Dock11

Dock11 (Dedicator of cytokinesis), also known as Zizimin2, is a large (~240 kDa) protein involved in intracellular signalling networks.^[3][4] 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.^[5] 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.^[6]

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.^[5] 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^[5] and has also been reported to mediate positive feedback on active, GTP-bound Cdc42,^[7] 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.^[8] Gene expression studies have suggested that Dock11 may have a role in the development of pituitary and testicular tumours.^[6][9]

References

Further reading