Updated publication reference for PubMed record(s): 31585087. Updated publication reference for DOI(s): https://doi.org/10.1016/j.cell.2019.09.008. Receptor tyrosine kinases (RTKs) are membrane proteins that regulate complex, multilayered signaling networks centered on tyrosine phosphorylation of proteins with broad implications in human health and disease. Here we developed a large-scale mass spectrometry-based proteomics platform for investigation of in-vivo RTK signaling networks and the dynamic protein interactions they induce.