Phosphoproteomic studies of receptor tyrosine kinases: future perspectives

Abstract

In the last decade, large-scale mass spectrometry-based phosphoproteomic studies of receptor tyrosine kinases (RTKs) have generated a compendium of signalling networks that are activated downstream of these receptors. In this article, a brief summary of previous phosphoproteomic studies on epidermal growth factor receptor (EGFR) signalling will be presented together with a perspective on the importance for the field to keep pace with new advances in RTK biology. Using examples drawn primarily from studies on the EGFR, c-Met and Flt3 receptors, areas in RTK biology which will greatly benefit from the power of phosphoproteomics will be discussed, including (a) validating oncogenic RTK mutants identified in cancer genome sequencing efforts, (b) spatial RTK signalling networks and (c) understanding crosstalk and co-activation between members of the RTK superfamily.