Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1994-08-10
1997-11-18
Jones, W. Gary
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435 24, 435 29, 435 691, 4351723, 4352523, C12N 1563, C12Q 168
Patent
active
056886403
ABSTRACT:
Endothelin-1 (ET-1), a 21-residue vasoactive peptide, is produced in vascular endothelial cells from the 38-residue inactive intermediate, big endothelin-1 via a specific cleavage at Trp21-Val22. The protease that catalyzes the conversion, endothelin converting enzyme (ECE), constitutes a potential regulatory site for the production of the active peptide. Disclosed herein is the identification of ECE-1, a novel membrane-bound neutral Zn.sup.2+ metalloprotease that is expressed abundantly in endothelial cells in vivo, and structurally related to neutral endopeptidase 24.11 and Kell blood group protein. When transfected into cultured cells that normally secrete only big ET-1, the ECE-1 cDNA conferred the ability to secrete mature ET-1. In transfected cells, ECE-1 processes endogenously synthesized big ET-1 as well as exogenously supplied big ET-1, which interacts with ECE-1 on the cell surface. The remarkable specificity of ECE-1 provides a target for selective pharmacological intervention to alter ET-1 production in certain clinical disorders.
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Board of Regents , The University of Texas System
Jones W. Gary
Tran Paul B.
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