID:19299694). In platelets DOK2 is phosphorylated by Lyn downstream of GPVI and integrin αIIbβ3, where it limits integrin adhesive function and thrombus growth (PMID:17092301, PMID:24385425). As a tumor suppressor, DOK2 forms a negative-feedback loop on mutant EGFR and, together with DUSP4, restrains MAPK-driven lung tumorigenesis (PMID:24255704, PMID:30475228). The HSV-1 tegument protein VP11/12 binds, phosphorylates, and triggers degradation of DOK2 as an immune-evasion strategy (PMID:28841444).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1998 High

    Identified the molecular identity of a prominent tyrosine-phosphorylated species in CML cells, establishing DOK2 as a multidomain adaptor that directly couples to the RAS regulator RasGAP.

    Evidence Protein purification, cDNA cloning, domain analysis, and RasGAP binding assay from BCR-ABL CML cells

    PMID:9478921

    Open questions at the time
    • Did not establish a cellular phenotype for DOK2 loss
    • Tyrosine kinase(s) driving phosphorylation not defined
    • Functional consequence of RasGAP binding untested
  2. 2004 High

    Genetic epistasis showed DOK2 and DOK1 are jointly required to suppress RAS/MAPK and Akt signaling in hematopoietic cells, defining their tumor-suppressive negative-feedback role.

    Evidence Single and double knockout mice with hematopoietic and Ras/MAPK activation analysis

    PMID:15611294 PMID:15611295

    Open questions at the time
    • Functional redundancy obscures Dok-2-specific roles
    • Direct molecular targets within the pathway not resolved here
    • Mechanism of ERK/Akt suppression not dissected
  3. 2004 Medium

    Linked DOK2 to a specific upstream kinase by showing it associates with and feedback-inhibits Tec in T cells, extending its negative regulation beyond receptor tyrosine kinases.

    Evidence Co-immunoprecipitation with Tec and Ras-pathway assays upon Dok overexpression in T cells

    PMID:14647425

    Open questions at the time
    • Single lab, no genetic confirmation
    • Direct vs indirect Tec association not distinguished
    • Physiological setting where this loop dominates unclear
  4. 2005 High

    Established DOK2 as a phosphorylation-dependent negative regulator of TLR4-driven ERK signaling and TNF-α production in macrophages, extending its role into innate immunity.

    Evidence Dok-1/Dok-2 knockout macrophages with gain-of-function and a Tyr/Phe mutant, ERK/NF-κB and cytokine readouts

    PMID:15699069

    Open questions at the time
    • Pathway selectivity for ERK over NF-κB mechanistically unexplained
    • Adaptor connecting DOK2 to TLR4 not identified
    • In vivo inflammatory consequence not tested here
  5. 2005 Medium

    Defined the PTB domain and Tyr139 as required for phosphotyrosine-dependent oligomerization, linking DOK2 self/cross-association to its phosphorylation and inhibitory function.

    Evidence Co-IP, PTB and Tyr139Phe mutants, ERK and NFAT reporter assays in Jurkat cells

    PMID:16177091

    Open questions at the time
    • Structural basis of oligomerization not defined
    • Single-lab overexpression system
    • Whether oligomerization occurs at endogenous levels untested
  6. 2006 High

    Placed DOK2 within a LAT-anchored, SHIP-1-dependent complex that restrains early TCR signaling at the level of Akt and ZAP-70, defining a membrane-proximal negative feedback loop.

    Evidence Reciprocal co-IP, LAT/SHIP-1 siRNA, phospho-Akt and phospho-Zap-70 analysis in T cells

    PMID:17043143

    Open questions at the time
    • Stoichiometry and order of complex assembly unresolved
    • Direct vs scaffolded LAT interaction unclear
    • How SHIP-1 favors DOK2 recruitment mechanistically undefined
  7. 2006 Medium

    Demonstrated DOK2-specific (Dok-1-independent) phosphorylation downstream of GPVI and integrin αIIbβ3 in platelets, with physical association to the integrin, implicating it in outside-in signaling.

