期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：9
页码：4182-4187
DOI：10.1073/pnas.0908326107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Diacylglycerol kinases (DGKs) convert diacylglycerol (DAG) into phosphatidic acid (PA), acting as molecular switches between DAG- and PA-mediated signaling. We previously showed that Src-dependent activation and plasma membrane recruitment of DGK are required for growth-factor-induced cell migration and ruffling, through the control of Rac small-GTPase activation and plasma membrane localization. Herein we unveil a signaling pathway through which DGK coordinates the localization of Rac. We show that upon hepatocyte growth-factor stimulation, DGK, by producing PA, provides a key signal to recruit atypical PKC{zeta}/{iota} (aPKC{zeta}/{iota}) in complex with RhoGDI and Rac at ruffling sites of colony-growing epithelial cells. Then, DGK-dependent activation of aPKC{zeta}/{iota} mediates the release of Rac from the inhibitory complex with RhoGDI, allowing its activation and leading to formation of membrane ruffles, which constitute essential requirements for cell migration. These findings highlight DGK as the central element of a lipid signaling pathway linking tyrosine kinase growth-factor receptors to regulation of aPKCs and RhoGDI, and providing a positional signal regulating Rac association to the plasma membrane.
