title: Immune regulatory functions of DOCK family proteins in health and disease.
abstract: DOCK proteins constitute a family of evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho family of GTPases. Although DOCK family proteins do not contain the Dbl homology domain typically found in GEFs, they mediate the GTP-GDP exchange reaction through DHR-2 domain. Accumulating evidence indicates that the DOCK proteins act as major GEFs in varied biological settings. For example, DOCK2, which is predominantly expressed in hematopoietic cells, regulates migration and activation of leukocytes through Rac activation. On the other hand, it was recently reported that mutations of DOCK8, another member of the DOCK family proteins, cause a combined immunodeficiency syndrome in humans. This article reviews the structure, functions and signaling of DOCK2 and DOCK8, especially focusing on their roles in immune responses.
authors.affiliation: Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nishikimi
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Kukimoto-Niino
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fukui
mesh_terms: D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D020690:GTPase-Activating Proteins; D005786:Gene Expression Regulation / Q000276:immunology*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology; D008958:Models, Molecular; D009154:Mutation; D017434:Protein Structure, Tertiary; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: C402110:DOCK2 protein, human; C516591:DOCK8 protein, human; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D007370:Interferon Type I
keywords: Activation; Guanine nucleotide exchange factors; Leukocytes; Migration; Small GTPases