    Evidence Differential phosphorylation, Src inhibitors, calcium chelation, and co-IP in mouse platelets

    PMID:17092301

    Open questions at the time
    • Direct vs indirect integrin association not resolved
    • Functional consequence not yet established here
    • Responsible Src-family kinase not identified at this stage
  8. 2007 High

    Revealed a non-canonical inhibitory mechanism: DOK2 suppresses ZAP-70 activation independent of its C-terminal SH2-target (RasGAP-recruiting) motifs, distinguishing it from the classical adaptor function.

    Evidence Dok-1/Dok-2 knockout mice, forced expression with C-terminal deletion mutants, phospho-ZAP-70 and proliferation assays

    PMID:17329234

    Open questions at the time
    • Domain mediating ZAP-70 inhibition not pinpointed
    • Direct vs indirect ZAP-70 regulation unresolved
    • Molecular intermediary not identified
  9. 2009 High

    Quantitatively defined CD200R as a direct DOK2 receptor through phospho-NPLY/PTB binding and showed the DOK2–RasGAP axis is essential and Dok-2-selective for CD200R-mediated inhibition of myeloid cells.

    Evidence Phosphopeptide affinity measurement, co-IP, siRNA of Dok-2/Dok-1/RasGAP/SHIP, and NPLY receptor mutants in U937 cells

    PMID:19786546

    Open questions at the time
    • Structure of the CD200R–PTB complex not solved
    • Why Dok-2 outcompetes Dok-1 mechanistically unclear beyond affinity
    • Downstream effectors of RasGAP not enumerated
  10. 2009 Medium

    Connected lipid binding to activation by showing the PH domain binds PtdIns5P and that PtdIns5P is required for DOK2 tyrosine phosphorylation and inhibitory function in T cells.

    Evidence In vitro PH–PtdIns5P binding, in vivo PtdIns5P modulation, and PH-deletion mutant phosphotyrosine analysis

    PMID:19299694

    Open questions at the time
    • In vivo membrane localization not directly imaged
    • Single lab
    • Enzymatic source of PtdIns5P pool not defined
  11. 2012 Medium

    Extended the CD200R–DOK2 inhibitory axis to the CNS, showing DOK2 phosphorylation is required for CD200R-mediated suppression of microglial inflammatory activation.

    Evidence siRNA knockdown of Dok2 in glia with CD200Fc stimulation and cytokine/activation-marker readouts

    PMID:22642833

    Open questions at the time
    • Single-lab knockdown without genetic confirmation
    • Downstream signaling in microglia not mapped
    • In vivo neuroinflammatory relevance untested
  12. 2013 High

    Established DOK2 as a tumor suppressor in EGFR-mutant lung cancer through a negative-feedback loop on mutant EGFR, with oncogene specificity (EGFR but not KRAS).

    Evidence Co-IP of DOK2 with EGFR, RAS activation assays, and EGFR-mutant Dok2-knockout mouse models

    PMID:24255704

    Open questions at the time
    • Direct vs adaptor-mediated EGFR binding unresolved
    • Why KRAS-mutant tumors are unaffected not explained
    • Human tumor data correlation not addressed here
  13. 2013 Medium

    Implicated DOK2 in chemotherapy response by showing its loss reduces carboplatin-induced apoptosis and anoikis in ovarian cancer cells.

    Evidence siRNA/shRNA knockdown in ovarian cancer lines with carboplatin resistance and apoptosis/anoikis assays

    PMID:23684582

    Open questions at the time
    • Mechanism linking DOK2 to apoptosis not defined
    • Single-lab cell-line study
    • In vivo therapeutic relevance untested
  14. 2013 Medium

    Showed TLR2-induced DOK2 phosphorylation and revealed cell-type-specific division of labor between Dok-1 and Dok-2 in glial inflammatory signaling.

