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Nuclear/cytoplasmic localization of Akt activity in the cell cycle

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Summary.

The serine/threonine protein kinase Akt (also known as PKB) is a proto-oncogene and one of the most frequently hyperactivated kinases in human cancer. Its activation downstream of growth-factor-stimulated phosphatidylinositide-3′-OH kinase activity plays a role in the control of cell cycle, cell growth, apoptosis and cell energy metabolism. Akt phosphorylates some thousand downstream substrates, including typical cytoplasmic as well as nuclear proteins. Accordingly, it is not surprising that Akt activity can be found in both, the cytoplasm and the nucleus. Here we report the cell cycle regulation of nuclear and cytoplasmic Akt activity in mammalian cells. These data provide new insights into the regulation of Akt activity and have implications for future studies on the regulation of the wide variety of different nuclear and cytoplasmic Akt substrates.

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References

  • A Astrinidis EP Henske (2005) ArticleTitleTuberous sclerosis complex: linking growth and energy signaling pathways with human disease Oncogene 24 7475–7481 Occurrence Handle16288294 Occurrence Handle10.1038/sj.onc.1209090 Occurrence Handle1:CAS:528:DC%2BD2MXht1Wis7vL

    Article  PubMed  CAS  Google Scholar 

  • RA Bachmann J-H Kim A-L Wu I-H Park J Chen (2006) ArticleTitleA nuclear transport signal in mammalian target of rapamycin is critical for its cytoplasmic signaling to S6 kinase 1 J Biol Chem 281 7357–7363 Occurrence Handle16407298 Occurrence Handle10.1074/jbc.M512218200 Occurrence Handle1:CAS:528:DC%2BD28Xit1ygtrY%3D

    Article  PubMed  CAS  Google Scholar 

  • MN Corradetti K-L Guan (2006) ArticleTitleUpstream of the mammalian target of rapamycin: do all roads pass through mTOR? Oncogene 25 6347–6360 Occurrence Handle17041621 Occurrence Handle10.1038/sj.onc.1209885 Occurrence Handle1:CAS:528:DC%2BD28XhtVOlsrrM

    Article  PubMed  CAS  Google Scholar 

  • J Dostie F Lejbkowicz N Sonenberg (2000) ArticleTitleNuclear eukaryotic initiation factor 4E (eIF4E) colocalizes with splicing factors in speckles J Cell Biol 148 239–247 Occurrence Handle10648556 Occurrence Handle10.1083/jcb.148.2.239 Occurrence Handle1:CAS:528:DC%2BD3cXot1ekug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • N Fujita S Sato K Katayama T Tsuruo (2002) ArticleTitleAkt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization J Biol Chem 277 28706–28713 Occurrence Handle12042314 Occurrence Handle10.1074/jbc.M203668200 Occurrence Handle1:CAS:528:DC%2BD38XmsVGqtbw%3D

    Article  PubMed  CAS  Google Scholar 

  • F Furuya JA Hanover S-Y Cheng (2006) ArticleTitleActivation of phosphatidylinositol 3-kinase signaling by a mutant thyroid hormone β receptor Proc Natl Acad Sci USA 103 1780–1785 Occurrence Handle16446424 Occurrence Handle10.1073/pnas.0510849103 Occurrence Handle1:CAS:528:DC%2BD28Xhslehtrk%3D

    Article  PubMed  CAS  Google Scholar 

  • JE Kim J Chen (2000) ArticleTitleCytoplasmic-nuclear shuttling of FKBP12-rapamycin-associated protein is involved in rapamycin-sensitive signaling and translation initiation Proc Natl Acad Sci USA 97 14340–14345 Occurrence Handle11114166 Occurrence Handle10.1073/pnas.011511898 Occurrence Handle1:CAS:528:DC%2BD3MXitVCluw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • F Lejbkowicz C Goyer A Darveau S Neron R Lemieux N Sonenberg (1992) ArticleTitleA fraction of the mRNA 5′cap-binding protein, eukaryotic initiation factor 4E, localizes to the nucleus Proc Natl Acad Sci USA 89 9612–9616 Occurrence Handle1384058 Occurrence Handle10.1073/pnas.89.20.9612 Occurrence Handle1:CAS:528:DyaK3sXhvFOquw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • J Liang J Zubovitz T Petrocelli R Kotchetkov MK Connor K Han JH Lee S Ciarallo C Catzavelos R Beniston E Franssen JM Slingerland (2002) ArticleTitlePKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest Nat Med 8 1153–1160 Occurrence Handle12244302 Occurrence Handle10.1038/nm761 Occurrence Handle1:CAS:528:DC%2BD38XnsVGrt7s%3D

    Article  PubMed  CAS  Google Scholar 

  • D Lou N Griffith DJ Noonan (2001) ArticleTitleThe tuberous sclerosis 2 gene product can localize to nuclei in a phosphorylation-dependent manner Mol Cell Biol Res Commun 4 374–380 Occurrence Handle11703097 Occurrence Handle10.1006/mcbr.2001.0307 Occurrence Handle1:CAS:528:DC%2BD38XptVGj

