Requirement for Akt-mediated survival in cell transformation by the dbl oncogene
In: Cellular Signalling, Jg. 19 (2007), Heft 1, S. 211-218
academicJournal
Zugriff:
Abstract: The dbl oncogene product is the founding member of a large family of oncogenic proteins that function by activating the small GTP-binding proteins Cdc42, Rac and Rho. Through its substrate GTPases, Dbl transduces proliferative signals from cell-surface receptors to diverse cellular effectors and signaling pathways. The mechanisms by which these multiple signals are integrated, as well as their relative contribution to Dbl-induced cell transformation, are presently poorly understood. We investigated the role of the survival regulators PI3-kinase and Akt in Dbl-induced cell transformation. We found that Dbl induced the phosphorylation of Akt on threonine 308, through the GTPases Rac and Cdc42 and in a PI3-kinase dependent manner. Pharmacological or biochemical interference with this pathway lead to a marked, dose-dependent inhibition of the focus formation activity exhibited by Dbl-expressing cells. Dbl expression stimulated the phosphorylation of the anti-apoptotic Akt substrate Bad, and caused a marked decrease in basal levels of apoptosis. Finally, we found that activated Cdc42 existed in cells in complex with phosphoionositide-dependent kinase-1 (PDK1), the downstream mediator of PI3-kinase action. The data indicate that Dbl signaling stimulate the formation of a novel survival complex, through which anti-apoptotic signals are generated and propagated. [Copyright &y& Elsevier]
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Requirement for Akt-mediated survival in cell transformation by the dbl oncogene
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Autor/in / Beteiligte Person: | Morley, S. ; Wagner, J. ; Kauppinen, K. ; Sherman, M. ; Manor, D. |
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Zeitschrift: | Cellular Signalling, Jg. 19 (2007), Heft 1, S. 211-218 |
Veröffentlichung: | 2007 |
Medientyp: | academicJournal |
ISSN: | 0898-6568 (print) |
DOI: | 10.1016/j.cellsig.2006.06.005 |
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