    Evidence siRNA knockdown of Dok1 and Dok2 in primary astrocytes and microglia with ERK/NF-κB and IL-6 readouts

    PMID:23659921

    Open questions at the time
    • Basis of cell-type specificity unexplained
    • Direct TLR2 coupling not demonstrated
    • Single-lab knockdown without rescue
  15. 2014 High

    Identified Lyn as the DOK2 kinase in platelets and demonstrated that DOK2 loss enhances integrin αIIbβ3 adhesion and accelerates thrombus formation in vivo, establishing a hemostatic regulatory role.

    Evidence Dok-2 knockout mice, kinase identification, calcium and PI(3,4)P2 measurements, flow-adhesion and in vivo thrombosis assays

    PMID:24385425

    Open questions at the time
    • Direct DOK2 substrates/effectors in platelets not defined
    • Link between PI(3,4)P2 accumulation and adhesion mechanistic detail incomplete
    • Single lab
  16. 2014 High

    Established DOK2 (with Dok-1) as a negative regulator of NK-cell activation and maturation downstream of activating receptors.

    Evidence Overexpression in human NK cells and Dok1/Dok2 knockout mice with maturation and IFN-γ readouts

    PMID:24963146

    Open questions at the time
    • Specific activating receptors coupled to DOK2 not enumerated
    • Dok-2-specific vs redundant contributions not separated
    • Molecular target in NK cells unresolved
  17. 2014 Low

    Reported an unexpected nuclear, transcriptional-repressor role: DOK2 binds the Klf1 promoter and represses its transcription in erythroleukemia cells.

    Evidence Immunocytochemistry, ChIP at the Klf1 promoter, and siRNA knockdown with RT-PCR in a single cell line

    PMID:25075100

    Open questions at the time
    • Nuclear localization unexpected and not independently confirmed
    • Single cell line without replication
    • No demonstrated DNA-binding domain or direct binding mechanism
  18. 2017 Medium

    Defined a viral immune-evasion mechanism in which HSV-1 VP11/12 binds, phosphorylates, and targets DOK2 for degradation, requiring VP11/12 SFK- and SHC-binding motifs.

    Evidence Co-IP of Dok-2 with VP11/12, VP11/12 binding-motif mutants, and phosphorylation/protein-level analysis upon HSV-1 infection

    PMID:28841444

    Open questions at the time
    • Degradation machinery (e.g., proteasome/ubiquitin) not identified
    • Functional immune consequence of DOK2 loss in infection untested
    • Single lab
  19. 2018 High

    Demonstrated synergistic tumor suppression by showing co-deletion of DOK2 and DUSP4 drives MAPK activation and lung tumorigenesis, reversible by their restoration.

    Evidence Compound heterozygous mouse model, MAPK assays, and DOK2/DUSP4 restoration with proliferation assays in cancer cell lines

    PMID:30475228

    Open questions at the time
    • Mechanistic interplay between DOK2 and DUSP4 nodes not fully resolved
    • Whether the two act on the same or parallel MAPK steps unclear
    • Direct binding partners in this context not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DOK2 selectively inhibits ERK versus NF-κB, the structural basis of its PTB/PH-mediated receptor and lipid recognition, and the validity of its proposed nuclear transcriptional role remain unresolved.
  • No structural model of PTB–phosphoreceptor or PH–PtdIns5P complexes
  • Nuclear/transcriptional function rests on a single low-confidence study
  • Pathway-selectivity mechanism (ERK-specific suppression) undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-109582 Hemostasis 2 R-HSA-1643685 Disease 2
Partners
CD200R1DOK1EGFRGRB2INPP5DITGB3LATRASA1
Complex memberships
LAT signaling complex (with SHIP-1 and Grb-2)

