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

被引:153
|
作者
Scanga, SE
Ruel, L
Binari, RC
Snow, B
Stambolic, V
Bouchard, D
Peters, M
Calvieri, B
Mak, TW
Woodgett, JR
Manoukian, AS
机构
[1] Univ Toronto, Princess Margaret Hosp, Univ Hlth Network,Dept Med Biophys, Div Cell & Mol Biol,Ontario Canc Inst, Toronto, ON M5G 2M9, Canada
[2] Univ Toronto, Princess Margaret Hosp, Univ Hlth Network,Dept Med Biophys, Div Expt Therapeut,Ontario Canc Inst, Toronto, ON M5G 2M9, Canada
[3] Univ Toronto, Fac Med, Electron Microscopy Unit, Toronto, ON M5S 1A8, Canada
[4] Amgen Res Inst, Toronto, ON M5G 2C1, Canada
关键词
Drosophila; PKB; PI3K; PTEN; cell size; cell survival;
D O I
10.1038/sj.onc.1203739
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Akt (or PKB) is an oncogene involved in the regulation of cell survival. Akt is regulated by phosphatidylinositol 3-OH kinase (P13'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 me 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.
引用
收藏
页码:3971 / 3977
页数:7
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