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EnglishDiacylglycerol 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 DGKα 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 DGKα coordinates the localization of Rac. We show that upon hepatocyte growth-factor stimulation, DGKα, by producing PA, provides a key signal to recruit atypical PKCζ/ι (aPKCζ/ι) in complex with RhoGDI and Rac at ruffling sites of colony-growing epithelial cells. Then, DGKα-dependent activation of aPKCζ/ι 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 DGKα 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.
| Titolo: | Diacylglycerol kinase α mediates HGF-induced Rac activation and membrane ruffling by regulating atypical PKC and RhoGDI |
| Autori Riconosciuti: | |
| Autori: | Federica Chianale; Elena Rainero; Cristina Cianflonea; Valentina Bettio;Andrea Pighini; Paolo Porporato; Nicoletta Filigheddu; Guido Serini; Fabiola Sinigaglia; Gianluca Baldanzi; Andrea Graziani |
| Data di pubblicazione: | 2010 |
| Abstract: | 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 DGKα 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 DGKα coordinates the localization of Rac. We show that upon hepatocyte growth-factor stimulation, DGKα, by producing PA, provides a key signal to recruit atypical PKCζ/ι (aPKCζ/ι) in complex with RhoGDI and Rac at ruffling sites of colony-growing epithelial cells. Then, DGKα-dependent activation of aPKCζ/ι 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 DGKα 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. |
| Volume: | 107(9) |
| Pagina iniziale: | 4182 |
| Pagina finale: | 4187 |
| Digital Object Identifier (DOI): | 10.1073/pnas.0908326107 |
| URL: | http://www.pnas.org/content/107/9/4182.abstract |
| Parole Chiave: | cell migration; growth factors; phosphatidic acid |
| Rivista: | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA |
| Appare nelle tipologie: | 03A-Articolo su Rivista |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| Chianale et al_PNAS_2010.pdf | POSTPRINT (VERSIONE FINALE DELL’AUTORE) | Accesso riservato | Utenti riconosciuti Richiedi una copia | |
| PNAS-2010-Chianale-4182-7.pdf | N/A | Utenti riconosciuti Richiedi una copia |
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