A Network Approach to Human Kinase Specificity

In combined experimental and computational approaches, we want to elucidate the role of post-translational protein modifications, such as phosphorylation, for dynamic cellular processes and investigating how the large number of changing PTMs is coordinated in cellular protein networks and likewise how PTMs may modulate protein-protein interaction networks.

 

The global analysis of post-translational modification and phosphorylation-dependent interactions indicate coordinated targeting of specific molecular functions via PTMs at different levels emphasizing a protein network approach as requisite to better understand modification impact on cellular signaling. For example, local linear phosphor-motif information can be augmented with network context of kinases and phospho-proteins to substantially increase specificity in substrate-kinase assignments. We present novel approaches to enhance network based predictions of kinase-substrate relationships.

 

Network approaches are about to strongly shape our view on how specificity is achieved in cellular signal transduction and post-transcriptional regulation and may ultimately reveal the molecular changes in cellular processes that occur in human diseases such as cancer.