¹Department 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, Ontario, Canada, M5G 2M9

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

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

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

Correspondence to: A S Manoukian, 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, Ontario, Canada, M5G 2M9

^aSam E Scanga and Laurent Ruel contributed equally to this work

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. Oncogene (2000) 19, 3971-3977

Drosophila; PKB; PI3K; PTEN; cell size; cell survival

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