Biology:Dock11
 Generic protein structure example |
Dock11 (Dedicator of cytokinesis), also known as Zizimin2, is a large (~240 kDa) protein involved in intracellular signalling networks.[1][2] 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.
Discovery
Dock11 was identified as a protein which is highly expressed in Germinal center B lymphocytes.[3] 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.[4]
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.[3] It contains a DHR2 domain which mediates GEF activity and a DHR1 domain which may interact with membrane phospholipids. It also contains an N-terminal PH domain which may be involved in its recruitment to the plasma membrane. Dock11 binds and activates nucleotide-free Cdc42 via its DHR2 domain[3] and has also been reported to mediate positive feedback on active, GTP-bound Cdc42,[5] 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.[6] Gene expression studies have suggested that Dock11 may have a role in the development of pituitary and testicular tumours.[4][7]
References
- ↑ "Entrez Gene: DOCK11 dedicator of cytokinesis 11". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=139818.
- ↑ "Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity". Journal of Cell Science 115 (Pt 24): 4901–13. December 2002. doi:10.1242/jcs.00219. PMID 12432077.
- ↑ 3.0 3.1 3.2 "Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes". FEBS Letters 579 (5): 1039–46. February 2005. doi:10.1016/j.febslet.2005.01.006. PMID 15710388.
- ↑ 4.0 4.1 "Differential gene expression of p27Kip1 and Rb knockout pituitary tumors associated with altered growth and angiogenesis". Cell Cycle 6 (6): 750–7. March 2007. doi:10.4161/cc.6.6.3986. PMID 17361101.
- ↑ "Identification of a DOCK180-related guanine nucleotide exchange factor that is capable of mediating a positive feedback activation of Cdc42". The Journal of Biological Chemistry 281 (46): 35253–62. November 2006. doi:10.1074/jbc.M606248200. PMID 16968698.
- ↑ "Cellular signaling for activation of Rho GTPase Cdc42". Cellular Signalling 20 (11): 1927–34. November 2008. doi:10.1016/j.cellsig.2008.05.002. PMID 18558478.
- ↑ "Improved gene expression signature of testicular carcinoma in situ". International Journal of Andrology 30 (4): 292–302; discussion 303. August 2007. doi:10.1111/j.1365-2605.2007.00758.x. PMID 17488342.
Further reading
- "GEF what? Dock180 and related proteins help Rac to polarize cells in new ways". Trends in Cell Biology 17 (8): 383–93. August 2007. doi:10.1016/j.tcb.2007.05.001. PMID 17765544.
- "In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains". Methods in Enzymology 406: 41–57. 2006. doi:10.1016/S0076-6879(06)06004-6. ISBN 9780121828110. PMID 16472648.
- "CZH proteins: a new family of Rho-GEFs". Journal of Cell Science 118 (Pt 21): 4937–46. November 2005. doi:10.1242/jcs.02671. PMID 16254241.
- "Dock10, a novel CZH protein selectively induced by interleukin-4 in human B lymphocytes". Molecular Immunology 45 (12): 3411–8. July 2008. doi:10.1016/j.molimm.2008.04.003. PMID 18499258.
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