The conserved pi3′k/pten/akt signaling pathway regulates both cell size and survival in drosophila

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_. Access through

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BEING VIEWED BY OTHERS GOLPH3 PROTEIN CONTROLS ORGAN GROWTH BY INTERACTING WITH TOR SIGNALING PROTEINS IN DROSOPHILA Article Open access 27 November 2022 SUPPRESSION OF PATRONIN DEFICIENCY

BY ALTERED HIPPO SIGNALING IN _DROSOPHILA_ ORGAN DEVELOPMENT Article 31 July 2020 IDENTIFICATION OF THE WALLENDA JNKKK AS AN ALK SUPPRESSOR REVEALS INCREASED COMPETITIVENESS OF

ALK-EXPRESSING CELLS Article Open access 11 September 2020 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:

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references 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).

AUTHOR INFORMATION Author notes * Sam E Scanga and Laurent Ruel: The first two authors contributed equally to this work AUTHORS AND AFFILIATIONS * 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 * 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 * Amgen Research Institute, 620 University

Avenue, Toronto, M5G 2C1, Ontario, Canada Brian Snow, Vuk Stambolic, Denis Bouchard, Malte Peters & Tak W Mak * Electron Microscopy Unit, Medical Sciences Building, Faculty of Medicine,

University of Toronto, 8 Taddle Creek Road, Toronto, M5S 1A8, Ontario, Canada Batista Calvieri Authors * Sam E Scanga View author publications You can also search for this author inPubMed 

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also search for this author inPubMed Google Scholar * Batista Calvieri View author publications You can also search for this author inPubMed Google Scholar * Tak W Mak View author

publications You can also search for this author inPubMed Google Scholar * James R Woodgett View author publications You can also search for this author inPubMed Google Scholar * Armen S

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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 Download citation * Received: 25 April 2000 * Revised: 12 June 2000 * Accepted: 13 June 2000 * Published: 17 August 2000 * Issue Date: 17 August 2000 *

DOI: https://doi.org/10.1038/sj.onc.1203739 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not

currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * _Drosophila_ * PKB * PI3K * PTEN * cell size * cell

survival