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Reports
Inhibition of PI3K induces Rac Activation and Membrane Ruffling in Proto-Dbl Expressing Cells
Cristina Vanni, Vincenzo Visco, Alessia Parodi, Catherine Ottaviano, Marzia Ognibene, Andrea D Manazza, Saverio Francesco Retta, Luigi Varesio, Patrizia Mancini, Maria Rosaria Torrisi and Alessandra Eva
volume 5 | issue 22
15 november 2006Pages: 2657 - 2665
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Proto-Dbl protein, a guanine nucleotide exchange factor (GEF) for Rho GTPases, is tightly regulated by a combination of mechanisms that involve intra- and intermolecular interaction and N- and C-terminal domain-dependent turnover of the protein. Moreover, the interaction of the PH domain of proto-Dbl with phosphoinositides regulates its subcellular localization and biological activity. Here we show that inhibition of the phosphatidylinositol 3-kinase (PI3K) by molecular and pharmacological inhibitors causes a strong inhibition of proto-Dbl-induced cell proliferation and transformation. Conversely, inhibition of PI3K results in the translocation of proto-Dbl to the plasma membrane, Rac activation and increased membrane ruffles and cell motility. Furthermore, we investigated the signaling molecules involved in proto-Dbl-induced cell transformation and motility and observed that inhibition of PI3K in proto-Dbl expressing cells induces an increase in p38 activity and a decrease in ERK phosphorylation. Our results suggest that proto-Dbl activates distinct downstream effectors to induce morphological changes and cell transformation.
Authors
Cristina Vanni
Istituto G. Gaslini, Genova, Italy
Vincenzo Visco
University of Rome, Rome, Italy
Alessia Parodi
Istituto G. Gaslini, Genova, Italy
Catherine Ottaviano
Istituto G. Gaslini, Genova, Italy
Marzia Ognibene
Istituto G. Gaslini, Genova, Italy
Andrea D Manazza
Università di Torino, Torino, Italy
Saverio Francesco Retta
Università di Torino, Torino, Italy
Luigi Varesio
Istituto G. Gaslini; Genova, Italy
Patrizia Mancini
University of Rome, Rome, Italy
Maria Rosaria Torrisi
University of Rome, Rome, Italy
Alessandra Eva
Istituto G. Gaslini, Genova, Italy
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.