Dock11

Dock11 (Dedicator of cytokinesis), also known as Zizimin2, is a large (~240 kDa) is_associated_with::protein involved in is_associated_with::intracellular signalling networks. It is a member of the DOCK-D subfamily of the DOCK family of is_associated_with::guanine nucleotide exchange factors (GEFs) which function as activators of small is_associated_with::G proteins. Dock11 activates the small G protein is_associated_with::Cdc42.

Discovery
Dock11 was identified as a protein which is highly expressed in is_associated_with::Germinal center is_associated_with::B lymphocytes. Subsequent is_associated_with::RT-PCR analysis revealed expression of this protein in the is_associated_with::spleen, is_associated_with::thymus, is_associated_with::bone marrow and in is_associated_with::peripheral blood lymphocytes. Dock11 is expressed at lower levels in NIH-3T3 fibroblasts, C2C12 is_associated_with::myoblasts and Neuro-2A is_associated_with::neuroblastoma cells. Dock11 is_associated_with::mRNA has also been detected in the is_associated_with::pars intermedia.

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 is_associated_with::Dock9. It contains a is_associated_with::DHR2 domain which mediates GEF activity and a is_associated_with::DHR1 domain which may interact with membrane is_associated_with::phospholipids. It also contains an is_associated_with::N-terminal is_associated_with::PH domain which may be involved in its recruitment to the is_associated_with::plasma membrane. Dock11 binds and activates is_associated_with::nucleotide-free Cdc42 via its DHR2 domain and has also been reported to mediate is_associated_with::positive feedback on active, GTP-bound Cdc42, 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, is_associated_with::endocytosis and is_associated_with::cell cycle progression. Gene expression studies have suggested that Dock11 may have a role in the development of is_associated_with::pituitary and testicular tumours.