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Gene Review

DOK1  -  docking protein 1, 62kDa (downstream of...

Homo sapiens

Synonyms: Docking protein 1, Downstream of tyrosine kinase 1, p62(dok), p62dok, pp62
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Disease relevance of DOK1


Psychiatry related information on DOK1


High impact information on DOK1


Chemical compound and disease context of DOK1


Biological context of DOK1


Anatomical context of DOK1

  • The data in this report show that both the DOK1 and the DOK2 adaptor proteins are constitutively expressed in the myelomonoblastic leukemia cell line, HL-60, and that expression of both proteins is induced by the chemotherapeutic differentiation causing agents, all-trans retinoic acid (atRA) and 1,25-dihydroxyvitamin D3 (VD3) [1].
  • However, p62(DOK1-/-) fibroblast knockout cells were found to have enhanced MAPK signaling and proliferation due to growth factors, suggesting negative regulatory capabilities for DOK1 [1].
  • We now find that IkappaB kinase beta (IKKbeta) associated with and phosphorylated Dok1 in human epithelial cells and B lymphocytes [14].
  • Taken together, Cas-L might be the bi-modal docking protein that assembles the signals through beta1-integrins and TCR/CD3, and participates in a variety of T-cell functions [15].
  • Dok1 inhibits MAP kinase activity, down-regulates cell proliferation and has a suppressive effect on cellular transformation and B-cell signalling pathways [2].

Associations of DOK1 with chemical compounds


Physical interactions of DOK1


Enzymatic interactions of DOK1


Regulatory relationships of DOK1


Other interactions of DOK1

  • We now report that SH2D1A associates with Dok1, a protein that interacts with Ras-GAP, Csk, and Nck [13].
  • Our structure-based mutational analyses define the molecular determinants for the two distinct Dok1 PTB domain/EGFR interactions and provide the structural understanding of the specific interactions between EGFR and PTB domains in the divergent Dok homologues [27].
  • A major substrate of Bcr-Abl was recently identified as the RasGAP-associated 62 kDa docking protein Dok1 [21].
  • The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells [21].
  • SNT/FRS2 is a lipid anchored docking protein that contains an amino-terminal myristylation signal, followed by a phosphotyrosine-binding (PTB) domain and a carboxy-terminal region with multiple tyrosine residues [33].

Analytical, diagnostic and therapeutic context of DOK1

  • We have screened the Dok1 gene for mutations from 46 individuals with B-CLL using heteroduplex analysis [34].
  • Confluent cultures of rat bone cells synthesize several forms of secreted phosphoprotein 1 (SPP-1, osteopontin), the major phosphorylated forms of which migrate at 55 and 44 kDa on 15% cross-linked SDS-PAGE gels and correspond to the transformation-associated proteins pp 69 and pp 62 [35].


