Calmodulin interacts with angiotensin‐converting enzyme‐2 (ACE2) and inhibits shedding of its ectodomain

Angiotensin‐converting enzyme‐2 (ACE2) is a regulatory protein of the renin–angiotensin system (RAS) and a receptor for the causative agent of severe‐acute respiratory syndrome (SARS), the SARS‐coronavirus. We have previously shown that ACE2 can be shed from the cell surface in response to phorbol esters by a process involving TNF‐α converting enzyme (TACE; ADAM17). In this study, we demonstrate that inhibitors of calmodulin also stimulate shedding of the ACE2 ectodomain, a process at least partially mediated by a metalloproteinase. We also show that calmodulin associates with ACE2 and that this interaction is decreased by calmodulin inhibitors.