Dock180

Dock180 is a protein that plays a significant role in the regulation of cell migration and cytoskeletal reorganization. It is part of the DOCK (Dedicator of Cytokinesis) family, which is known for its involvement in intracellular signaling pathways. Dock180 functions as a guanine nucleotide exchange factor (GEF) for the Rho GTPase family member, Rac1, which is crucial for actin cytoskeleton rearrangements and, consequently, affects cell shape and movement.

Function

Dock180, through its interaction with Rac1, facilitates the exchange of GDP for GTP on Rac1, activating it. Active Rac1 then initiates a cascade of events leading to actin polymerization and the formation of structures such as lamellipodia and filopodia, which are essential for cell migration. This process is vital in various physiological and pathological contexts, including wound healing, immune response, and cancer metastasis.

Structure

The Dock180 protein contains several domains, including the SH3 domain, which is involved in protein-protein interactions, and the DOCK Homology Region 2 (DHR-2) domain, which is responsible for its GEF activity towards Rac1. The interaction between Dock180 and its partner protein, ELMO (Engulfment and Cell Motility protein), enhances its GEF activity and is necessary for the full activation of Rac1.

Clinical Significance

Alterations in the expression or function of Dock180 have been implicated in various diseases. In cancer, for example, overexpression of Dock180 has been observed in certain types of tumors and is associated with increased tumor cell migration and invasion, contributing to cancer progression and metastasis. Additionally, Dock180's role in immune cell migration makes it a potential target for therapeutic intervention in autoimmune diseases and inflammation.

Research

Research on Dock180 has provided insights into the molecular mechanisms of cell migration and has identified potential therapeutic targets for diseases characterized by abnormal cell migration. Further studies are necessary to fully understand the regulatory mechanisms controlling Dock180 activity and its interactions with other proteins in the cell.

See Also

• Rho GTPase
• Cell migration
• Cytoskeleton
• Cancer metastasis