| First Author | Cizmecioglu O | Year | 2016 |
| Journal | Elife | Volume | 5 |
| PubMed ID | 27700986 | Mgi Jnum | J:238639 |
| Mgi Id | MGI:5823304 | Doi | 10.7554/eLife.17635 |
| Citation | Cizmecioglu O, et al. (2016) Rac1-mediated membrane raft localization of PI3K/p110beta is required for its activation by GPCRs or PTEN loss. Elife 5:e17635 |
| abstractText | 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, p110alpha and p110beta. We found that p110beta 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 p110beta to rafts alleviated the requirement for p110beta-Rac1 association for GPCR signaling, cell growth and migration. In contrast, p110alpha, which does not play a physiological role in GPCR signaling, is found to reside in nonraft regions of the plasma membrane. Raft targeting of p110alpha allowed its EGFR-mediated activation by GPCRs. Notably, p110beta 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 p110beta. |
