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Gene Review

DOCK1  -  dedicator of cytokinesis 1

Homo sapiens

Synonyms: 180 kDa protein downstream of CRK, DOCK180, Dedicator of cytokinesis protein 1, ced5
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Disease relevance of DOCK1


High impact information on DOCK1


Biological context of DOCK1


Anatomical context of DOCK1

  • Whereas wild-type DOCK180 accumulated diffusely in the cytoplasm and did not have any effect on cell morphology, farnesylated DOCK180 was localized on the cytoplasmic membrane and changed spindle 3T3 cells to flat, polygonal cells [13].
  • Internalization is dependent upon signalling through the beta5 cytoplasmic tail, and engagement of the alphavbeta5 heterodimer results in recruitment of the p130cas-CrkII-Dock180 molecular complex, which in turn triggers Rac1 activation and phagosome formation [14].
  • Interestingly, deletion mutants of ELMO1 missing their first 531 or first 330 amino acids that can still bind and cooperate with Dock180 in Rac activation failed to promote migration, which correlated with the inability to localize to lamellipodia [15].
  • DOCK2 mRNA was expressed mostly in peripheral blood cells, followed by slight expression in the spleen and thymus, whereas DOCK180 was expressed in all tissues tested except in peripheral blood cells [16].
  • ELMO proteins are also known to regulate actin cytoskeleton reorganization through activation of the small GTPbinding protein Rac via the ELMO-Dock180 complex [17].

Associations of DOCK1 with chemical compounds

  • These results suggest that DOCK180 is a new effector molecule which transduces signals from tyrosine kinases through the CRK adaptor protein [13].
  • Thus DOCK180 contained a phosphoinositide-binding domain, as did the other guanine nucleotide exchange factors with a Dbl homology domain, and was translocated to the plasma membrane on the activation of PI-3K [8].
  • Laminin-10/11 and fibronectin differentially regulate integrin-dependent Rho and Rac activation via p130(Cas)-CrkII-DOCK180 pathway [10].
  • Moreover, our data link another PS-dependent signal to the CrkII/Dock180/Rac1 module [18].
  • Identification of a DOCK180-related Guanine Nucleotide Exchange Factor That Is Capable of Mediating a Positive Feedback Activation of Cdc42 [19].

Regulatory relationships of DOCK1

  • We also found that ELMO1 regulated multiple Dock180 superfamily members to promote migration [15].
  • In contrast, membrane ruffling, but not cell contraction, requires Rac GTPase activity and the formation of a CAS/Crk complex that functions in the context of the Rac activating protein DOCK180 [20].
  • The ubiquitylation of Dock180 was enhanced by epidermal growth factor (EGF), Crk and adhesion-dependent signals [21].
  • Here, the author reports on the characterization of M-DOCK protein, which is closely related to DOCK180 but expressed only in the hematopoietic cells [22].
  • Lysyl oxidase regulates actin filament formation through the p130(Cas)/Crk/DOCK180 signaling complex [23].

Other interactions of DOCK1

  • DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane [13].
  • We have identified in a yeast two-hybrid screen DOCK180, a signaling protein implicated in the regulation of membrane ruffling and migration, as a binding protein for Nck-2 [12].
  • Here we show that RhoG interacts directly with Elmo in a GTP-dependent manner and forms a ternary complex with Dock180 to induce activation of Rac1 [24].
  • Both cDNAs encoded novel proteins: C3G, a guanine nucleotide exchange protein for Rap1, and DOCK180, an SH3-containing protein of unknown function [25].
  • Following the initial landmark finding that Grb2 adapter links the receptors to the Ras pathway leading to DNA synthesis, recent studies have revealed that the biological function of the SH2/SH3 adapter Nck/Dock is to link cell surface receptors to the actin cytoskeleton [26].

