保守的PI3'K/PTEN/Akt信号通路在果蝇中调节细胞大小和存活。

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

作者信息

Scanga S E, Ruel L, Binari R C, Snow B, Stambolic V, Bouchard D, Peters M, Calvieri B, Mak T W, Woodgett J R, Manoukian A S

机构信息

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.

出版信息

Oncogene. 2000 Aug 17;19(35):3971-7. doi: 10.1038/sj.onc.1203739.

DOI:10.1038/sj.onc.1203739

PMID:10962553

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. Oncogene (2000) 19, 3971 - 3977.

摘要

Akt（或蛋白激酶B）是一种参与细胞存活调控的癌基因。Akt受磷脂酰肌醇3-羟基激酶（PI3'K）信号传导调控，并且已显示出通过PTEN肿瘤抑制因子缺失而过度激活。在果蝇中，使用果蝇IRS-4同源物（Chico）研究胰岛素信号传导已被证明是细胞大小的关键调节因子。我们研究了果蝇Akt（Dakt1），并表明它也参与细胞大小的调控。此外，我们进行了遗传上位性测试，以证明在果蝇中，PI3'K、PTEN和Akt构成了一个在发育的多个阶段被利用的信号盒。此外，我们表明这个信号盒也参与胚胎发生过程中的细胞存活调控。因此，这项研究确立了该信号通路在果蝇中的进化保守性。《癌基因》（2000年）19卷，3971 - 3977页。