Akt1 contains a functional leucine-rich nuclear export sequence.

Motoyasu Saji; Vasily Vasko; Faiza Kada; Elena Hardy Allbritton; Kenneth D Burman; Matthew D Ringel

doi:10.1016/j.bbrc.2005.04.109

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Akt1 contains a functional leucine-rich nuclear export sequence.

Motoyasu Saji·Vasily Vasko·Faiza Kada·Elena Hardy Allbritton·Kenneth D Burman·Matthew D Ringel

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Abstract

Nuclear Akt1 expression and Akt activation are common in cancer invasion. However, the mechanisms for this association and its causal role in invasion are uncertain. In an effort to identify potential mechanisms for regulating Akt subcellular localization, we analyzed the Akt gene sequences and identified a highly conserved leucine-rich potential nuclear export sequence (NES). Initial experiments demonstrated that leptomycin B induced nuclear Akt1 localization. Transient expression experiments demonstrated that, in comparison to wild-type Akt1, NES-mutated (AKT/NES) Akt1 has reduced interactions with CRM-1 and persistent nuclear localization. Subsequent stable transfection experiments in Akt1-/- fibroblasts confirmed that expression of AKT/NES resulted in persistent nuclear localization and activation1. Finally, stable expression of AKT/NES in Akt1-/- fibroblasts was sufficient to enhance cell migration in vitro. Thus, Akt1 contains a functional NES and mutation of the NES results in nuclear-predominant Akt1 activation that is sufficient to induce migration.

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Active Transport, Cell Nucleus Amino Acid Sequence Cell Line Cell Movement Cell Nucleus Enzyme Activation Humans Kidney Leucine Molecular Sequence Data Protein Serine-Threonine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt Structure-Activity Relationship Thyroid Neoplasms Journal Article Research Support, Non-U.S. Gov't

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Motoyasu Saji, Vasily Vasko, Faiza Kada, Elena Hardy Allbritton, Kenneth D Burman, Matthew D Ringel. 2005-06-24. Akt1 contains a functional leucine-rich nuclear export sequence.. https://doi.org/10.1016/j.bbrc.2005.04.109

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