Encyclopedia of Signaling Molecules

2012 Edition
| Editors: Sangdun Choi

DOCK2; Dedicator of Cytokinesis 2

Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-0461-4_518


Historical Background

DOCK2 was initially designated by Nishihara et al. in 1999 (Nishihara et al. 1999) as a hematopoietic cell-specific homologue of the CDM (ced-5 of Caenorhabditis elegans, DOCK180 of humans, and myoblast city of Drosophila melanogaster) family proteins. The name “DOCK” was originally designated as “Downstream of CRK” for DOCK180, an archetype of CDM family proteins in 1996 (Hasegawa et al. 1996).

Molecular Mechanism of DOCK2 as a Rac-Specific GEF (Guanine Nucleotide Exchange Factor)

In mammals, 11 DOCK180-related proteins have been identified, and the family members can be subcategorized into four groups denoted DOCK-A, -B, -C, and -D, and DOCK2 belongs to DOCK-A as well as DOCK180 (Fig.  1a) (Cote and Vuori 2007). The structural analysis revealed that DOCK2 consists of an SH3 domain in the N-terminus and DHR (DOCK homology region) -1/2 in the middle to C-terminus (Fig.  1b) (Cote and Vuori 2002). DHR-2 is highly conserved throughout...
This is a preview of subscription content, log in to check access.


  1. Cimino PJ, Sokal I, Leverenz J, Fukui Y, Montine TJ. DOCK2 is a microglial specific regulator of central nervous system innate immunity found in normal and Alzheimer’s disease brain. Am J Pathol. 2009;175:1622–30.PubMedCrossRefGoogle Scholar
  2. Cote JF, Vuori K. Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity. J Cell Sci. 2002;115:4901–13.PubMedCrossRefGoogle Scholar
  3. Cote JF, Vuori K. GEF what? Dock180 and related proteins help Rac to polarize cells in new ways. Trends Cell Biol. 2007;17:383–93.PubMedCrossRefGoogle Scholar
  4. Fukui Y, Hashimoto O, Sanui T, Oono T, Koga H, Abe M, Inayoshi A, Noda M, Oike M, Shirai T, Sasazuki T. Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration. Nature. 2001;412:826–31.PubMedCrossRefGoogle Scholar
  5. Garcia-Bernal D, Sotillo-Mallo E, Nombela-Arrieta C, Samaniego R, Fukui Y, Stein JV, Teixido J. DOCK2 is required for chemokine-promoted human T lymphocyte adhesion under shear stress mediated by the integrin alpha4beta1. J Immunol. 2006;177:5215–25.PubMedGoogle Scholar
  6. Gollmer K, Asperti-Boursin F, Tanaka Y, Okkenhaug K, Vanhaesebroeck B, Peterson JR, Fukui Y, Donnadieu E, Stein JV. CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway. Blood. 2009;114:580–8.PubMedCrossRefGoogle Scholar
  7. Gotoh K, Tanaka Y, Nishikimi A, Inayoshi A, Enjoji M, Takayanagi R, Sasazuki T, Fukui Y. Differential requirement for DOCK2 in migration of plasmacytoid dendritic cells versus myeloid dendritic cells. Blood. 2008;111:2973–6.PubMedCrossRefGoogle Scholar
  8. Gotoh K, Tanaka Y, Nishikimi A, Nakamura R, Yamada H, Maeda N, Ishikawa T, Hoshino K, Uruno T, Cao Q, Higashi S, Kawaguchi Y, Enjoji M, Takayanagi R, Kaisho T, Yoshikai Y, Fukui Y. Selective control of type I IFN induction by the Rac activator DOCK2 during TLR-mediated plasmacytoid dendritic cell activation. J Exp Med. 2010;207:721–30.PubMedCrossRefGoogle Scholar
  9. Hasegawa H, Kiyokawa E, Tanaka S, Nagashima K, Gotoh N, Shibuya M, Kurata T, Matsuda M. DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane. Mol Cell Biol. 1996;16:1770–6.PubMedGoogle Scholar
  10. Janardhan A, Swigut T, Hill B, Myers MP, Skowronski J. HIV-1 Nef binds the DOCK2-ELMO1 complex to activate rac and inhibit lymphocyte chemotaxis. PLoS Biol. 2004;2:E6.PubMedCrossRefGoogle Scholar
  11. Jiang H, Pan F, Erickson LM, Jang MS, Sanui T, Kunisaki Y, Sasazuki T, Kobayashi M, Fukui Y. Deletion of DOCK2, a regulator of the actin cytoskeleton in lymphocytes, suppresses cardiac allograft rejection. J Exp Med. 2005;202:1121–30.PubMedCrossRefGoogle Scholar
  12. Kunisaki Y, Nishikimi A, Tanaka Y, Takii R, Noda M, Inayoshi A, Watanabe K, Sanematsu F, Sasazuki T, Sasaki T, Fukui Y. DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. J Cell Biol. 2006a;174:647–52.PubMedCrossRefGoogle Scholar
  13. Kunisaki Y, Tanaka Y, Sanui T, Inayoshi A, Noda M, Nakayama T, Harada M, Taniguchi M, Sasazuki T, Fukui Y. DOCK2 is required in T cell precursors for development of Valpha14 NK T cells. J Immunol. 2006b;176:4640–5.PubMedGoogle Scholar
  14. Lu M, Kinchen JM, Rossman KL, Grimsley C, deBakker C, Brugnera E, Tosello-Trampont AC, Haney LB, Klingele D, Sondek J, Hengartner MO, Ravichandran KS. PH domain of ELMO functions in trans to regulate Rac activation via Dock180. Nat Struct Mol Biol. 2004;11:756–62.PubMedCrossRefGoogle Scholar
  15. Nishihara H, Kobayashi S, Hashimoto Y, Ohba F, Mochizuki N, Kurata T, Nagashima K, Matsuda M. Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins. Biochim Biophys Acta. 1999;1452:179–87.PubMedCrossRefGoogle Scholar
  16. Nishihara H, Maeda M, Oda A, Tsuda M, Sawa H, Nagashima K, Tanaka S. DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines. Blood. 2002a;100:3968–74.PubMedCrossRefGoogle Scholar
  17. Nishihara H, Maeda M, Tsuda M, Makino Y, Sawa H, Nagashima K, Tanaka S. DOCK2 mediates T cell receptor-induced activation of Rac2 and IL-2 transcription. Biochem Biophys Res Commun. 2002b;296:716–20.PubMedCrossRefGoogle Scholar
  18. Sanui T, Inayoshi A, Noda M, Iwata E, Oike M, Sasazuki T, Fukui Y. DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-theta and LFA-1, in T cells. Immunity. 2003a;19:119–29.PubMedCrossRefGoogle Scholar
  19. Sanui T, Inayoshi A, Noda M, Iwata E, Stein JV, Sasazuki T, Fukui Y. DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1. Blood. 2003b;102:2948–50.PubMedCrossRefGoogle Scholar
  20. Wang L, Nishihara H, Kimura T, Kato Y, Tanino M, Nishio M, Obara M, Endo T, Koike T, Tanaka S. DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma. Biochem Biophys Res Commun. 2010;395:111–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Graduate School of Medicine, Laboratory of Translational PathologyHokkaido UniversitySapporoJapan