Encyclopedia of Medical Immunology

Living Edition
| Editors: Ian MacKay, Noel R. Rose

Dedicator of Cytokinesis 2: DOCK2 Deficiency

  • R. P. NelsonJrEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9209-2_104-1



The Rho families GTPases regulate membrane polarization and cytoskeletal dynamics fundamental to cell migration. The protein families Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City (CDM), associated with the gene product of avian sarcoma virus CT10 (CRK), function to extend cell membranes (Nishihara et al. 1999). A mammalian homologue to the CDM family, dedicator of cytokinesis 2 (DOCK2) binds and activates Rac family small GTPase 1 (Rac1) and associates with engulfment and cell motility (ELMO1) through its Src-homology 3 (SH3) domain (Sanui et al. 2003). This signaling matrix regulates cytoskeletal reorganization through Ras-related C3 botulinum toxin substrate (Rac) that generates actin-rich lamelli-podial protrusions that drive movement. DOCK2 is expressed predominantly in peripheral blood cells, less in the spleen and thymus, and enables T- and B-lymphocytes to...

This is a preview of subscription content, log in to check access.


  1. Dobbs K, Dominguez Conde C, Zhang SY, et al. Inherited DOCK2 deficiency in patients with early-onset invasive infections. N Engl J Med. 2015;372:2409–22.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Fukui Y, Hashimoto O, Sanui T, et al. Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration. Nature. 2001;412:826–31.CrossRefPubMedGoogle Scholar
  3. Gotoh K, Tanaka Y, Nishikimi A, et al. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Kunisaki Y, Nishikimi A, Tanaka Y, et al. DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. J Cell Biol. 2006a;174:647–52.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Kunisaki Y, Tanaka Y, Sanui T, et al. DOCK2 is required in T cell precursors for development of Valpha14 NK T cells. J Immunol. 2006b;176:4640–5.CrossRefPubMedGoogle Scholar
  6. Nishihara H, Kobayashi S, Hashimoto Y, et al. Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins. Biochim Biophys Acta. 1999;1452:179–87.CrossRefPubMedGoogle Scholar
  7. Sanui T, Inayoshi A, Noda M, et al. DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1. Blood. 2003;102:2948–50.CrossRefPubMedGoogle Scholar
  8. Watanabe M, Terasawa M, Miyano K, et al. DOCK2 and DOCK5 act additively in neutrophils to regulate chemotaxis, superoxide production, and extracellular trap formation. J Immunol. 2014;193:5660–7.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Wen Y, Elliott MJ, Huang Y, et al. DOCK2 is critical for CD8(+) TCR(−) graft facilitating cells to enhance engraftment of hematopoietic stem and progenitor cells. Stem Cells. 2014;32:2732–43.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Professor of Medicine and PediatricsIndiana University School of Medicine Immunohematology and TransplantationIndianapolisUSA
  2. 2.Riley Hospital for Children at Indiana University HealthIndianapolisUSA

Section editors and affiliations

  • M Teresa de la Morena
    • 1
  • Robert P. Nelson
    • 2
  1. 1.University of Washington and Seattle Children's HospitalSeattleUSA
  2. 2.Hematology and OncologyIndiana UniversityIndianapolisUSA