    Article  PubMed  CAS  Google Scholar 

  • AM Martelli M Nyakern G Tabellini R Bortul PL Tazzari C Evangelisti L Cocco (2006) ArticleTitlePhosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia Leukemia 20 911–928 Occurrence Handle16642045 Occurrence Handle10.1038/sj.leu.2404245 Occurrence Handle1:CAS:528:DC%2BD28XkvVylsr4%3D

    Article  PubMed  CAS  Google Scholar 

  • A Miloloza M Rosner M Nellist D Halley G Bernaschek M Hengstschläger (2000) ArticleTitleThe TSC1 gene product, hamartin, negatively regulates cell proliferation Hum Mol Genet 9 1721–1727 Occurrence Handle10915759 Occurrence Handle10.1093/hmg/9.12.1721 Occurrence Handle1:CAS:528:DC%2BD3cXlsFOqtbc%3D

    Article  PubMed  CAS  Google Scholar 

  • D Pan J Dong Y Zhang X Gao (2004) ArticleTitleTuberous sclerosis complex: from Drosophila to human disease Trends Cell Biol 14 78–85 Occurrence Handle15102439 Occurrence Handle10.1016/j.tcb.2003.12.006 Occurrence Handle1:CAS:528:DC%2BD2cXhtVOrtL8%3D

    Article  PubMed  CAS  Google Scholar 

  • M Rosner M Hengstschläger (2004) ArticleTitleTuberin binds p27 and negatively regulates its interaction with the SCF component Skp2 J Biol Chem 279 48707–48715 Occurrence Handle15355997 Occurrence Handle10.1074/jbc.M405528200 Occurrence Handle1:CAS:528:DC%2BD2cXpslGqtLc%3D

    Article  PubMed  CAS  Google Scholar 

  • M Rosner A Freilinger M Hengstschläger (2004) ArticleTitleProteins interacting with the tuberous sclerosis gene products Amino Acids 27 119–128 Occurrence Handle15351877 Occurrence Handle10.1007/s00726-004-0119-z Occurrence Handle1:CAS:528:DC%2BD2cXoslGisLs%3D

    Article  PubMed  CAS  Google Scholar 

  • M Rosner A Freilinger M Hengstschläger (2007) ArticleTitleAkt regulates nuclear/cytoplasmic localization of tuberin Oncogene 26 521–531 Occurrence Handle16862180 Occurrence Handle10.1038/sj.onc.1209812 Occurrence Handle1:CAS:528:DC%2BD2sXos12qtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • I Shin FM Yakes F Rojo NY Shin AV Bakin J Baselga CL Arteaga (2002) ArticleTitlePKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization Nat Med 8 1145–1152 Occurrence Handle12244301 Occurrence Handle10.1038/nm759 Occurrence Handle1:CAS:528:DC%2BD38XnsVGrt70%3D

    Article  PubMed  CAS  Google Scholar 

  • T Soucek O Pusch R Wienecke JE DeClue M Hengstschläger (1997) ArticleTitleRole of the tuberous sclerosis gene-2 product in cell cycle control J Biol Chem 272 29301–29308 Occurrence Handle9361010 Occurrence Handle10.1074/jbc.272.46.29301 Occurrence Handle1:CAS:528:DyaK2sXnsVOgtLs%3D

    Article  PubMed  CAS  Google Scholar 

  • G Viglietto ML Motti P Bruni RM Melillo A D’Alessio D Califano F Vinci G Chiappetta P Tsichlis A Bellacosa A Fusco M Santoro (2002) ArticleTitleCytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer Nat Med 8 1136–1144 Occurrence Handle12244303 Occurrence Handle10.1038/nm762 Occurrence Handle1:CAS:528:DC%2BD38XnsVGrt7g%3D

    Article  PubMed  CAS  Google Scholar 

  • R Wienecke JC Maize F Shoarinejad WC Vass J Reed JS Binfacino JII Resau J de Gunzburg RS Yeung JE DeClue (1996) ArticleTitleCo-localization of the TSC2 product tuberin with its target Rap1 in the Golgi apparatus Oncogene 13 913–923 Occurrence Handle8806680 Occurrence Handle1:CAS:528:DyaK28XmtFans74%3D

    PubMed  CAS  Google Scholar 

  • S Wullschleger R Loewith MN Hall (2006) ArticleTitleTOR signaling in growth and metabolism Cell 124 471–484 Occurrence Handle16469695 Occurrence Handle10.1016/j.cell.2006.01.016 Occurrence Handle1:CAS:528:DC%2BD28Xhslaqs74%3D

    Article  PubMed  CAS  Google Scholar 

  • X Zhang L Shu H Hosoi KG Murti PJ Houghton (2002) ArticleTitlePredominant nuclear localization of mammalian target of rapamycin in normal and malignant cells in culture J Biol Chem 277 28127–28134 Occurrence Handle12000755 Occurrence Handle10.1074/jbc.M202625200 Occurrence Handle1:CAS:528:DC%2BD38XlvFKgurw%3D

    Article  PubMed  CAS  Google Scholar 

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Rosner, M., Hanneder, M., Freilinger, A. et al. Nuclear/cytoplasmic localization of Akt activity in the cell cycle. Amino Acids 32, 341–345 (2007). https://doi.org/10.1007/s00726-007-0509-0

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  • DOI: https://doi.org/10.1007/s00726-007-0509-0

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