Analytical, diagnostic and therapeutic context of DOCK1


  1. Drosophila Ack targets its substrate, the sorting nexin DSH3PX1, to a protein complex involved in axonal guidance. Worby, C.A., Simonson-Leff, N., Clemens, J.C., Huddler, D., Muda, M., Dixon, J.E. J. Biol. Chem. (2002) [Pubmed]
  2. Bill Dock and the location of pulmonary tuberculosis: how bed rest might have helped consumption. Murray, J.F. Am. J. Respir. Crit. Care Med. (2003) [Pubmed]
  3. Turn-of-the-century nursing perspectives on venereal disease. Temkin, E. Image--the journal of nursing scholarship. (1994) [Pubmed]
  4. CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Gumienny, T.L., Brugnera, E., Tosello-Trampont, A.C., Kinchen, J.M., Haney, L.B., Nishiwaki, K., Walk, S.F., Nemergut, M.E., Macara, I.G., Francis, R., Schedl, T., Qin, Y., Van Aelst, L., Hengartner, M.O., Ravichandran, K.S. Cell (2001) [Pubmed]
  5. C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180. Wu, Y.C., Horvitz, H.R. Nature (1998) [Pubmed]
  6. Activation of Rac1 by a Crk SH3-binding protein, DOCK180. Kiyokawa, E., Hashimoto, Y., Kobayashi, S., Sugimura, H., Kurata, T., Matsuda, M. Genes Dev. (1998) [Pubmed]
  7. The Rac Activator DOCK7 Regulates Neuronal Polarity through Local Phosphorylation of Stathmin/Op18. Watabe-Uchida, M., John, K.A., Janas, J.A., Newey, S.E., Van Aelst, L. Neuron (2006) [Pubmed]
  8. Membrane recruitment of DOCK180 by binding to PtdIns(3,4,5)P3. Kobayashi, S., Shirai, T., Kiyokawa, E., Mochizuki, N., Matsuda, M., Fukui, Y. Biochem. J. (2001) [Pubmed]
  9. PH domain of ELMO functions in trans to regulate Rac activation via Dock180. Lu, M., Kinchen, J.M., Rossman, K.L., Grimsley, C., deBakker, C., Brugnera, E., Tosello-Trampont, A.C., Haney, L.B., Klingele, D., Sondek, J., Hengartner, M.O., Ravichandran, K.S. Nat. Struct. Mol. Biol. (2004) [Pubmed]
  10. Laminin-10/11 and fibronectin differentially regulate integrin-dependent Rho and Rac activation via p130(Cas)-CrkII-DOCK180 pathway. Gu, J., Sumida, Y., Sanzen, N., Sekiguchi, K. J. Biol. Chem. (2001) [Pubmed]
  11. Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity. Côté, J.F., Vuori, K. J. Cell. Sci. (2002) [Pubmed]
  12. Identification and kinetic analysis of the interaction between Nck-2 and DOCK180. Tu, Y., Kucik, D.F., Wu, C. FEBS Lett. (2001) [Pubmed]
  13. DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane. Hasegawa, H., Kiyokawa, E., Tanaka, S., Nagashima, K., Gotoh, N., Shibuya, M., Kurata, T., Matsuda, M. Mol. Cell. Biol. (1996) [Pubmed]
  14. alphavbeta5 integrin recruits the CrkII-Dock180-rac1 complex for phagocytosis of apoptotic cells. Albert, M.L., Kim, J.I., Birge, R.B. Nat. Cell Biol. (2000) [Pubmed]
  15. Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration. Grimsley, C.M., Kinchen, J.M., Tosello-Trampont, A.C., Brugnera, E., Haney, L.B., Lu, M., Chen, Q., Klingele, D., Hengartner, M.O., Ravichandran, K.S. J. Biol. Chem. (2004) [Pubmed]
  16. Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins. Nishihara, H., Kobayashi, S., Hashimoto, Y., Ohba, F., Mochizuki, N., Kurata, T., Nagashima, K., Matsuda, M. Biochim. Biophys. Acta (1999) [Pubmed]
  17. Characterization of a novel interaction between ELMO1 and ERM proteins. Grimsley, C.M., Lu, M., Haney, L.B., Kinchen, J.M., Ravichandran, K.S. J. Biol. Chem. (2006) [Pubmed]
  18. A role for Mer tyrosine kinase in alphavbeta5 integrin-mediated phagocytosis of apoptotic cells. Wu, Y., Singh, S., Georgescu, M.M., Birge, R.B. J. Cell. Sci. (2005) [Pubmed]
  19. Identification of a DOCK180-related Guanine Nucleotide Exchange Factor That Is Capable of Mediating a Positive Feedback Activation of Cdc42. Lin, Q., Yang, W., Baird, D., Feng, Q., Cerione, R.A. J. Biol. Chem. (2006) [Pubmed]
  20. Regulation of cell contraction and membrane ruffling by distinct signals in migratory cells. Cheresh, D.A., Leng, J., Klemke, R.L. J. Cell Biol. (1999) [Pubmed]
  21. Elmo1 inhibits ubiquitylation of Dock180. Makino, Y., Tsuda, M., Ichihara, S., Watanabe, T., Sakai, M., Sawa, H., Nagashima, K., Hatakeyama, S., Tanaka, S. J. Cell. Sci. (2006) [Pubmed]
  22. Analysis of hematopoietic cell specific protein, M-DOCK. Nishihara, H. Hokkaido Igaku Zasshi (1999) [Pubmed]
  23. Lysyl oxidase regulates actin filament formation through the p130(Cas)/Crk/DOCK180 signaling complex. Payne, S.L., Hendrix, M.J., Kirschmann, D.A. J. Cell. Biochem. (2006) [Pubmed]
  24. RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. Katoh, H., Negishi, M. Nature (2003) [Pubmed]
  25. Emerging components of the Crk oncogene product: the first identified adaptor protein. Matsuda, M., Kurata, T. Cell. Signal. (1996) [Pubmed]
  26. Nck/Dock: an adapter between cell surface receptors and the actin cytoskeleton. Li, W., Fan, J., Woodley, D.T. Oncogene (2001) [Pubmed]
  27. Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins. Matsuda, M., Ota, S., Tanimura, R., Nakamura, H., Matuoka, K., Takenawa, T., Nagashima, K., Kurata, T. J. Biol. Chem. (1996) [Pubmed]
  28. Chromosomal mapping of the gene encoding DOCK180, a major Crk-binding protein, to 10q26.13-q26.3 by fluorescence in situ hybridization. Takai, S., Hasegawa, H., Kiyokawa, E., Yamada, K., Kurata, T., Matsuda, M. Genomics (1996) [Pubmed]
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