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.

中文翻译：

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蛋白激酶 C 调节内皮素转化酶 1 的细胞表面活性。

有效的血管收缩内皮素是一种 21 个氨基酸的肽，其主要生理功能是调节血管张力。内皮素的产生主要取决于血管内皮细胞表面表达的内皮素转化酶-1 (ECE-1) 的局部存在和活性。在这项研究中，我们在内皮细胞中显示该酶被磷酸化，并且磷酸化通过蛋白激酶 C (PKC) 的佛波酯刺激而增加。此外，通过监测活细胞表面的特定 ECE-1 活性，我们还表明，在 PKC 激活后，细胞表面的酶活性显着增加，在那里它被定位为催化活性内皮素的产生。我们相信这一新发现对于肽加工酶来说是前所未有的。的确，这种通过调节细胞表面 ECE-1 活性来控制内皮素产生的新知识开辟了内皮素生物学的新领域，并将为内皮素和内皮素相关疾病的生理学和病理生理学提供新的见解。此外，这些研究中产生的信息可能为潜在的细胞外和细胞内靶点提供有价值的新见解，用于内皮素产生和血管张力的药理学甚至治疗调节。