  1. All-trans retinoic acid induces p62DOK1 and p56DOK2 expression which enhances induced differentiation and G0 arrest of HL-60 leukemia cells. Lamkin, T.J., Chin, V., Yen, A. Am. J. Hematol. (2006) [Pubmed]
  2. Germline mutations in Dok1 do not predispose to chronic lymphocytic leukemia. Sellick, G.S., Coleman, R.J., Talaban, R.V., Fleischmann, C., Rudd, M.F., Allinson, R., Catovsky, D., Houlston, R.S. Leuk. Res. (2005) [Pubmed]
  3. Protein kinase C-dependent tyrosine phosphorylation of p130cas in differentiating neuroblastoma cells. Fagerström, S., Påhlman, S., Nånberg, E. J. Biol. Chem. (1998) [Pubmed]
  4. Immunohistochemical study of the BCAR1/p130Cas protein in non-malignant and malignant human breast tissue. van der Flier, S., van der Kwast, T.H., Claassen, C.J., Timmermans, M., Brinkman, A., Henzen-Logmans, S.C., Foekens, J.A., Dorssers, L.C. Int. J. Biol. Markers (2001) [Pubmed]
  5. Diversity of HIV-1 Vpr interactions involves usage of the WXXF motif of host cell proteins. BouHamdan, M., Xue, Y., Baudat, Y., Hu, B., Sire, J., Pomerantz, R.J., Duan, L.X. J. Biol. Chem. (1998) [Pubmed]
  6. Neurons and plaques of Alzheimer's disease patients highly express the neuronal membrane docking protein p42IP4/centaurin alpha. Reiser, G., Bernstein, H.G. Neuroreport (2002) [Pubmed]
  7. Identification of the Abl- and rasGAP-associated 62 kDa protein as a docking protein, Dok. Yamanashi, Y., Baltimore, D. Cell (1997) [Pubmed]
  8. Secretory protein translocation across membranes-the role of the "docking protein'. Meyer, D.I., Krause, E., Dobberstein, B. Nature (1982) [Pubmed]
  9. Pax-5 (BSAP) recruits Ets proto-oncogene family proteins to form functional ternary complexes on a B-cell-specific promoter. Fitzsimmons, D., Hodsdon, W., Wheat, W., Maira, S.M., Wasylyk, B., Hagman, J. Genes Dev. (1996) [Pubmed]
  10. Gab1 and SHP-2 promote Ras/MAPK regulation of epidermal growth and differentiation. Cai, T., Nishida, K., Hirano, T., Khavari, P.A. J. Cell Biol. (2002) [Pubmed]
  11. The docking protein Gab2 is overexpressed and estrogen regulated in human breast cancer. Daly, R.J., Gu, H., Parmar, J., Malaney, S., Lyons, R.J., Kairouz, R., Head, D.R., Henshall, S.M., Neel, B.G., Sutherland, R.L. Oncogene (2002) [Pubmed]
  12. Signal characteristics of G protein-transactivated EGF receptor. Daub, H., Wallasch, C., Lankenau, A., Herrlich, A., Ullrich, A. EMBO J. (1997) [Pubmed]
  13. The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62dok (Dok1) and activates NF-kappa B. Sylla, B.S., Murphy, K., Cahir-McFarland, E., Lane, W.S., Mosialos, G., Kieff, E. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  14. IkappaB kinase beta phosphorylates Dok1 serines in response to TNF, IL-1, or gamma radiation. Lee, S., Andrieu, C., Saltel, F., Destaing, O., Auclair, J., Pouchkine, V., Michelon, J., Salaun, B., Kobayashi, R., Jurdic, P., Kieff, E.D., Sylla, B.S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  15. Beta 1-integrin-mediated cell signaling in T lymphocytes. Iwata, S., Ohashi, Y., Kamiguchi, K., Morimoto, C. J. Dermatol. Sci. (2000) [Pubmed]
  16. Tyrosine phosphorylation of p62(Dok) induced by cell adhesion and insulin: possible role in cell migration. Noguchi, T., Matozaki, T., Inagaki, K., Tsuda, M., Fukunaga, K., Kitamura, Y., Kitamura, T., Shii, K., Yamanashi, Y., Kasuga, M. EMBO J. (1999) [Pubmed]
  17. Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells. Manié, S.N., Beck, A.R., Astier, A., Law, S.F., Canty, T., Hirai, H., Druker, B.J., Avraham, H., Haghayeghi, N., Sattler, M., Salgia, R., Griffin, J.D., Golemis, E.A., Freedman, A.S. J. Biol. Chem. (1997) [Pubmed]
  18. Prostaglandin F2alpha stimulates tyrosine phosphorylation and mitogen-activated protein kinase in osteoblastic MC3T3-E1 cells via protein kinase C activation. Hakeda, Y., Shiokawa, M., Mano, H., Kameda, T., Raisz, L.G., Kumegawa, M. Endocrinology (1997) [Pubmed]
