Dock11 (Dedicator of cytokinesis), also known as Zizimin2, is a large (~240 kDa) protein involved in intracellularsignalling networks.[5][6] It is a member of the DOCK-D subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock11 activates the small G protein Cdc42.
Dock11 was identified as a protein which is highly expressed in Germinal centerB lymphocytes.[7] Subsequent RT-PCR analysis revealed expression of this protein in the spleen, thymus, bone marrow and in peripheral blood lymphocytes. Dock11 is expressed at lower levels in NIH-3T3 fibroblasts, C2C12 myoblasts and Neuro-2A neuroblastoma cells. Dock11 mRNA has also been detected in the pars intermedia.[8]
Structure and function[]
Dock11 exhibits the same domain arrangement as other members of the DOCK-D/Zizimin subfamily and shares the highest level of sequence identity with Dock9.[7] It contains a DHR2 domain which mediates GEF activity and a DHR1 domain which may interact with membranephospholipids. It also contains an N-terminalPH domain which may be involved in its recruitment to the plasma membrane. Dock11 binds and activates nucleotide-free Cdc42 via its DHR2 domain[7] and has also been reported to mediate positive feedback on active, GTP-bound Cdc42,[9] although this interaction required a small N-terminal region of Dock11 in addition to the DHR2 domain. Cdc42 in turn regulates signaling pathways that control diverse cellular functions including morphology, migration, endocytosis and cell cycle progression.[10] Gene expression studies have suggested that Dock11 may have a role in the development of pituitary and testicular tumours.[8][11]
Côté JF, Vuori K (2006). "In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains". Methods in Enzymology. 406: 41–57. doi:10.1016/S0076-6879(06)06004-6. PMID16472648.
Yelo E, Bernardo MV, Gimeno L, Alcaraz-García MJ, Majado MJ, Parrado A (July 2008). "Dock10, a novel CZH protein selectively induced by interleukin-4 in human B lymphocytes". Molecular Immunology. 45 (12): 3411–8. doi:10.1016/j.molimm.2008.04.003. PMID18499258.
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