Gene Symbol: Dok3
Description: docking protein 3
Alias: AI450713, Dokl, docking protein 3, DOK-L, Dok-like protein, downstream of tyrosine kinase 3, p62(dok)-like protein, p62Dok-like protein
Species: mouse
Products:     Dok3

Top Publications

  1. Lemay S, Davidson D, Latour S, Veillette A. Dok-3, a novel adapter molecule involved in the negative regulation of immunoreceptor signaling. Mol Cell Biol. 2000;20:2743-54 pubmed
  2. Cong F, Yuan B, Goff S. Characterization of a novel member of the DOK family that binds and modulates Abl signaling. Mol Cell Biol. 1999;19:8314-25 pubmed
    A novel member of the p62(dok) family of proteins, termed DOKL, is described...
  3. Ng C, Xu S, Lam K. Dok-3 plays a nonredundant role in negative regulation of B-cell activation. Blood. 2007;110:259-66 pubmed
    ..Hence, we propose that Dok-3 plays a distinct and nonredundant role in the negative regulation of BCR signaling. ..
  4. Robson J, Davidson D, Veillette A. Inhibition of the Jun N-terminal protein kinase pathway by SHIP-1, a lipid phosphatase that interacts with the adaptor molecule Dok-3. Mol Cell Biol. 2004;24:2332-43 pubmed
    ..Together, these data elucidate the mechanism by which Dok-3 inhibits B-cell activation. Furthermore, they provide evidence that SHIP-1 can be a negative regulator of JNK signaling in B cells. ..
  5. Berger A, Niki M, Morotti A, Taylor B, Socci N, Viale A, et al. Identification of DOK genes as lung tumor suppressors. Nat Genet. 2010;42:216-23 pubmed publisher
    ..Here we identify the downstream of tyrosine kinase (Dok) family members Dok1, Dok2 and Dok3 as lung tumor suppressors...
  6. Honma M, Higuchi O, Shirakata M, Yasuda T, Shibuya H, Iemura S, et al. Dok-3 sequesters Grb2 and inhibits the Ras-Erk pathway downstream of protein-tyrosine kinases. Genes Cells. 2006;11:143-51 pubmed
    ..These findings indicate that Dok-3 sequesters Grb2 from Shc and inhibits the Ras-Erk pathway downstream of PTKs. ..
  7. Peng Q, Long C, Malhotra S, Humphrey M. A physical interaction between the adaptor proteins DOK3 and DAP12 is required to inhibit lipopolysaccharide signaling in macrophages. Sci Signal. 2013;6:ra72 pubmed publisher
    ..We show that inhibition of LPS responses by DAP12 is mediated by the adaptor protein DOK3 (downstream of kinase 3)...
  8. Liu N, Liu X, Li X, Duan K, Deng Y, Yu X, et al. DOK3 Degradation is Required for the Development of LPS-induced ARDS in Mice. Curr Gene Ther. 2016;16:256-262 pubmed publisher
    It has been reported that DOK3 protein negatively regulates LPS responses and endotoxin tolerance in mice. However, the role of DOK3 in the development of acute respiratory distress syndrome (ARDS) remains unknown...
  9. Kajikawa S, Taguchi Y, Hayata T, Ezura Y, Ueta R, Arimura S, et al. Dok-3 and Dok-1/-2 adaptors play distinctive roles in cell fusion and proliferation during osteoclastogenesis and cooperatively protect mice from osteopenia. Biochem Biophys Res Commun. 2018;498:967-974 pubmed publisher
    ..Together, our findings demonstrate that Dok-3 and Dok-1/-2 play distinctive but cooperative roles in osteoclastogenesis and protect mice from osteopenia, providing physiological and pathophysiological insight into bone homeostasis. ..

