Encoding growth factor identity in the temporal dynamics of FoxO3 under the combinatorial control of ERK and AKT Kinases

Published: 1 August 2018| Version 3 | DOI: 10.17632/65fkdzt9x5.3
, Bernhard Steiert, Bernhard Kramer,
, John Albeck,


Sampattavanich et al., Cell Systems (2018) This data repository provides raw datasets for accompanying the paper, "Encoding growth factor identity in the temporal dynamics of FoxO3 under combinatorial regulation by ERK and Akt" by Sampattavanich et al., Cell Systems (2018) Synopsis: Forkhead box O3 transcription factor (FoxO3) functions as an integrative node for diverse upstream signaling networks, and has been implicated in a number of biological processes including cycle arrest, apoptosis, oxidative stress, cell migration and cell metabolism. Regulators of FoxO3, including phosphorylation, energy stress, genotoxic stress, and cytokines, control its abundance, subcellular localization and DNA-binding capacity. In this paper we study how the identities and concentrations of growth factors are encoded in the dynamics of FoxO3 activation. Transcription factors like FoxO3 often switch between on and off states repeatedly over the course of a 12-24 hours period. Immunoblotting and similar methods can obscure this switching behavior due to asynchronicity between cells. In contrast, our use of time-lapse microscopy of fluorescent reporter proteins reveals that FoxO3 exhibits complex low wavelength and pulsatile translocation dynamics responsive to combinatorial control by ERK and Akt with the potential to encode the identities and concentrations of multiple extracellular growth factors. Dataset Content: This dataset includes raw datasets either in .MAT, or .CSV for regenerating all figures in the publication. These folders should be placed inside the /rawdata folder in the git repository folder so that the reader can generate these figures on their own. /parentalVSreporter - This dataset is used to regenerate fig.1B, S1B and S1C. /Workspace - This dataset is important for all fPCA and pulse score analysis in Fig.1-6 /dualsensors - This dataset is used to regenerate Fig.6B /western - This dataset is used to regenerate Fig.1C and S1G /fixedcell - This dataset is used to regenerate Fig.7 /Time-lapse video - This folder gives video files of the main dataset for Fig.1-2, varying different growth factors at various dosing, with different drug pre-treatment. To learn more about this data, please also visit the accompanying HMS LINCS website shown below.


Steps to reproduce

Accompanying matlab scripts can also be found in the provided github link. To reproduce plots in the paper: 1. Clone the repo and install necessary toolbox 2. Create a new directory called 'rawdata' at the top-most level of the git repo folder 3. Download these files and place inside rawdata folder. Extract all zip files 4. Visit our github repository for instruction to regenerate each specific figures We also provide raw images and extracted data in LINCS-compatible CSV-format at HMS LINCS website.


Mahidol University Faculty of Medicine Siriraj Hospital, Harvard Medical School


Systems Biology, Proteomics, Biological Sciences Quantitative Methods