Protein kinase C regulates the cell surface activity of endothelin-converting enzyme-1

Smith, Ian, Lew, Rebecca, Thomas, Walter G. and Tochon-Danguy, Nathalie (2006) Protein kinase C regulates the cell surface activity of endothelin-converting enzyme-1. International journal of peptide research and therapeutics, 12 3: 291-295. doi:10.1007/s10989-006-9034-3

Author Smith, Ian
Lew, Rebecca
Thomas, Walter G.
Tochon-Danguy, Nathalie
Title Protein kinase C regulates the cell surface activity of endothelin-converting enzyme-1
Journal name International journal of peptide research and therapeutics   Check publisher's open access policy
ISSN 1573-3904
Publication date 2006-09
Sub-type Article (original research)
DOI 10.1007/s10989-006-9034-3
Volume 12
Issue 3
Start page 291
End page 295
Total pages 5
Place of publication Netherlands
Publisher Springer
Language eng
Subject 270000 Biological Sciences
060602 Animal Physiology - Cell
060111 Signal Transduction
060110 Receptors and Membrane Biology
060199 Biochemistry and Cell Biology not elsewhere classified
060108 Protein Trafficking
110201 Cardiology (incl. Cardiovascular Diseases)
110903 Central Nervous System
Abstract The potent vasoconstrictor endothelin is a 21 amino acid peptide whose principal physiological function is to regulate vascular tone. The generation of endothelin is crucially dependent on the local presence and activity of endothelin converting enzyme-1 (ECE-1) expressed on the surface of vascular endothelial cells. In this study, we have shown in endothelial cells that the enzyme is phosphorylated, and that phosphorylation is increased by phorbol ester stimulation of protein kinase C (PKC). Furthermore, by monitoring specific ECE-1 activity on the surface of live cells, we also show that following PKC activation, enzyme activity is significantly increased at the cell surface, where it is positioned to catalyse the generation of active endothelin. We believe this novel finding is unprecedented for a peptide processing enzyme. Indeed, this new knowledge regarding the control of endothelin production by regulating ECE-1 activity at the cell surface opens up a new area of endothelin biology and will provide novel insights into the physiology and pathophysiology of endothelin and endothelin-associated diseases. In addition, the information generated in these studies may provide valuable new insights into potential extra- and intracellular targets for the pharmacological and perhaps even therapeutic regulation of endothelin production and thus vascular tone.
Keyword Endothelin converting enzyme 1 (ECE-1)
Subcellular distribution
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
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Created: Wed, 14 Jan 2009, 11:21:03 EST by Ms Julie Anne Hansen on behalf of School of Biomedical Sciences