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

被引：183

作者：

Côté, JF ^{[1
]}

Motoyama, AB ^{[1
]}

Bush, JA ^{[1
]}

Vuori, K ^{[1
]}

机构：

[1] Burnham Inst, La Jolla, CA 92037 USA

来源：

NATURE CELL BIOLOGY | 2005年 / 7卷 / 08期

关键词：

D O I：

10.1038/ncb1280

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 A form of DOCK180 in which the DHR-1 domain has been replaced by a canonical PtdIns(3,4,5)P-3-binding pleckstrin homology domain is fully functional at inducing cell elongation and migration, suggesting that the main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.

引用

页码：797 / U63

页数：15

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