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PMID: 28059163 Published · epublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Phosphoproteomic comparison of Pik3ca and Pten signalling identifies the nucleotidase NT5C as a novel AKT substrate.

Scientific reports ·Vol. 7 ·2017-00-06 ·Pages 39985

Moniz LS, Surinova S, Ghazaly E, Velasco LG, Haider S, Rodríguez-Prados JC, Berenjeno IM, Chelala C, Vanhaesebroeck B

Abstract

To 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.

MeSH Terms
5'-Nucleotidase/metabolism Animals Cells, Cultured Class I Phosphatidylinositol 3-Kinases Gene Deletion Gene Expression Regulation Mice Mouse Embryonic Stem Cells Mutation PTEN Phosphohydrolase/genetics,metabolism Phosphatidylinositol 3-Kinases/genetics,metabolism Phosphoproteins/analysis Proteomics/methods Proto-Oncogene Proteins c-akt/metabolism Signal Transduction
Chemicals
Phosphoproteins Class I Phosphatidylinositol 3-Kinases Pik3ca protein, mouse Proto-Oncogene Proteins c-akt 5'-Nucleotidase PTEN Phosphohydrolase Pten protein, mouse
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Moniz Larissa S
UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street London WC1E 6DD, UK.
Surinova Silvia
UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street London WC1E 6DD, UK.
Ghazaly Essam
Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Velasco Lorena Gonzalez
UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street London WC1E 6DD, UK.
Haider Syed
Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Rodríguez-Prados Juan Carlos
Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Berenjeno Inma M
UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street London WC1E 6DD, UK.
Chelala Claude
Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Vanhaesebroeck Bart
UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street London WC1E 6DD, UK.
Conflict of Interest

B.V. is a consultant to Karus Therapeutics (Oxford, UK).

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Article Info
Journal
Scientific reports
Abbr.
Sci Rep
ISSN
2045-2322
DOI
10.1038/srep39985
Published
2017-00-06
Epub
2017-00-06
Pages
39985
Language
English
Region
England
NLM ID
101563288
PMCID
PMC5216349
Subset
IM
Grants
Medical Research Council · G0800914 · United Kingdom
Cancer Research UK · C23338/A15965 · United Kingdom
External Links
PubMed source DOI: 10.1038/srep39985 PMC Full Text View journal details
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