Investigating RET RTK Signaling Pathways Using an IAP-Based Activity-Profiling Approach

Many neurodegenerative diseases,
such as Parkinson’s disease,
can be directly correlated with the deregulation in neuronal signaling.
Hence, it is indispensable for therapy development to understand the
participating signaling processes. Because the activity of the involved
protein kinases is of major interest for the investigation of these
signaling processes, an affinity-based chemical proteomics approach
that allows for the activity profiling of protein kinases was developed
within this study. This approach was applied to investigate the RET9
receptor tyrosine kinase signaling pathway that plays a central role
in neuronal signaling. In addition to already known RET9 downstream
targets, several other protein kinases were found to be highly activated
upon RET9 stimulation.