Dock2

Summary

Gene Symbol: Dock2
Description: dedicator of cyto-kinesis 2
Alias: AI662014, AW122239, CED-5, Hch, MBC, dedicator of cytokinesis protein 2
Species: mouse
Products:     Dock2

Top Publications

  1. Reif K, Cyster J. The CDM protein DOCK2 in lymphocyte migration. Trends Cell Biol. 2002;12:368-73 pubmed
    ..This possibility has recently gained support from studies of mice deficient in DOCK2, a member of the Caenorhabditis elegans Ced-5, mammalian DOCK180 and Drosophila melanogaster myoblast city (CDM) ..
  2. Purtha W, Swiecki M, Colonna M, Diamond M, Bhattacharya D. Spontaneous mutation of the Dock2 gene in Irf5-/- mice complicates interpretation of type I interferon production and antibody responses. Proc Natl Acad Sci U S A. 2012;109:E898-904 pubmed publisher
    ..spontaneous genomic duplication and frameshift mutation in the guanine exchange factor dedicator of cytokinesis 2 (Dock2) that has arisen in at least a subset of circulating Irf5(-/-) mice and inadvertently been bred to homozygosity...
  3. Nishikimi A, Fukuhara H, Su W, Hongu T, Takasuga S, Mihara H, et al. Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. Science. 2009;324:384-7 pubmed publisher
    ..In neutrophils, Rac activation is primarily mediated by DOCK2, an atypical guanine nucleotide exchange factor...
  4. Jiang H, Pan F, Erickson L, Jang M, Sanui T, Kunisaki Y, et al. Deletion of DOCK2, a regulator of the actin cytoskeleton in lymphocytes, suppresses cardiac allograft rejection. J Exp Med. 2005;202:1121-30 pubmed
    ..b>DOCK2 plays a critical role in lymphocyte homing and immunological synapse formation by regulating the actin ..
  5. Hedlund M, Tangvoranuntakul P, Takematsu H, Long J, Housley G, Kozutsumi Y, et al. N-glycolylneuraminic acid deficiency in mice: implications for human biology and evolution. Mol Cell Biol. 2007;27:4340-6 pubmed
    ..Adult animals also showed delayed skin wound healing. Loss of Neu5Gc in hominid ancestors approximately 2 to 3 million years ago likely had immediate and long-term consequences for human biology. ..
  6. Gotoh K, Tanaka Y, Nishikimi A, Nakamura R, Yamada H, Maeda N, 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 pubmed publisher
    ..However, the signaling pathway mediating IKK-alpha activation is poorly defined. We show that DOCK2, an atypical Rac activator, is essential for TLR7- and TLR9-mediated IFN-alpha induction in pDCs...
  7. Gotoh K, Tanaka Y, Nishikimi A, Inayoshi A, Enjoji M, Takayanagi R, et al. Differential requirement for DOCK2 in migration of plasmacytoid dendritic cells versus myeloid dendritic cells. Blood. 2008;111:2973-6 pubmed publisher
    ..Here we show that DOCK2, a hematopoietic cell-specific CDM family protein, is indispensable for migration of plasmacytoid DCs (pDCs), but ..
  8. Sanui T, Inayoshi A, Noda M, Iwata E, Oike M, Sasazuki T, et al. DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-theta and LFA-1, in T cells. Immunity. 2003;19:119-29 pubmed
    b>DOCK2 is a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City which are known to regulate actin cytoskeleton...
  9. Nombela Arrieta C, Mempel T, Soriano S, Mazo I, Wymann M, Hirsch E, et al. A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate-mediated egress. J Exp Med. 2007;204:497-510 pubmed
    ..used MP-IVM of murine PLNs to examine interstitial motility of lymphocytes lacking the Rac guanine exchange factor DOCK2 and phosphoinositide-3-kinase (PI3K)gamma, signaling molecules that act downstream of G protein-coupled receptors, ..

