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dc.contributor.authorCizmecioglu, Onuren_US
dc.contributor.authorNi, Jingen_US
dc.contributor.authorXie, Shaozhenen_US
dc.contributor.authorZhao, Jean Jen_US
dc.contributor.authorRoberts, Thomas Men_US
dc.date.accessioned2016-11-18T20:47:01Z
dc.date.issued2016en_US
dc.identifier.citationCizmecioglu, 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.en
dc.identifier.issn2050-084Xen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29408304
dc.description.abstractWe 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.17635.001en
dc.language.isoen_USen
dc.publishereLife Sciences Publications, Ltden
dc.relation.isversionofdoi:10.7554/eLife.17635en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050018/pdf/en
dash.licenseLAAen_US
dc.subjectPI3K signalingen
dc.subjectRac1en
dc.subjectPTEN lossen
dc.subjectGPCR signalingen
dc.subjectmembrane microdomainsen
dc.subjectHumanen
dc.subjectMouseen
dc.titleRac1-mediated membrane raft localization of PI3K/p110β is required for its activation by GPCRs or PTEN lossen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journaleLifeen
dash.depositing.authorCizmecioglu, Onuren_US
dc.date.available2016-11-18T20:47:01Z
dc.identifier.doi10.7554/eLife.17635*
dash.contributor.affiliatedCizmecioglu, Onur
dash.contributor.affiliatedXie, Shaozhen
dash.contributor.affiliatedNi, Jing
dash.contributor.affiliatedRoberts, Thomas
dash.contributor.affiliatedZhao, Jean


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