Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy


Authors:
Jonathan So, Adrian Pasculescu, Anna Y. Dai1, Kelly Williton, Andrew James, Vivian Nguyen, Pau Creixell, Erwin M. Schoof, John Sinclair, Miriam Barrios-Rodiles, Jun Gu, Aldis Krizus, Ryan Williams, Marina Olhovsky, James W. Dennis, Jeffrey L. Wrana, Rune Linding, Claus Jorgensen, Tony Pawson, Karen Colwill
Sci Signal. 2015 Apr 7;8(371):rs3. doi: 10.1126/scisignal.2005700.
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Phenotype Summary

Click any piechart for all phenotype response details
RNAi and cDNA combined

Phenotype measured as cleaved CASP3
apoptotic response to TRAIL stimulation.

Phenotype measured as cleaved CASP3 and PARP
apoptotic response to TRAIL stimulation.

Sensitizer: positive (+) correlation of apoptotic response with kinase expression level ;
Resistor: negative (-) correlation of apoptotic response with kinase expression level;
Neutral: no correlation to kinase expression level;
Unclassified: not enough data for classification;

cDNA Immunoprecipitation-Mass Spectrometry (IP-MS) Summary


Identified Kinase Partners
     
Identified Phosphorylation Sites during IP-MS

Phosphorylation Dynamics during TRAIL Stimulation (0, 5min, 60min)


Quantified Phosphorylation Sites
and Predicted Kinases and SH2-based readers



Information flow in TRAIL-induced apoptosis networks


Information Flow network and optimal routes at t=0 min, t=5 min and t=60 min
            
Differential Information Flow details