  19. A nuclear export signal and phosphorylation regulate Dok1 subcellular localization and functions. Niu, Y., Roy, F., Saltel, F., Andrieu-Soler, C., Dong, W., Chantegrel, A.L., Accardi, R., Thépot, A., Foiselle, N., Tommasino, M., Jurdic, P., Sylla, B.S. Mol. Cell. Biol. (2006) [Pubmed]
  20. The ADP/ATP carrier is the 32-kilodalton receptor for an NH2-terminally myristylated src peptide but not for pp60src polypeptide. Sigal, C.T., Resh, M.D. Mol. Cell. Biol. (1993) [Pubmed]
  21. The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells. Dunant, N.M., Wisniewski, D., Strife, A., Clarkson, B., Resh, M.D. Cell. Signal. (2000) [Pubmed]
  22. DOK1 mediates SHP-2 binding to the alphaVbeta3 integrin and thereby regulates insulin-like growth factor I signaling in cultured vascular smooth muscle cells. Ling, Y., Maile, L.A., Badley-Clarke, J., Clemmons, D.R. J. Biol. Chem. (2005) [Pubmed]
  23. Phosphotyrosine 1173 mediates binding of the protein-tyrosine phosphatase SHP-1 to the epidermal growth factor receptor and attenuation of receptor signaling. Keilhack, H., Tenev, T., Nyakatura, E., Godovac-Zimmermann, J., Nielsen, L., Seedorf, K., Böhmer, F.D. J. Biol. Chem. (1998) [Pubmed]
  24. Insulin receptor-mediated p62dok tyrosine phosphorylation at residues 362 and 398 plays distinct roles for binding GTPase-activating protein and Nck and is essential for inhibiting insulin-stimulated activation of Ras and Akt. Wick, M.J., Dong, L.Q., Hu, D., Langlais, P., Liu, F. J. Biol. Chem. (2001) [Pubmed]
  25. Suppression of protein kinase C is associated with inhibition of PYK2 tyrosine phosphorylation and enhancement of PYK2 interaction with Src in thrombin-activated platelets. Ohmori, T., Yatomi, Y., Asazuma, N., Satoh, K., Ozaki, Y. Thromb. Res. (1999) [Pubmed]
  26. Docking protein FRS2 links the protein tyrosine kinase RET and its oncogenic forms with the mitogen-activated protein kinase signaling cascade. Melillo, R.M., Santoro, M., Ong, S.H., Billaud, M., Fusco, A., Hadari, Y.R., Schlessinger, J., Lax, I. Mol. Cell. Biol. (2001) [Pubmed]
  27. Molecular basis of distinct interactions between Dok1 PTB domain and tyrosine-phosphorylated EGF receptor. Zhang, Y., Yan, Z., Farooq, A., Liu, X., Lu, C., Zhou, M.M., He, C. J. Mol. Biol. (2004) [Pubmed]
  28. Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL. Sakkab, D., Lewitzky, M., Posern, G., Schaeper, U., Sachs, M., Birchmeier, W., Feller, S.M. J. Biol. Chem. (2000) [Pubmed]
  29. IL-1beta suppresses prolonged Akt activation and expression of E2F-1 and cyclin A in breast cancer cells. Shen, W.H., Jackson, S.T., Broussard, S.R., McCusker, R.H., Strle, K., Freund, G.G., Johnson, R.W., Dantzer, R., Kelley, K.W. J. Immunol. (2004) [Pubmed]
  30. p62dok negatively regulates CD2 signaling in Jurkat cells. Némorin, J.G., Laporte, P., Bérubé, G., Duplay, P. J. Immunol. (2001) [Pubmed]
  31. Tyrosine phosphorylation of p62dok by p210bcr-abl inhibits RasGAP activity. Kashige, N., Carpino, N., Kobayashi, R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  32. Trans-activation of EphA4 and FGF receptors mediated by direct interactions between their cytoplasmic domains. Yokote, H., Fujita, K., Jing, X., Sawada, T., Liang, S., Yao, L., Yan, X., Zhang, Y., Schlessinger, J., Sakaguchi, K. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  33. Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction. Kurokawa, K., Iwashita, T., Murakami, H., Hayashi, H., Kawai, K., Takahashi, M. Oncogene (2001) [Pubmed]
  34. Frameshift mutation in the Dok1 gene in chronic lymphocytic leukemia. Lee, S., Roy, F., Galmarini, C.M., Accardi, R., Michelon, J., Viller, A., Cros, E., Dumontet, C., Sylla, B.S. Oncogene (2004) [Pubmed]
  35. Differential regulation of the 55 and 44 kDa forms of secreted phosphoprotein 1 (SPP-1, osteopontin) in normal and transformed rat bone cells by osteotropic hormones, growth factors and a tumor promoter. Kasugai, S., Zhang, Q., Overall, C.M., Wrana, J.L., Butler, W.T., Sodek, J. Bone and mineral. (1991) [Pubmed]
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