More Information

Publications44

  1. Nombela Arrieta C, Lacalle R, Montoya M, Kunisaki Y, Megias D, Marqués M, et al. Differential requirements for DOCK2 and phosphoinositide-3-kinase gamma during T and B lymphocyte homing. Immunity. 2004;21:429-41 pubmed
    ..Here, we analyze the roles of DOCK2, a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City, and ..
  2. Kunisaki Y, Nishikimi A, Tanaka Y, Takii R, Noda M, Inayoshi A, et al. DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. J Cell Biol. 2006;174:647-52 pubmed
    ..We show that DOCK2, which is a mammalian homologue of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City, ..
  3. Shulman Z, Pasvolsky R, Woolf E, Grabovsky V, Feigelson S, Erez N, et al. DOCK2 regulates chemokine-triggered lateral lymphocyte motility but not transendothelial migration. Blood. 2006;108:2150-8 pubmed
    ..In lymphocytes, chemokine-mediated Rac activation depends on the CDM adaptor DOCK2. The present studies addressed the role of DOCK2 in chemokine-triggered lymphocyte adhesion and motility...
  4. Fukui Y, Hashimoto O, Sanui T, Oono T, Koga H, Abe M, et al. Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration. Nature. 2001;412:826-31 pubmed
    ..Here we show that DOCK2, a haematopoietic cell-specific CDM family protein, is indispensable for lymphocyte chemotaxis...
  5. Guo X, Li F, Xu Z, Yin A, Yin H, Li C, et al. DOCK2 deficiency mitigates HFD-induced obesity by reducing adipose tissue inflammation and increasing energy expenditure. J Lipid Res. 2017;58:1777-1784 pubmed publisher
    ..Dedicator of cytokinesis 2 (DOCK2) is involved in several inflammatory diseases, but its role in obesity remains unknown...
  6. Sakai Y, Tanaka Y, Yanagihara T, Watanabe M, Duan X, Terasawa M, et al. The Rac activator DOCK2 regulates natural killer cell-mediated cytotoxicity in mice through the lytic synapse formation. Blood. 2013;122:386-93 pubmed publisher
    ..Here, we show that DOCK2, an atypical guanine nucleotide exchange factor for Rac, plays a key role in NK cell-mediated cytotoxicity...
  7. Lei Y, Liu C, Saito F, Fukui Y, Takahama Y. Role of DOCK2 and DOCK180 in fetal thymus colonization. Eur J Immunol. 2009;39:2695-702 pubmed publisher
    ..Here we show that T-lymphoid progenitor cells in fetal mice express two closely related CDM family molecules, DOCK2 and DOCK180...
  8. Sai J, Raman D, Liu Y, Wikswo J, Richmond A. Parallel phosphatidylinositol 3-kinase (PI3K)-dependent and Src-dependent pathways lead to CXCL8-mediated Rac2 activation and chemotaxis. J Biol Chem. 2008;283:26538-47 pubmed publisher
    ..We hypothesized that Src-regulated ELMO-Dock2-Rac2 activation mediates chemotaxis in the absence of PI3K activity...
  9. Damoulakis G, Gambardella L, Rossman K, Lawson C, Anderson K, Fukui Y, et al. P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils. J Cell Sci. 2014;127:2589-600 pubmed publisher
    ..Loss of RhoG also impaired GPCR-driven recruitment of the Rac GEF DOCK2, and F-actin, to the leading edge of migrating neutrophils...
  10. Wu M, Hamaker M, Li L, Small D, Duffield A. DOCK2 interacts with FLT3 and modulates the survival of FLT3-expressing leukemia cells. Leukemia. 2017;31:688-696 pubmed publisher
    ..The screen identified dedicator of cytokinesis 2 (DOCK2), which is a guanine nucleotide exchange factor for Rho GTPases, and its expression is limited to hematolymphoid ..
  11. Mahajan V, Demissie E, Mattoo H, Viswanadham V, Varki A, Morris R, et al. Striking Immune Phenotypes in Gene-Targeted Mice Are Driven by a Copy-Number Variant Originating from a Commercially Available C57BL/6 Strain. Cell Rep. 2016;15:1901-9 pubmed publisher
    We describe a homozygous copy-number variant that disrupts the function of Dock2 in a commercially available C57BL/6 mouse strain that is widely used for backcrossing...
  12. Cariappa A, Takematsu H, Liu H, Diaz S, Haider K, Boboila C, et al. B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase. J Exp Med. 2009;206:125-38 pubmed publisher
    ..These results describe a novel catalytic regulator of B cell signaling and underscore the crucial role of inhibitory signaling in the maintenance of immunological tolerance in the B lineage. ..