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 DOK2 (p56dok-2) was purified from BCR-ABL-expressing CML cells as a 56-kDa tyrosine-phosphorylated protein. It encodes a 412-amino acid protein with an N-terminal pleckstrin homology (PH) domain, 13 potential tyrosine phosphorylation sites, six PXXP motifs, and directly binds to p120(RasGAP). Protein purification, cDNA cloning, domain analysis, RasGAP binding assay The Journal of biological chemistry High 9478921
2003 In human platelets, DOK2 undergoes tyrosine phosphorylation upon stimulation by thrombin receptor activating peptide (TRAP), collagen receptor GPVI signaling, and outside-in signaling through integrin αIIbβ3. 2D gel electrophoresis, LC-MS/MS proteomics, phosphotyrosine analysis Blood Medium 14645010
2004 Dok-1 and Dok-2 double-knockout mice develop spontaneous CML-like myeloproliferative disease with enhanced Ras/MAPK (ERK) and Akt activation, demonstrating that both proteins are required for negative regulation of RAS/MAP kinase signaling downstream of tyrosine kinases in hematopoietic cells. Single knockouts show normal hematopoiesis. Single and double knockout mouse generation, hematopoietic analysis, Ras/MAPK activation assays The Journal of experimental medicine High 15611294 15611295
2005 LPS rapidly induces tyrosine phosphorylation of Dok-1 and Dok-2 in macrophages downstream of TLR4. Knockout of either protein leads to elevated ERK (but not NF-κB or other MAP kinases) activation and hyperproduction of TNF-α, while forced expression of Dok-2 (but not a Tyr/Phe substitution mutant) inhibits LPS-induced ERK activation, establishing Dok-2 as a negative regulator of TLR4-dependent Ras-ERK signaling requiring its tyrosine phosphorylation. Dok-1/Dok-2 knockout macrophages, forced expression with Tyr/Phe mutant, ERK/NF-κB activity assays, cytokine measurement The Journal of experimental medicine High 15699069
2005 The PTB domain of Dok-2 mediates phosphotyrosine-dependent homotypic (Dok-2/Dok-2) and heterotypic (Dok-1/Dok-2) oligomerization. Mutation of either the PTB domain or Tyr139 of Dok-2 abrogates CD2-induced Dok-2 phosphorylation and its ability to inhibit CD2-induced ERK1/2 and NFAT activation, indicating PTB-mediated oligomerization is required for Dok-2 phosphorylation and inhibitory function. Co-immunoprecipitation, PTB domain mutant and Tyr139Phe mutant overexpression, ERK and NFAT reporter assays in Jurkat cells Journal of immunology Medium 16177091
2006 After TCR stimulation, Dok-2 (and Dok-1) form a multimolecular complex including SHIP-1 and Grb-2 that interacts with the membrane scaffold LAT. SHIP-1 favors recruitment of Dok-2 to LAT. Knockdown of Dok-2 (and Dok-1) reveals their negative regulation of Akt and Zap-70 activation, placing them in a LAT-dependent negative feedback loop that attenuates early TCR signaling. Co-immunoprecipitation, LAT/SHIP-1 siRNA knockdown, phospho-Akt and phospho-Zap-70 analysis in T cells The Journal of experimental medicine High 17043143
2006 In platelets, Dok-2 phosphorylation is downstream of GPVI and integrin αIIbβ3 (but Dok-1 is not); Dok-2 phosphorylation is inhibited by Src kinase inhibitors and intracellular calcium chelation; Dok-2 coimmunoprecipitates with integrin αIIbβ3, suggesting a physical and functional interaction in integrin outside-in signaling. Differential phosphorylation analysis, Src kinase inhibitors, calcium chelation, co-immunoprecipitation in mouse platelets Journal of thrombosis and haemostasis Medium 17092301
