Display Settings:


Send to:

Choose Destination
Nat Cell Biol. 2005 Aug;7(8):797-807. Epub 2005 Jul 17.

A novel and evolutionarily conserved PtdIns(3,4,5)P3-binding domain is necessary for DOCK180 signalling.

Author information

  • 1The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.


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)P(3) in vitro and in vivo, and mediates the DOCK180 signalling complex localization at sites of PtdIns(3,4,5)P(3) 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 A form of DOCK180 in which the DHR-1 domain has been replaced by a canonical PtdIns(3,4,5)P(3)-binding pleckstrin homology domain is fully functional at inducing cell elongation and migration, suggesting that the main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)P(3). These results demonstrate that DOCK180, via its DHR-1 and DHR-2 domains, couples PtdIns(3,4,5)P(3) signalling to Rac GTP-loading, which is essential for directional cell movement.

Comment in

[PubMed - indexed for MEDLINE]
Free PMC Article

Images from this publication.See all images (7)Free text

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig 6
Fig. 7
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk