Phosphorylation of iRhom2 Controls Stimulated Proteolytic Shedding by the Metalloprotease ADAM17/TACE

• DOI: 10.1016/j.celrep.2017.09.074
• Publication Date: 2017-10-17T12:33:30Z
• Authors: Miguel Cavadas; Ioanna Oikonomidi; Catarina J. Gaspar; Emma Burbridge; Marina Badenes; Inês Félix; Alfonso Bolado; Tianyi Hu; Andrea Bileck; Christopher Gerner; Pedro M. Domingos; Alex von Kriegsheim; Colin Adrain
• Keywords: Immunoprecipitation

Cell surface metalloproteases coordinate signaling during development, tissue homeostasis, and disease. TACE (TNF-α-converting enzyme), is responsible for cleavage ("shedding") of membrane-tethered molecules, including the cytokine TNF, activating ligands EGFR. The trafficking within secretory pathway requires its binding to iRhom2, which mediates exit from endoplasmic reticulum. An important, but mechanistically unclear, feature biology ability be stimulated rapidly on cell by numerous inflammatory growth-promoting agents. Here, we report a role iRhom2 in stimulation surface. shedding stimuli trigger MAP kinase-dependent phosphorylation N-terminal cytoplasmic tail. This recruits 14-3-3 proteins, enforcing dissociation complexes with promoting substrates. Our data reveal that controls multiple aspects biology,