2007 Dok-1 and Dok-2 negatively regulate ZAP-70 activation upon TCR stimulation. Mice lacking both proteins show elevated ZAP-70 activation, proliferation, and cytokine production in T cells. Importantly, forced expression of Dok-1 or Dok-2 in CD3+CD4+ T cells inhibited ZAP-70 activation, and this effect was independent of the C-terminal SH2 target motifs, indicating a novel mechanism distinct from the classical RasGAP-recruiting adaptor function. Dok-1/Dok-2 knockout mice, forced expression in T cell clones, phospho-ZAP-70 and proliferation assays, C-terminal deletion mutant analysis International immunology High 17329234
2009 The CD200 receptor (CD200R) directly recruits Dok-2 via its phosphorylated NPLY (PTB domain-binding) motif with ~1 µM affinity (10-fold higher than Dok-1). Dok-2 is then phosphorylated and recruits RasGAP. siRNA knockdown of Dok-2 and RasGAP abolished CD200R-mediated inhibition of human myeloid cells, while Dok-1 and SHIP knockdown had no effect, establishing a Dok-2–RasGAP axis as essential for CD200R signaling. Phosphopeptide binding affinity measurement, co-immunoprecipitation, siRNA knockdown of Dok-2/Dok-1/RasGAP/SHIP in U937 cells, NPLY mutant receptor constructs Journal of immunology High 19786546
2009 The PH domains of Dok-1 and Dok-2 bind phosphatidylinositol 5-phosphate (PtdIns5P) in vitro, and PtdIns5P production upon TCR triggering correlates with and is required for Dok tyrosine phosphorylation in vivo. PH domain deletion prevents tyrosine phosphorylation and negative signaling function, linking lipid-PH domain interaction to Dok-2 activation. In vitro lipid-binding assay (PH domain–PtdIns5P), PtdIns5P manipulation in T cells, PH domain deletion mutant analysis, phosphotyrosine detection Journal of immunology Medium 19299694
2012 Dok2 phosphorylation is required for the inhibitory effect of CD200R activation (via CD200Fc) on microglial activation and inflammatory cytokine (IL-1β, TNFα) production; siRNA knockdown of Dok2 abrogates the anti-inflammatory effects of CD200Fc in cultured glia. siRNA knockdown of Dok2 in glial cells, CD200Fc stimulation, cytokine measurement, microglial activation marker analysis Journal of neuroinflammation Medium 22642833
2013 DOK2 participates in a negative feedback loop downstream of mutant EGFR: mutated EGFR leads to recruitment of DOK2 to EGFR and DOK2-mediated inhibition of downstream RAS activation. Loss of Dok2 in mice accelerates EGFR-mutant (but not Kras-mutant) lung tumorigenesis. Co-immunoprecipitation of DOK2 with EGFR, RAS activation assays, genetically engineered mouse models with EGFR mutation and Dok2 knockout PloS one High 24255704
2013 Loss of DOK2 decreases apoptosis in response to carboplatin treatment and reduces anoikis in ovarian cancer cells, linking DOK2 function to pro-apoptotic signaling downstream of platinum-induced damage. siRNA/shRNA knockdown of DOK2 in ovarian cancer cell lines, carboplatin resistance assay, apoptosis and anoikis measurement Gynecologic oncology Medium 23684582
