AKT can be activated in the nucleus

Ruiwen Wang, Michael G. Brattain

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

To investigate issues about AKT/PKB nuclear localization in cells, we examined endogenous or transiently transfected AKT localization in cancer cell lines by immunofluorescence. We found that AKT can be detected in both the nucleus and cytoplasm of HEK 293, HeLa and MCF7E cells. It was found that an active process mediates AKT nuclear translocation as shown by fusing AKT with GFP3 protein. The cellular distribution pattern of serial deletion mutants from GFP3-HA-AKT revealed that more than one segment of AKT is required for AKT nuclear translocation, while the individual segment does not have any apparent nuclear transport activity. These results implied that the signal mediating AKT nuclear translocation is conformation dependent, or more likely, is dependent upon association with other proteins. It was also found that AKT does not contain any apparent nuclear export signal. Furthermore, we found that nuclear AKT was activated in MCF7E cells upon stimulation. The possibility that nuclear activated AKT was translocated from the cytoplasm was excluded through the generation of a chimeric AKT protein, in which a strong nuclear localization signal was fused to the C-terminal of AKT.

Original languageEnglish (US)
Pages (from-to)1722-1731
Number of pages10
JournalCellular Signalling
Volume18
Issue number10
DOIs
StatePublished - Oct 2006

Keywords

  • AKT
  • Activation
  • Nuclear localization
  • Nucleus

ASJC Scopus subject areas

  • Cell Biology

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