We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A novel and evolutionarily conserved PtdIns(3,4,5)P<sub>3</sub>-binding domain is necessary for DOCK180 signalling.
- Authors
Côté, Jean-François; Motoyama, Andrea B.; Bush, Jason A.; Vuori, Kristiina
- Abstract
The evolutionarily conserved DOCK180 protein has an indispensable role in cell migration by functioning as an exchange factor for Rac GTPase via its DOCK homology region (DHR)-2 domain. We report here that the conserved DHR-1 domain also has an important signalling role. A form of DOCK180 that lacks DHR-1 fails to promote cell migration, although it is capable of inducing Rac GTP-loading. The DHR-1 domain interacts with PtdIns(3,4,5)P3 in vitro and in vivo, and mediates the DOCK180 signalling complex localization at sites of PtdIns(3,4,5)P3 accumulation in the cell's leading edge. A form of DOCK180 in which the DHR-1 domain has been replaced by a canonical PtdIns(3,4,5)P3-binding pleckstrin homology domain is fully functional at inducing cell elongation and migration, suggesting that the main function of DHR-1 is to bind PtdIns(3,4,5)P3. These results demonstrate that DOCK180, via its DHR-1 and DHR-2 domains, couples PtdIns(3,4,5)P3 signalling to Rac GTP-loading, which is essential for directional cell movement.
- Publication
Nature Cell Biology, 2005, Vol 7, Issue 8, p797
- ISSN
1465-7392
- Publication type
Academic Journal
- DOI
10.1038/ncb1280