  13. Gollmer K, Asperti Boursin F, Tanaka Y, Okkenhaug K, Vanhaesebroeck B, Peterson J, et al. CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway. Blood. 2009;114:580-8 pubmed publisher
    ..Conversely, deficiency in the Rac guanine exchange factor DOCK2 significantly impaired CCL21-mediated costimulation in TCR-tg CD4(+) T cells, concomitant with impaired Rac- but ..
  14. Kikuchi T, Kubonishi S, Shibakura M, Namba N, Matsui T, Fukui Y, et al. Dock2 participates in bone marrow lympho-hematopoiesis. Biochem Biophys Res Commun. 2008;367:90-6 pubmed
    b>Dock2 has been shown to be indispensable for chemotaxis of mature lymphocytes as a critical Rac activator. However, the functional expression of Dock2 in immature hematopoietic cells is unclear...
  15. Tanaka Y, Hamano S, Gotoh K, Murata Y, Kunisaki Y, Nishikimi A, et al. T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-alpha subunit controlled by the Rac activator Dock2. Nat Immunol. 2007;8:1067-75 pubmed
    ..Here we find that mice lacking Dock2, a Rac activator in lymphocytes, developed allergic disease through a mechanism dependent on CD4+ T cells and the ..
  16. Lazear H, Lancaster A, Wilkins C, Suthar M, Huang A, Vick S, et al. IRF-3, IRF-5, and IRF-7 coordinately regulate the type I IFN response in myeloid dendritic cells downstream of MAVS signaling. PLoS Pathog. 2013;9:e1003118 pubmed publisher
    ..Our results establish IRF-3, -5, and -7 as the key transcription factors responsible for mediating the type I IFN and ISG response in mDC during WNV infection and suggest a novel signaling link between MAVS and IRF-5. ..
  17. Kumar V, Scandella E, Danuser R, Onder L, Nitschké M, Fukui Y, et al. Global lymphoid tissue remodeling during a viral infection is orchestrated by a B cell-lymphotoxin-dependent pathway. Blood. 2010;115:4725-33 pubmed publisher
  18. Ogawa K, Tanaka Y, Uruno T, Duan X, Harada Y, Sanematsu F, et al. DOCK5 functions as a key signaling adaptor that links Fc?RI signals to microtubule dynamics during mast cell degranulation. J Exp Med. 2014;211:1407-19 pubmed publisher
    ..Our results thus identify DOCK5 as a key signaling adaptor that orchestrates remodeling of the microtubule network essential for mast cell degranulation. ..
  19. Guo X, Shi N, Cui X, Wang J, Fukui Y, Chen S. Dedicator of cytokinesis 2, a novel regulator for smooth muscle phenotypic modulation and vascular remodeling. Circ Res. 2015;116:e71-80 pubmed publisher
    ..The objective of this study is to determine the role of dedicator of cytokinesis 2 (DOCK2) in SMC phenotypic modulation and vascular remodeling...
  20. Andrews T, Whittle B, Field M, Balakishnan B, Zhang Y, Shao Y, et al. Massively parallel sequencing of the mouse exome to accurately identify rare, induced mutations: an immediate source for thousands of new mouse models. Open Biol. 2012;2:120061 pubmed publisher
    ..This approach transforms genetic screens in mice, establishes a general strategy for analysing rare DNA variants and opens up a large new source for experimental models of human disease. ..
  21. Rowton M, Ramos P, Anderson D, Rhee J, Cunliffe H, Rawls A. Regulation of mesenchymal-to-epithelial transition by PARAXIS during somitogenesis. Dev Dyn. 2013;242:1332-44 pubmed publisher
    ..These data demonstrate that PARAXIS initiates and stabilizes somite epithelialization by integrating signals from multiple pathways to control the reorganization of the ECM, cytoskeleton, and adhesion junctions during MET. ..
  22. Yasuda K, Nündel K, Watkins A, Dhawan T, Bonegio R, Ubellacker J, et al. Phenotype and function of B cells and dendritic cells from interferon regulatory factor 5-deficient mice with and without a mutation in DOCK2. Int Immunol. 2013;25:295-306 pubmed publisher
    ..A recent report identifies a mutation in dedicator of cytokinesis 2 (DOCK2) as being responsible for the abnormal B-cell development phenotype observed in the IRF5 (-/-) line...
  23. Wen Y, Elliott M, Huang Y, Miller T, Corbin D, Hussain L, 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 pubmed publisher
    ..Here, we provide data to support a critical role for dedicator of cytokinesis 2 (DOCK2) in multiple aspects of FCs function...
