BMP1/Tolloid-like substrates by iTRAQ degradomics

In this study, we used an iTRAQ-based quantitative proteomic approach to reveal the release of proteolytic fragments from the cell surface or the ECM by BMP-1. Thirty-seven extracellular proteins were found in significantly higher or lower amounts in the conditioned medium of HT1080 cells overexpressing BMP-1 and thus, could be considered as candidate substrates. Strikingly, three of these new candidates (betaglycan, CD109 and neuropilin-1) were TGF-Beta co-receptors, also acting as antagonists when released from the cell surface, and were chosen for further substrate validation.