Recombinant Mouse ECE-1 Protein, CF

Endothelin-converting enzymes (ECEs) hydrolyze a specific peptide bond of big endothelins to produce active endothelins, some of the most potent vasoconstrictors known (1). ECE-1 is a member of the M13 zinc metallopeptidase family. Other members of the M13 family include thermolysin, neprilysin, Kell, and ECE-2 (2). M13 metallopeptidases can be distinguished from other metallopeptidases by their sensitivity to inhibition by phosphoramidon. ECE-1 is most highly expressed in the cardiovascular endothelium, but is also expressed in some endocrine tissues (3). ECE-1 is known to hydrolyze a variety of bioactive peptides, including bradykinin, neurotensin, angiotensins, and Substance P, with a substrate specificity similar to that of neprilysin (4). ECE-1 displays pronounced pH dependence in its substrate specificity (5). The degradation of Substance P by ECE-1 in endosomes regulates beta-arrestin-dependent ERK-2 signaling to prevent cell death in some neuronal cells (6). Four isoforms of ECE-1 are present in humans and mice, all of which encode a Type II integral membrane protein (7). The four isoforms share a common extracellular catalytic domain, differing in their N-terminal cytoplasmic tail regions. The recombinant mouse ECE-1 transmembrane and cytoplasmic tail domains were replaced with a signal sequence, resulting in the secretion of the soluble catalytic ectodomain.