  24. WEISS M, Byrne A, Blazek K, Saliba D, Pease J, Perocheau D, et al. IRF5 controls both acute and chronic inflammation. Proc Natl Acad Sci U S A. 2015;112:11001-6 pubmed publisher
    ..These studies extend prior ones suggesting that inhibiting IRF5 might be useful for chronic macrophage-induced inflammation and suggest that IRF5 blockade would ameliorate more acute forms of inflammation, including lung injury. ..
  25. Watanabe M, Terasawa M, Miyano K, Yanagihara T, Uruno T, Sanematsu F, et al. DOCK2 and DOCK5 act additively in neutrophils to regulate chemotaxis, superoxide production, and extracellular trap formation. J Immunol. 2014;193:5660-7 pubmed publisher
    ..Neutrophil chemotaxis and ROS production require activation of Rac small GTPase. DOCK2, an atypical guanine nucleotide exchange factor (GEF), is one of the major regulators of Rac in neutrophils...
  26. Ackerknecht M, Gollmer K, Germann P, Ficht X, Abe J, Fukui Y, et al. Antigen Availability and DOCK2-Driven Motility Govern CD4+ T Cell Interactions with Dendritic Cells In Vivo. J Immunol. 2017;199:520-530 pubmed publisher
    Parenchymal migration of naive CD4+ T cells in lymph nodes (LNs) is mediated by the Rac activator DOCK2 and PI3K? and is widely assumed to facilitate efficient screening of dendritic cells (DCs) presenting peptide-MHCs (pMHCs)...
  27. Cimino P, Sokal I, Leverenz J, Fukui Y, Montine T. 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 pubmed publisher
    ..In this study, we link dedicator of cytokinesis 2 (DOCK2) to the prostaglandin pathway in the brain...
  28. Kunisaki Y, Tanaka Y, Sanui T, Inayoshi A, Noda M, Nakayama T, et al. DOCK2 is required in T cell precursors for development of Valpha14 NK T cells. J Immunol. 2006;176:4640-5 pubmed
    ..b>DOCK2, a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster myoblast city, is critical for ..
  29. Cimino P, Yang Y, Li X, Hemingway J, Cherne M, Khademi S, et al. Ablation of the microglial protein DOCK2 reduces amyloid burden in a mouse model of Alzheimer's disease. Exp Mol Pathol. 2013;94:366-71 pubmed publisher
    ..Dedicator of cytokinesis 2 (DOCK2) is a guanyl nucleotide exchange factor expressed exclusively in microglia in the brain and is regulated by PGE2 ..
  30. Stevenson C, de la Rosa G, Anderson C, Murphy P, Capece T, Kim M, et al. Essential role of Elmo1 in Dock2-dependent lymphocyte migration. J Immunol. 2014;192:6062-70 pubmed publisher
    ..In T lymphocytes, Dock2 is essential for CCR7- and CXCR4-dependent Rac activation and chemotaxis, but the role of Elmo proteins in ..
  31. Terasawa M, Uruno T, Mori S, Kukimoto Niino M, Nishikimi A, Sanematsu F, et al. Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration. PLoS ONE. 2012;7:e46277 pubmed publisher
    The migratory properties of lymphocytes depend on DOCK2, an atypical Rac activator predominantly expressed in hematopoietic cells...
  32. Arnold C, Pirie E, Dosenovic P, McInerney G, Xia Y, Wang N, et al. A forward genetic screen reveals roles for Nfkbid, Zeb1, and Ruvbl2 in humoral immunity. Proc Natl Acad Sci U S A. 2012;109:12286-93 pubmed publisher
    ..All of the mutations identified to date directly affect lymphocyte development or function; none have an exclusive effect on cells of the innate immune system. ..
  33. Fukui Y. [A critical role of the CDM family molecule DOCK2 in lymphocyte migration]. Tanpakushitsu Kakusan Koso. 2002;47:2194-9 pubmed
  34. Ippagunta S, Malireddi R, Shaw P, Neale G, Vande Walle L, Green D, et al. The inflammasome adaptor ASC regulates the function of adaptive immune cells by controlling Dock2-mediated Rac activation and actin polymerization. Nat Immunol. 2011;12:1010-6 pubmed publisher
    ..that ASC, but not the cytoplasmic receptor NLRP3 or caspase-1, controlled the mRNA stability and expression of Dock2, a guanine nucleotide-exchange factor that mediates Rac-dependent signaling in cells of the immune response...
  35. Nakasaki T, Tanaka T, Okudaira S, Hirosawa M, Umemoto E, Otani K, et al. Involvement of the lysophosphatidic acid-generating enzyme autotaxin in lymphocyte-endothelial cell interactions. Am J Pathol. 2008;173:1566-76 pubmed publisher
    ..Tissue-specific inactivation of ATX will verify this hypothesis in future studies of its mechanism of action. ..