Presentation description

Dynamic changes in protein-protein interaction (PPI) networks underlie all physiological cellular functions and drive devastating human diseases, including cancer. However, methods to systematically map changes in PPI networks, and how these changes are relayed by post-translational modifications, are lacking. My project focused on integrating our in-house developed kinobead competition and correlation analysis (kiCCA) with global mass spectrometry (MS)-based phosphoproteomics to map how kinase-mediated protein phosphorylation controls PPI networks. To validate my approach, we used Hela cells that were stimulated with epidermal growth factor (EGF) as our model. We used kiCCA to map kinase PPls in both control and EGF-stimulated cells and used global phosphoproteomics to determine changes in protein phosphorylation. We then performed correlative analyses to determine if specific kinase-protein interactions are associated with a change in the phosphorylation state. This revealed known and novel kinase PPls that were associated with phosphorylation events. We foresee that our integrated proteomics approach can be used to systematically map dynamic kinase-substrate interaction networks in high-throughput, paving the way for a better, system-level understanding of cancer cell signaling.