Interaction of angiotensin-converting enzyme (ACE) with membrane-bound carboxypeptidase M (CPM) - a new function of ACE.
Angiotensin-converting enzyme (ACE) demonstrates, besides its typical dipeptidyl-carboxypeptidase activity, several unusual functions. Here, we demonstrate with molecular, biochemical, and cellular techniques that the somatic wild-type murine ACE (mACE), stably transfected in Chinese Hamster Ovary (CHO) or Madin-Darby Canine Kidney (MDCK) cells, interacts with endogenous membranal co-localized carboxypeptidase M (CPM). CPM belongs to the group of glycosylphosphatidylinositol (GPI)-anchored proteins. Here we report that ACE, completely independent of its known dipeptidase activities, has GPI-targeted properties. Our results indicate that the spatial proximity between mACE and the endogenous CPM enables an ACE-evoked release of CPM. These results are discussed with respect to the recently proposed GPI-ase activity and function of sperm-bound ACE.
Leibniz-Institut für Molekulare Pharmakologie, D-13125 Berlin, Germany and Charité-Universitätsmedizin Berlin, D-10117 Berlin, Germany.
Xiaoou
X
Sun
Burkhard
B
Wiesner
Dorothea
D
Lorenz
Gisela
G
Papsdorf
Kristin
K
Pankow
Po
P
Wang
Nils
N
Dietrich
Wolf-Eberhard
WE
Siems
Björn
B
Maul
D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D003432:Cross-Linking Reagents; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols / Q000737:chemistry; D007150:Immunohistochemistry; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013094:Spermatozoa / Q000201:enzymology / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D003432:Cross-Linking Reagents; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D010738:Type C Phospholipases; D007703:Peptidyl-Dipeptidase A; C058479:carboxypeptidase M; D008666:Metalloendopeptidases