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  • Original Paper
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The conserved PI3′K/PTEN/Akt signaling pathway regulates both cell size and survival in Drosophila

Oncogene volume 19, pages 3971–3977 (2000)Cite this article

Abstract

Akt (or PKB) is an oncogene involved in the regulation of cell survival. Akt is regulated by phosphatidylinositol 3-OH kinase (PI3′K) signaling and has shown to be hyperactivated through the loss of the PTEN tumor suppressor. In Drosophila, insulin signaling as studied using the Drosophila IRS-4 homolog (Chico) has been shown to be a crucial regulator of cell size. We have studied Drosophila Akt (Dakt1) and have shown that it is also involved in the regulation of cell size. Furthermore we have performed genetic epistasis tests to demonstrate that in Drosophila, PI3′K, PTEN and Akt comprise a signaling cassette that is utilized during multiple stages of development. In addition, we show that this signaling cassette is also involved in the regulation of cell survival during embryogenesis. This study therefore establishes the evolutionary conservation of this signaling pathway in Drosophila.

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Abbreviations

PKB:

Protein Kinase B

PI3′K:

phosphatidylinositol 3-OH kinase

IRS:

insulin receptor substrate

Dakt1 :

Drosophila Akt

DPTEN:

Drosophila PTEN

Dp110 :

Drosophila PI3′K catalytic subunit

TUNEL:

TdT-mediated dUTP nick end labeling

AO:

Acridine orange

D-Akt:

Dakt1 protein

His-D-Akt:

Hexahistidine tagged D-Akt

cl-8:

Clone 8 Drosophila imaginal disc cell line

HsDakt :

Heat shock promoter Dakt1 cDNA transgene

y :

Drosophila yellow gene

FACS:

fluorescence-activated cell sorter

FSC:

Forward Scatter

SEM:

Scanning electron microscopy

DIG:

digoxigenin

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Acknowledgements

We thank S Leevers for UAS Dp110 and UAS Dp110D954A DNA and fly lines. We thank J Abrams for grim and reaper cDNAs. We also thank N Anthopoulos for help with the figures. This work was supported by a grant from the National Cancer Institute of Canada (AS Manoukian and JR Woodgett) and by a Howard Hughes Medical Institute award (JR Woodgett).

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Author notes

  1. Sam E Scanga and Laurent Ruel: The first two authors contributed equally to this work

Authors and Affiliations

  1. Department of Medical Biophysics, Division of Cell and Molecular Biology, Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, 610 University Avenue, Toronto, M5G 2M9, Ontario, Canada

    Sam E Scanga, Richard C Binari & Armen S Manoukian

  2. Department of Medical Biophysics, Division of Experimental Therapeutics, Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, 610 University Avenue, Toronto, M5G 2M9, Ontario, Canada

    Laurent Ruel & James R Woodgett

  3. Amgen Research Institute, 620 University Avenue, Toronto, M5G 2C1, Ontario, Canada

    Brian Snow, Vuk Stambolic, Denis Bouchard, Malte Peters & Tak W Mak

  4. Electron Microscopy Unit, Medical Sciences Building, Faculty of Medicine, University of Toronto, 8 Taddle Creek Road, Toronto, M5S 1A8, Ontario, Canada

    Batista Calvieri

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  1. Sam E Scanga
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Scanga, S., Ruel, L., Binari, R. et al. The conserved PI3′K/PTEN/Akt signaling pathway regulates both cell size and survival in Drosophila. Oncogene 19, 3971–3977 (2000). https://doi.org/10.1038/sj.onc.1203739

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