A novel and evolutionarily conserved PtdIns(3,4,5)P<subscript>3</subscript>-binding domain is necessary for DOCK180 signalling.
In: Nature Cell Biology, Jg. 7 (2005-08-01), Heft 8, S. 797-807
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Zugriff:
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 A form of DOCK180 in which the DHR-1 domain has been replaced by a canonical PtdIns(3,4,5)P3-binding pleckstrin homology domain is fully functional at inducing cell elongation and migration, suggesting that the main function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. [ABSTRACT FROM AUTHOR]
Titel: |
A novel and evolutionarily conserved PtdIns(3,4,5)P<subscript>3</subscript>-binding domain is necessary for DOCK180 signalling.
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Autor/in / Beteiligte Person: | Côté, Jean-François ; Motoyama, Andrea B. ; Bush, Jason A. ; Vuori, Kristiina |
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Zeitschrift: | Nature Cell Biology, Jg. 7 (2005-08-01), Heft 8, S. 797-807 |
Veröffentlichung: | 2005 |
Medientyp: | academicJournal |
ISSN: | 1465-7392 (print) |
DOI: | 10.1038/ncb1280 |
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