Phosphoinositide 3-kinase C2β regulates cytoskeletal organization and cell migration via Rac-dependent mechanisms

Roy M. Katso, Olivier E. Pardo, Andrea Palamidessi, Clemens M. Franz, Marin Marinov, Angela De Laurentiis, Julian Downward, Giorgio Scita, Anne J. Ridley, Michael D. Waterfield, Alexandre Arcaro

Research output: Contribution to journalArticle

Abstract

Receptor-linked class I phosphoinositide 3-kinases (PI3Ks) induce assembly of signal transduction complexes through protein-protein and protein-lipid interactions that mediate cell proliferation, survival, and migration. Although class II PI3Ks have the potential to make the same phosphoinositides as class I PI3Ks, their precise cellular role is currently unclear. In this report, we demonstrate that class II phosphoinositide 3-kinase C2β (PI3KC2β) associates with the Eps8/Abi1/Sos1 complex and is recruited to the EGF receptor as part of a multiprotein signaling complex also involving She and Grb2. Increased expression of PI3KC2β stimulated Rac activity in A-431 epidermoid carcinoma cells, resulting in enhanced membrane ruffling and migration speed of the cells. Conversely, expression of dominant negative PI3KC2β reduced Rac activity, membrane ruffling, and cell migration. Moreover, PI3KC2β- overexpressing cells were protected from anoikis and displayed enhanced proliferation, independently of Rac function. Taken together, these findings suggest that PI3KC2β regulates the migration and survival of human tumor cells by distinct molecular mechanisms.

Original languageEnglish
Pages (from-to)3729-3744
Number of pages16
JournalMolecular Biology of the Cell
Volume17
Issue number9
DOIs
Publication statusPublished - Sep 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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    Katso, R. M., Pardo, O. E., Palamidessi, A., Franz, C. M., Marinov, M., De Laurentiis, A., Downward, J., Scita, G., Ridley, A. J., Waterfield, M. D., & Arcaro, A. (2006). Phosphoinositide 3-kinase C2β regulates cytoskeletal organization and cell migration via Rac-dependent mechanisms. Molecular Biology of the Cell, 17(9), 3729-3744. https://doi.org/10.1091/mbc.E05-11-1083