Rac1-mediated membrane raft localization of PI3K/p110β is required for its activation by GPCRs or PTEN loss

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Rac1-mediated membrane raft localization of PI3K/p110β is required for its activation by GPCRs or PTEN loss

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Title: Rac1-mediated membrane raft localization of PI3K/p110β is required for its activation by GPCRs or PTEN loss
Author: Cizmecioglu, Onur; Ni, Jing; Xie, Shaozhen; Zhao, Jean J; Roberts, Thomas M

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Citation: Cizmecioglu, Onur, Jing Ni, Shaozhen Xie, Jean J Zhao, and Thomas M Roberts. 2016. “Rac1-mediated membrane raft localization of PI3K/p110β is required for its activation by GPCRs or PTEN loss.” eLife 5 (1): e17635. doi:10.7554/eLife.17635. http://dx.doi.org/10.7554/eLife.17635.
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Abstract: 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, p110α and p110β. We found that p110β 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 p110β to rafts alleviated the requirement for p110β-Rac1 association for GPCR signaling, cell growth and migration. In contrast, p110α, which does not play a physiological role in GPCR signaling, is found to reside in nonraft regions of the plasma membrane. Raft targeting of p110α allowed its EGFR-mediated activation by GPCRs. Notably, p110β 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 p110β. DOI: http://dx.doi.org/10.7554/eLife.17635.001
Published Version: doi:10.7554/eLife.17635
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050018/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29408304
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