Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton.
Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton.
复制标题
磷酸肌醇3-激酶通过从肌动蛋白细胞骨架中动员醛糖酶调节糖酵解。
DOI：
10.1016/j.cell.2015.12.042
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发表时间：
2016-01-28
期刊：
影响因子：
64.5
通讯作者：
Wulf GM
中科院分区：
文献类型：
--
作者：
Hu H;Juvekar A;Lyssiotis CA;Lien EC;Albeck JG;Oh D;Varma G;Hung YP;Ullas S;Lauring J;Seth P;Lundquist MR;Tolan DR;Grant AK;Needleman DJ;Asara JM;Cantley LC;Wulf GM
磷酸肌醇 3-激酶 (PI3K) 途径调节葡萄糖代谢的多个步骤，还调节细胞骨架功能，例如细胞运动和附着。在这里，我们证明 PI3K 以不依赖 AKT 的方式直接协调糖酵解与细胞骨架动力学。生长因子或胰岛素刺激 Rac 的 PI3K 依赖性激活，导致肌动蛋白细胞骨架破坏、丝状肌动蛋白结合醛缩酶 A 的释放以及醛缩酶活性的增加。一致的是，PI3K 抑制剂会导致醛缩酶催化步骤中的糖酵解显着降低，而 AKT、SGK 或 mTOR 抑制剂则不会，而激活 PIK3CA 突变则会产生相反的效果。这些结果表明 PI3K 的主要调节功能整合了上皮细胞的代谢及其形式、形状和功能，协调糖酵解与肌动蛋白重塑的能量密集型动力学。
The Phosphoinositide 3-Kinase (PI3K) pathway regulates multiple steps in glucose metabolism but also cytoskeletal functions, such as cell movement and attachment. Here we show that PI3K directly coordinates glycolysis with cytoskeletal dynamics in an AKT-independent manner. Growth factors or insulin stimulate the PI3K-dependent activation of Rac, leading to disruption of the actin cytoskeleton, release of filamentous actin-bound aldolase A and an increase in aldolase activity. Consistently, PI3K-, but not AKT-, SGK- or mTOR-inhibitors, cause a significant decrease in glycolysis at the step catalyzed by aldolase, while activating PIK3CA mutations have the opposite effect. These results point towards a master regulatory function of PI3K that integrates an epithelial cell’s metabolism and its form, shape and function, coordinating glycolysis with the energy-intensive dynamics of actin remodeling.