期刊
ELIFE
卷 5, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.17635
关键词
-
类别
资金
- National Institutes of Health [P50 CA168504-01A1, P50 CA165962-01A1, CA172461-01, P01-CA50661, CA30002]
- Stand Up To Cancer Translational Research Grant [SU2C-AACR-DT0209]
We aimed to understand how spatial compartmentalization in the plasma membrane might contribute to the functions of the ubiquitous class IA phosphoinositide 3-kinase (PI3K) isoforms, p110 alpha and p110 beta. We found that p110 beta localizes to membrane rafts in a Rac1-dependent manner. This localization potentiates Akt activation by G-protein-coupled receptors (GPCRs). Thus genetic targeting of a Rac1 binding-deficient allele of p110 beta to rafts alleviated the requirement for p110 beta-Rac1 association for GPCR signaling, cell growth and migration. In contrast, p110 alpha, which does not play a physiological role in GPCR signaling, is found to reside in nonraft regions of the plasma membrane. Raft targeting of p110 alpha allowed its EGFR-mediated activation by GPCRs. Notably, p110 beta dependent, PTEN null tumor cells critically rely upon raft-associated PI3K activity. Collectively, our findings provide a mechanistic account of how membrane raft localization regulates differential activation of distinct PI3K isoforms and offer insight into why PTEN-deficient cancers depend on p110 beta.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据