The conserved PI3'K/PTEN/Akt signaling pathway regulates both cell size and survival in Drosophila.
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.
Scanga
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SE
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.
Ruel
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L
Binari
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RC
Snow
B
B
Stambolic
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V
Bouchard
D
D
Peters
M
M
Calvieri
B
B
Mak
T W
TW
Woodgett
J R
JR
Manoukian
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AS
D000818:Animals; D048429:Cell Size; D002470:Cell Survival; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D004843:Epistasis, Genetic; D005123:Eye / Q000196:embryology; D005260:Female; D017344:Genes, Insect; D019476:Insect Proteins / Q000502:physiology*; D007328:Insulin / Q000502:physiology*; D008297:Male; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D025521:Tumor Suppressor Proteins
D029721:Drosophila Proteins; D019476:Insect Proteins; D007328:Insulin; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D010744:Phosphoric Monoester Hydrolases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D025521:Tumor Suppressor Proteins; C494917:Akt1 protein, Drosophila