Endothelin-converting enzyme-1 (ECE-1) is a type II membrane protein that cleaves big endothelin-1 (big ET-1) to endothelin-1 (ET-1). The role of the N-terminal and membrane-spanning signal anchor domains in the biosynthesis and function of ECE-1 isoforms, ECE-1a, ECE-1b and ECE-1c, remains unknown. This study provides evidence that the deletion of the cytoplasmic N-terminal tail (residues 1-55) of bovine ECE-1a results in the processing of a putative signal peptide located in the signal anchor domain leading to the partial secretion of the recombinant enzyme into the media. The truncation of N-terminal and/or signal anchor domain does not affect the activity of ECE-1a. These results indicate that the hydrophobic signal anchor domain alone is not sufficient for the membrane anchoring of ECE-1a and that the N-terminal domain of ECE-1a is important for membrane targeting as well as the intracellular localization of the enzyme.
Departments of *Biochemistry & Molecular Biology, University of Georgia, Athens, Georgia, and †Surgery, Medical University of South Carolina, Charleston, South Carolina, U.S.A.
Address correspondence and reprint requests to Dr Adviye Ergul, Department of Surgery, Medical University of South Carolina, 114 Doughty Street, Suite 625, P.O. Box 250778, Charleston, SC 29425, U.S.A.
© 2000 Lippincott Williams & Wilkins, Inc.