2013 TLR2 activation induces tyrosine phosphorylation of Dok-1 and Dok-2 in both astrocytes and microglia. In astrocytes, siRNA knockdown of both Dok1 and Dok2 elevates TLR2-induced ERK, NF-κB activation, and IL-6 production. In microglia, Dok1 knockdown (but not Dok2 knockdown) affects NF-κB activation and IL-6, revealing cell-type-specific differential roles. siRNA knockdown of Dok1 and Dok2 in primary glia, phosphotyrosine western blotting, ERK/NF-κB activation assays, IL-6 measurement Molecular and cellular neurosciences Medium 23659921
2014 Dok-2 in platelets is primarily phosphorylated by Lyn kinase. Dok-2 deficiency leads to dysregulated integrin αIIbβ3-dependent cytosolic calcium flux and PI(3,4)P2 accumulation. Dok-2(-/-) platelets exhibit shear-dependent increases in integrin αIIbβ3 adhesive function affecting membrane tether regulation, resulting in enhanced platelet aggregate formation and accelerated thrombus growth in vivo. Dok-2 knockout mice, Lyn kinase identification, calcium flux assay, PI(3,4)P2 measurement, platelet adhesion under flow, in vivo thrombosis model The Journal of biological chemistry High 24385425
2014 Dok-1 and Dok-2 are tyrosine phosphorylated upon NK cell activation. Overexpression of Dok proteins in human NK cells reduces activation by NK-activating receptors. Dok1/Dok2 gene ablation in mice causes NK cell maturation defects and increased IFN-γ production, establishing their role in a negative feedback loop downstream of NK-activating receptors. Overexpression in human NK cells, Dok1/Dok2 knockout mice, NK cell maturation and IFN-γ production assays The EMBO journal High 24963146
2014 Dok2 protein localizes to the nucleus of erythroleukemia cells and binds directly to the promoter region of the Klf1 gene, repressing Klf1 transcription; Dok2 knockdown leads to increased Klf1 mRNA expression. Immunocytochemistry for nuclear localization, chromatin immunoprecipitation (ChIP) of Dok2 at Klf1 promoter, siRNA knockdown with RT-PCR Anticancer research Low 25075100
2017 HSV-1 infection of T cells induces tyrosine phosphorylation of Dok-2 and its selective degradation. Dok-2 physically interacts with the viral tegument protein VP11/12, and this interaction requires the Src Family Kinase-binding motifs and SHC-binding motif of VP11/12. Both the phosphorylation and degradation of Dok-2 are dependent on VP11/12. Co-immunoprecipitation of Dok-2 with VP11/12, VP11/12 binding motif mutants, western blotting for phosphorylation and protein levels upon HSV-1 infection Virology Medium 28841444
2018 Compound heterozygous deletion of Dok2 and Dusp4 (co-deleted in ~50% of human lung adenocarcinomas) in mice causes lung tumorigenesis with short latency. Their co-deletion synergistically activates MAPK signaling and promotes cell proliferation; restoration of DOK2 and DUSP4 in lung cancer cells suppresses MAPK activation and cell proliferation. Compound heterozygous mouse model, MAPK activation assays, DOK2/DUSP4 restoration in cancer cell lines, cell proliferation assays The Journal of clinical investigation High 30475228
2004 Dok-1 and Dok-2 are major tyrosine-phosphorylated proteins associated with the Tec tyrosine kinase in T cells. Dok-1 or Dok-2 expression provides negative feedback regulation of Tec by downregulating its tyrosine phosphorylation and downstream Ras pathway signaling. Co-immunoprecipitation of Dok-1/Dok-2 with Tec, Tec phosphorylation and Ras pathway activity assays upon Dok overexpression in T cells Oncogene Medium 14647425

