Functional significance of the isoforms of endothelin-converting enzyme-1

The subcellular localization of endothelin-converting enzyme-1 (ECE-1) is a matter of some controversy, further complicated by the discovery of its mu ltiple isoforms. ECE-1 is a critical enzyme in the biosynthesis of the pote nt vasoconstrictor peptide endothelin (ET), and, as such, represents a pote ntial target for drug therapy in the control of disease states involving th e ET system. Knowledge of the precise locations of the isoforms and their r egulation would aid in the design of drugs to target specifically ECE-1. In this study, the subcellular localization and potential targeting pathways of the ECE-1 isoforms were investigated. Antipeptide antibodies were raised to the unique N-terminal sequence of ECE-1b and were then used in the inve stigation of its subcellular distribution. Mutagenesis of proposed targetin g sequences within the cytoplasmic tails of the isoforms was carried out to determine their significance in subcellular localization.