Quantitative phosphoproteomic analysis of the PI3K-regulated signaling network.
The PI3K pathway is commonly activated in cancer. Only a few studies have attempted to explore the spectrum of phosphorylation signaling downstream of the PI3K cascade. Such insight, however, is imperative to understand the mechanisms responsible for oncogenic phenotypes. By applying MS-based phosphoproteomics, we mapped 2509 phosphorylation sites on 1096 proteins, and quantified their responses to activation or inhibition of PIK3CA using isogenic knock-in derivatives and a series of targeted inhibitors. We uncovered phosphorylation changes in a wide variety of proteins involved in cell growth and proliferation, many of which have not been previously associated with PI3K signaling. A significant update of the posttranslational modification database PHOSIDA (http://www.phosida.com) allows efficient use of the data. All MS data have been deposited in the ProteomeXchange with identifier PXD003899 (http://proteomecentral.proteomexchange.org/dataset/PXD003899).
Department of Bioinformatics and Computational Biology, Genentech Inc, South San Francisco, CA, USA.
Florian
F
Gnad
Department of Translational Oncology, Genentech Inc, South San Francisco, CA, USA.
Jeffrey
J
Wallin
Department of Translational Oncology, Genentech Inc, South San Francisco, CA, USA.
Kyle
K
Edgar
Department of Protein Chemistry, Genentech Inc, South San Francisco, CA, USA.
Sophia
S
Doll
Department of Protein Chemistry, Genentech Inc, South San Francisco, CA, USA.
David
D
Arnott
Department of Translational Oncology, Genentech Inc, South San Francisco, CA, USA.
Liliane
L
Robillard
Department of Protein Chemistry, Genentech Inc, South San Francisco, CA, USA.
Donald S
DS
Kirkpatrick
Cell Signaling Technology, Inc, Danvers, MA, USA.
Matthew P
MP
Stokes
Department of Translational Oncology, Genentech Inc, South San Francisco, CA, USA.
Ulka
U
Vijapurkar
Department of Translational Oncology, Genentech Inc, South San Francisco, CA, USA.
Georgia
G
Hatzivassiliou
Department of Translational Oncology, Genentech Inc, South San Francisco, CA, USA.
Lori S
LS
Friedman
Department of Translational Oncology, Genentech Inc, South San Francisco, CA, USA.
Marcia
M
Belvin
D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D030541:Databases, Genetic; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020407:Internet; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction; D012984:Software
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
Cell Biology; PHOSIDA; PI3K; Phosphoproteomics; Signaling