| Literature DB >> 26824656 |
Hai Hu1, Ashish Juvekar1, Costas A Lyssiotis2, Evan C Lien3, John G Albeck4, Doogie Oh5, Gopal Varma6, Yin Pun Hung7, Soumya Ullas8, Josh Lauring9, Pankaj Seth10, Mark R Lundquist2, Dean R Tolan11, Aaron K Grant6, Daniel J Needleman5, John M Asara12, Lewis C Cantley2, Gerburg M Wulf13.
Abstract
The phosphoinositide 3-kinase (PI3K) pathway regulates multiple steps in glucose metabolism and 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 inhibitors, 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 toward 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.Entities:
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Year: 2016 PMID： 26824656 PMCID： PMC4898774 DOI： 10.1016/j.cell.2015.12.042
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582