Abstract 5203: Domains that distinguish Akt1 from Akt2 in cell migration
| Autor: | Sharmila Bharathi Natarajan, Guo-Lei Zhou, Jeffrey Field |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | Cancer Research. 70:5203-5203 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am10-5203 |
| Popis: | Domains that distinguish Akt1 from Akt2 in cell migration Sharmila B. Natarajan, Guo-Lei Zhou and Jeffrey Field Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 The Akt family of kinases, Akt1, Akt2 and Akt3 are activated in many cancers where they play critical role in cell survival, metabolism and migration. There are distinctive roles for Akt1 and Akt2 in cell migration where, depending on the cell type, loss of Akt1 can either stimulate or inhibit cell migration. Previous work from our lab demonstrated that loss of Akt2 stimulated cell motility and that, based on chimeras, the kinase domains of Akt1 and Akt2 are interchangeable. Specificity is conferred by the PH domain and a linker domain that separates the PH domain from the kinase domain. To address regions that are required to rescue Akt1 knockouts, which have reduced cell motility, we performed rescue experiments with mouse embryo fibroblasts from Akt1 knockout mice. Our results are in concordance with a study by E. K. Kim et al., (Cell Signaling, 2008) where they found that the linker region is again likely to confer specificity. Importantly, we found that a new construct, in which only the linker domain of Akt1 was swapped into Akt2, stimulated cell migration of Akt1 knockouts. Additionally, we find that both Akt1 and Akt2 associate with the Pak protein kinase but through different mechanisms. These studies suggest that differences in interaction with Pak may underlie the opposing effects of Akt1 and Akt2 on cell migration. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5203. |
| Databáze: | OpenAIRE |
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