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dc.contributor.authorMoniz, LSen_US
dc.contributor.authorSurinova, Sen_US
dc.contributor.authorGhazaly, Een_US
dc.contributor.authorVelasco, LGen_US
dc.contributor.authorHaider, Sen_US
dc.contributor.authorRodríguez-Prados, JCen_US
dc.contributor.authorBerenjeno, IMen_US
dc.contributor.authorChelala, Cen_US
dc.contributor.authorVanhaesebroeck, Ben_US
dc.description.abstractTo identify novel effectors and processes regulated by PI3K pathway activation, we performed an unbiased phosphoproteomic screen comparing two common events of PI3K deregulation in cancer: oncogenic Pik3ca mutation (Pik3caH1047R) and deletion of Pten. Using mouse embryonic fibroblast (MEF) models that generate inducible, low-level pathway activation as observed in cancer, we quantified 7566 unique phosphopeptides from 3279 proteins. A number of proteins were found to be differentially-regulated by Pik3caH1047R and Pten loss, suggesting unique roles for these two events in processes such as vesicular trafficking, DNA damage repair and RNA splicing. We also identified novel PI3K effectors that were commonly-regulated, including putative AKT substrates. Validation of one of these hits, confirmed NT5C (5',3'-Nucleotidase, Cytosolic) as a novel AKT substrate, with an unexpected role in actin cytoskeleton regulation via an interaction with the ARP2/3 complex. This study has produced a comprehensive data resource and identified a new link between PI3K pathway activation and actin regulation.en_US
dc.description.sponsorshipCancer Research UK (C23338/A15965, to BV), UK NIHR University College London Hospitals Biomedical Research Centre (to BV), the Medical Research Council (G0800914, to BV) and Barts and the London Charity (297/298, to BV), the Cancer Research UK–UCL Centre (SS) and The Barry Reed Cancer Research Fund (EG).en_US
dc.format.extent39985 - ?en_US
dc.relation.ispartofSci Repen_US
dc.subjectCells, Cultureden_US
dc.subjectGene Deletionen_US
dc.subjectGene Expression Regulationen_US
dc.subjectMouse Embryonic Stem Cellsen_US
dc.subjectPTEN Phosphohydrolaseen_US
dc.subjectPhosphatidylinositol 3-Kinasesen_US
dc.subjectProto-Oncogene Proteins c-akten_US
dc.subjectSignal Transductionen_US
dc.titlePhosphoproteomic comparison of Pik3ca and Pten signalling identifies the nucleotidase NT5C as a novel AKT substrate.en_US
pubs.notesNot knownen_US
pubs.publication-statusPublished onlineen_US

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