Temporal resolution of protein signaling (473.1)
Karen Anderson, Christal Dyane Sohl, BeiBei Luo, Shunyan Mo, Youngjoo Kim, Mihaela M. Apetri, Erin Denise Lew, Cristina M. Furdui, Joseph Schlessinger · The FASEB Journal · 2014
Receptor tyrosine kinases (RTKs) play an essential role by initiating multiple signaling pathways. Given their role in cellular processes such as cell proliferation, differentiation and migration, altered RTK activity has been associated with multiple developmental disorders and cancers. Early events in the initiation of a signaling pathway involve ligand binding, receptor dimerization, and autophosphorylation of specific tyrosine residues that in turn serve as binding sites for downstream signaling molecules. Dynamic control of multiple phosphorylation modifications of a single RTK can manifest critical control on multiple signal transduction pathways. An understanding of molecular mechanisms of these early dynamic events may hold the key to understanding and predicting the nature of oncogenic behavior and predicting the affects of RTK targeted therapy. Profiling using an integrated platform of technologies including electrospray ionization mass spectrometry (ESI‐MS) revealed a discrete, ordered pattern of tyrosine autophosphorylation with normal protein signaling. However this preferential order was lost with mutant forms of RTKs associated with oncogenesis. These molecular signatures provide a new understanding of the differences between normal and oncogenic forms of RTKs and an expanded functional understanding of the emerging therapeutic class of targeted kinase inhibitors.