J Biol Chem 2021 Jan-Jun;296:100733. Epub 2021 May 4.
Physiology, Biophysics and Systems Biology Program, Weill Cornell Medicine, New York, New York, USA; Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, New York, USA; Institute for Advanced Study, Technical University of Munich, Garching, Germany; Department of Medicine, Weill Cornell Medicine, New York, New York, USA; Department of Biophysics, Physiology and Systems Biology, Weill Cornell Medicine, New York, New York, USA. Electronic address:
A disintegrin and metalloprotease 17 (ADAM17) is a cell-surface metalloprotease that serves as the principle sheddase for tumor necrosis factor α (TNFα), interleukin-6 receptor (IL-6R), and several ligands of the epidermal growth factor receptor (EGFR), regulating these crucial signaling pathways. ADAM17 activation requires its transmembrane domain, but not its cytoplasmic domain, and little is known about the role of this domain in vivo. To investigate, we used CRISPR-Cas9 to mutate the endogenous Adam17 locus in mice to produce a mutant ADAM17 lacking its cytoplasmic domain (Adam17Δcyto). Read More