Wittwer Franz, Jaquenoud Malika, Brogiolo Walter, Zarske Marcel, Wüstemann Philipp, Fernandez Rafael, Stocker Hugo, Wymann Matthias P, Hafen Ernst
Zoologisches Institut, Universität Zürich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland.
Dev Cell. 2005 Jun;8(6):817-27. doi: 10.1016/j.devcel.2005.04.002.
The Phosphatidylinositol-3 kinase/Protein Kinase B (PI3K/PKB) signaling pathway controls growth, metabolism, and lifespan in animals, and deregulation of its activity is associated with diabetes and cancer in humans. Here, we describe Susi, a coiled-coil domain protein that acts as a negative regulator of insulin signaling in Drosophila. Whereas loss of Susi function increases body size, overexpression of Susi reduces growth. We provide genetic evidence that Susi negatively regulates dPI3K activity. Susi directly binds to dP60, the regulatory subunit of dPI3K. Since Susi has no overt similarity to known inhibitors of PI3K/PKB signaling, it defines a novel mechanism by which this signaling cascade is kept in check. The fact that Susi is expressed in a circadian rhythm, with highest levels during the night, suggests that Susi attenuates insulin signaling during the fasting period.
磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/PKB）信号通路控制动物的生长、代谢和寿命，其活性失调与人类的糖尿病和癌症相关。在此，我们描述了Susi，一种卷曲螺旋结构域蛋白，它在果蝇中作为胰岛素信号的负调节因子发挥作用。Susi功能缺失会增加体型，而Susi过表达则会抑制生长。我们提供了遗传学证据，表明Susi负向调节dPI3K的活性。Susi直接与dPI3K的调节亚基dP60结合。由于Susi与PI3K/PKB信号通路的已知抑制剂没有明显相似性，它定义了一种控制该信号级联反应的新机制。Susi以昼夜节律表达，在夜间水平最高，这一事实表明Susi在禁食期减弱胰岛素信号。