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Differential proteome analysis of TRAP-activated platelets: involvement of DOK-2 and phosphorylation of RGS proteins. Blood 142 14645010
2009 Essential roles for Dok2 and RasGAP in CD200 receptor-mediated regulation of human myeloid cells. Journal of immunology (Baltimore, Md. : 1950) 125 19786546
1998 Molecular cloning and characterization of p56dok-2 defines a new family of RasGAP-binding proteins. The Journal of biological chemistry 112 9478921
2006 T cell receptor for antigen induces linker for activation of T cell-dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2. The Journal of experimental medicine 92 17043143
2004 Role of Dok-1 and Dok-2 in myeloid homeostasis and suppression of leukemia. The Journal of experimental medicine 86 15611294
2007 Dok-1 and Dok-2 are negative regulators of T cell receptor signaling. International immunology 76 17329234
2005 Dok-1 and Dok-2 are negative regulators of lipopolysaccharide-induced signaling. The Journal of experimental medicine 74 15699069
2004 Role of Dok-1 and Dok-2 in leukemia suppression. The Journal of experimental medicine 74 15611295
2000 p56(dok-2) as a cytokine-inducible inhibitor of cell proliferation and signal transduction. The EMBO journal 62 11013214
2009 Cutting edge: Dok-1 and Dok-2 adaptor molecules are regulated by phosphatidylinositol 5-phosphate production in T cells. Journal of immunology (Baltimore, Md. : 1950) 52 19299694
2012 Dok2 mediates the CD200Fc attenuation of Aβ-induced changes in glia. Journal of neuroinflammation 46 22642833
2013 Loss of DOK2 induces carboplatin resistance in ovarian cancer via suppression of apoptosis. Gynecologic oncology 38 23684582
2014 Dok1 and Dok2 proteins regulate natural killer cell development and function. The EMBO journal 35 24963146
2004 Functional interaction of RasGAP-binding proteins Dok-1 and Dok-2 with the Tec protein tyrosine kinase. Oncogene 31 14647425
2013 Differential role of Dok1 and Dok2 in TLR2-induced inflammatory signaling in glia. Molecular and cellular neurosciences 28 23659921
2018 Compound haploinsufficiency of Dok2 and Dusp4 promotes lung tumorigenesis. The Journal of clinical investigation 25 30475228
2019 Long noncoding RNA AK089579 inhibits epithelial-to-mesenchymal transition of peritoneal mesothelial cells by competitively binding to microRNA-296-3p via DOK2 in peritoneal fibrosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 30652956
2016 Dok1 and Dok2 Proteins Regulate Cell Cycle in Hematopoietic Stem and Progenitor Cells. Journal of immunology (Baltimore, Md. : 1950) 17 27183638
2005 Phosphotyrosine binding-mediated oligomerization of downstream of tyrosine kinase (Dok)-1 and Dok-2 is involved in CD2-induced Dok phosphorylation. Journal of immunology (Baltimore, Md. : 1950) 17 16177091
2006 Differential regulation of adapter proteins Dok2 and Dok1 in platelets, leading to an association of Dok2 with integrin alphaIIbbeta3. Journal of thrombosis and haemostasis : JTH 16 17092301
2021 Introduction to DOK2 and its potential role in cancer. Physiological research 14 34505522
2017 Co-expression and significance of Dok2 and Ras p21 protein activator 1 in breast cancer. Oncology letters 13 29098030
2013 DOK2 inhibits EGFR-mutated lung adenocarcinoma. PloS one 13 24255704
2014 Dok-2 adaptor protein regulates the shear-dependent adhesive function of platelet integrin αIIbβ3 in mice. The Journal of biological chemistry 12 24385425
2014 Expression and significance of DOK2 in colorectal cancer. Oncology letters 12 25435967
2017 Dok-1 and Dok-2 Are Required To Maintain Herpes Simplex Virus 1-Specific CD8+ T Cells in a Murine Model of Ocular Infection. Journal of virology 9 28490594
2017 Herpes simplex virus 1 infection of T cells causes VP11/12-dependent phosphorylation and degradation of the cellular protein Dok-2. Virology 8 28841444
2016 Dok-1 and Dok-2 Regulate the Formation of Memory CD8+ T Cells. Journal of immunology (Baltimore, Md. : 1950) 8 27664281
2011 Dok-1 and Dok-2 deficiency induces osteopenia via activation of osteoclasts. Journal of cellular physiology 8 21732353
2025 Bioinformatics-based identification of CTSS, DOK2, and ENTPD1 as potential blood biomarkers of schizophrenia. BMC psychiatry 5 39972407
2016 Loss of Dok-1 and Dok-2 in mice causes severe experimental colitis accompanied by reduced expression of IL-17A and IL-22. Biochemical and biophysical research communications 5 27450811
2025 Identification of anti-DOK2 antibodies in patients with autoimmune hepatitis via a human protein microarray. Hepatology communications 4 40982233
2024 DOK1 and DOK2 regulate CD8 T cell signaling and memory formation without affecting tumor cell killing. Scientific reports 4 38956389
2014 Dok2 likely down-regulates Klf1 in mouse erythroleukemia cells. Anticancer research 2 25075100

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