More Information


  1. Yogo K, Mizutamari M, Mishima K, Takenouchi H, Ishida Kitagawa N, Sasaki T, et al. Src homology 2 (SH2)-containing 5'-inositol phosphatase localizes to podosomes, and the SH2 domain is implicated in the attenuation of bone resorption in osteoclasts. Endocrinology. 2006;147:3307-17 pubmed
    ..These results demonstrate that c-Src enhances the translocation of SHIP to podosomes and regulates its function there through the SH2 domain, leading to an attenuation of bone resorption. ..
  2. Leung J, Yueh A, Appah F, Yuan B, De los Santos K, Goff S. Interaction of Moloney murine leukemia virus matrix protein with IQGAP. EMBO J. 2006;25:2155-66 pubmed
    ..Virus replication was potently inhibited by a C-terminal fragment of IQGAP1, and impaired by RNAi knockdown of IQGAP1 and 2. We suggest that the IQGAPs link the virus to the cytoskeleton for trafficking both into and out of the cell...
  3. Stork B, Neumann K, Goldbeck I, Alers S, Kahne T, Naumann M, et al. Subcellular localization of Grb2 by the adaptor protein Dok-3 restricts the intensity of Ca2+ signaling in B cells. EMBO J. 2007;26:1140-9 pubmed
    ..Hence, the Dok-3/Grb2 module is a membrane-associated signaling organizer, which orchestrates the interaction efficiency of Ca2+-mobilizing enzymes. ..
  4. Yang Y, Seed B. Site-specific gene targeting in mouse embryonic stem cells with intact bacterial artificial chromosomes. Nat Biotechnol. 2003;21:447-51 pubmed
    ..Correctly integrated clones were identified by a simple screening procedure based on chromosomal fluorescence in situ hybridization (FISH). To date, five mutant lines have been generated and bred to homozygosity by this approach. ..
  5. Grimm J, Sachs M, Britsch S, Di Cesare S, Schwarz Romond T, Alitalo K, et al. Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation. J Cell Biol. 2001;154:345-54 pubmed
    ..Thus, we have identified a subclass of p62dok proteins that are putative links with downstream effectors of c-Ret in neuronal differentiation. ..
  6. Schnyder T, Castello A, Feest C, Harwood N, Oellerich T, Urlaub H, et al. B cell receptor-mediated antigen gathering requires ubiquitin ligase Cbl and adaptors Grb2 and Dok-3 to recruit dynein to the signaling microcluster. Immunity. 2011;34:905-18 pubmed publisher
    ..Thus we identify a surprising but pivotal role for dynein and the microtubule network alongside Grb2, Dok-3, and Cbl in antigen gathering during B cell activation. ..
  7. Kim S, Lee K, Chin C, Ng S, Pereira N, Xu S, et al. DOK3 is required for IFN-? production by enabling TRAF3/TBK1 complex formation and IRF3 activation. J Immunol. 2014;193:840-8 pubmed publisher
    ..In this study, we elucidated a novel role for DOK3 in IFN-? production...
  8. Liu N, Tang B, Wei P, Sun W, Wang S, Peng Q. TRAF6-mediated degradation of DOK3 is required for production of IL-6 and TNFα in TLR9 signaling. Mol Immunol. 2015;68:699-705 pubmed publisher
    Our previous study showed that the downstream of kinase 3 (DOK3) is degraded during macrophage stimulation with CpG. However, the underlying mechanism and role in Toll-like receptor 9 (TLR9) signaling remains elusive...
  9. Mashima R, Honda K, Yang Y, Morita Y, Inoue A, Arimura S, et al. Mice lacking Dok-1, Dok-2, and Dok-3 succumb to aggressive histiocytic sarcoma. Lab Invest. 2010;90:1357-64 pubmed publisher
    ..Together, these findings indicate that Dok-1, Dok-2, and Dok-3 cooperatively suppress aggressive HS, and commend Dok-1(-/-)Dok-2(-/-)Dok-3(-/-) mice as a useful model for the study of this neoplasia. ..
  10. Peng Q, O Loughlin J, Humphrey M. DOK3 negatively regulates LPS responses and endotoxin tolerance. PLoS ONE. 2012;7:e39967 pubmed publisher
    ..We show here that DOK3 is a negative regulator of TLR signaling by limiting LPS-induced ERK activation and cytokine responses in ..
  11. Mashima R, Arimura S, Kajikawa S, Oda H, Nakae S, Yamanashi Y. Dok adaptors play anti-inflammatory roles in pulmonary homeostasis. Genes Cells. 2013;18:56-65 pubmed publisher
    ..In addition, Th2-type cytokine concentrations in BALF were increased in TKO mice. These findings provide strong evidence that Dok-1, Dok-2, and Dok-3 cooperatively play critical anti-inflammatory roles in lung homeostasis. ..
  12. Ou X, Xu S, Li Y, Lam K. Adaptor protein DOK3 promotes plasma cell differentiation by regulating the expression of programmed cell death 1 ligands. Proc Natl Acad Sci U S A. 2014;111:11431-6 pubmed publisher
    ..Although DOK3 is dispensable for early B-cell development, its role in plasma cell (PC) differentiation is unknown...