Dedicator of cytokinesis protein 6 explained

Dedicator of cytokinesis protein 6 (Dock6), also known as Zir1 is a large (~200 kDa) protein encoded in the human by the DOCK6 gene, involved in intracellular signalling networks.^[1] It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors which function as activators of small G-proteins.

Discovery

Dock6 was identified as one of a family of proteins which share high sequence similarity with Dock180, the archetypal member of the DOCK family.^[2] It has a similar domain arrangement to other DOCK proteins,^[3] with a DHR1 domain known in other proteins to bind phospholipids,^[4] and a DHR2 domain containing the GEF activity.^[5]

Function

There is currently very little information about the cellular role of this protein. However, Dock6 has been reported to exhibit dual GEF specificity towards the small G proteins Rac1 and Cdc42.^[6] It is the only DOCK family member reported to activate both of these G proteins. The same study also showed that transfection of the Dock6 DHR2 domain into N1E-115 neuroblastoma cells promoted Rac- and Cdc42-dependent neurite outgrowth, although the physiological significance of this has yet to be demonstrated.

Further reading

• Côté JF, Vuori K . GEF what? Dock180 and related proteins help Rac to polarize cells in new ways. Trends Cell Biol. . 17 . 8. 383–93. 2007 . 17765544 . 10.1016/j.tcb.2007.05.001 . 2887429.
• Kwofie MA, Skowronski J . Specific recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 guanine nucleotide exchange factors. J. Biol. Chem. . 283 . 6. 3088–96. 2008 . 18056264 . 10.1074/jbc.M705170200. free .
• Katoh H, Negishi M . RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. Nature . 424 . 6947. 461–64. 2003 . 12879077 . 10.1038/nature01817. 2003Natur.424..461K . 4411133.

Notes and References

1. Web site: Entrez gene: DOCK6 dedicator of cytokinesis 6.
2. Côté JF, Vuori K . Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity . J. Cell Sci. . 115 . Pt 24 . 4901–13 . December 2002 . 12432077 . 10.1242/jcs.00219. free .
3. Meller N, Merlot S, Guda C . CZH proteins: a new family of Rho-GEFs . J. Cell Sci. . 118 . Pt 21 . 4937–46. November 2005 . 16254241 . 10.1242/jcs.02671. free .
4. Côté JF, Motoyama AB, Bush JA, Vuori K . A novel and evolutionarily conserved PtdIns(3,4,5)P3-binding domain is necessary for DOCK180 signaling. Nat. Cell Biol. . 7 . 8 . 797–807. August 2005 . 16025104 . 10.1038/ncb1280. 1352170 .
5. Book: Côté JF, Vuori K . In Vitro Guanine Nucleotide Exchange Activity of DHR-2/DOCKER/CZH2 Domains . 2006 . Regulators and Effectors of Small GTPases: Rho Family . Methods in Enzymology . 406 . 41–57 . 10.1016/S0076-6879(06)06004-6 . 978-0-12-182811-0 . 16472648.
6. Miyamoto Y, Yamauchi J, Sanbe A, Tanoue A . Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulates neurite outgrowth. Exp. Cell Res. . 313 . 4 . 791–804. February 2007 . 17196961 . 10.1016/j.yexcr.2006.11.017.