Skip to main content

DOCK2; Dedicator of Cytokinesis 2

  • Reference work entry
  • First Online:
  • 49 Accesses

Synonyms

FLJ46592; KIAA0209

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 via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   4,499.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   4,499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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(6):2973.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Lu M, Kinchen JM, Rossman KL, Grimsley C, de Bakker 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hiroshi Nishihara .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Nishihara, H. (2018). DOCK2; Dedicator of Cytokinesis 2. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_518

Download citation

Publish with us

Policies and ethics