Diacylglycerol kinase α mediates HGF-induced Rac activation and membrane ruffling by regulating atypical PKC and RhoGDI

• DOI: 10.1073/pnas.0908326107
• Publication Date: 2010-02-17T04:49:50Z
• Authors: Federica Chianale; Elena Rainero; Cristina Cianflone; Valentina Bettio; Andrea Pighini; Paolo E. Porporato; Nicoletta Filigheddu; Guido Serini; Fabiola Sinigaglia; Gianluca Baldanzi; Andrea Graziani
• Keywords: Membrane ruffling; Rac GTP-Binding Proteins; Cell Signaling

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 plasma membrane recruitment of DGKα are required for growth-factor-induced cell migration ruffling, through the control Rac small-GTPase localization. Herein we unveil a signaling pathway which coordinates localization Rac. show upon hepatocyte growth-factor stimulation, DGKα, by producing PA, provides key signal to recruit atypical PKCζ/ι (aPKCζ/ι) in complex with RhoGDI at ruffling sites colony-growing epithelial cells. Then, DGKα-dependent aPKCζ/ι mediates release from inhibitory RhoGDI, allowing its leading formation ruffles, constitute essential requirements migration. These findings highlight central element lipid linking tyrosine kinase receptors regulation aPKCs providing positional regulating association membrane.