Alternative splicing of the mRNA coding for the human endothelial angiotensin-converting enzyme: a new mechanism for solubilization.
Angiotensin converting enzyme (ACE) is a zinc metalloprotease anchored in the plasma membrane with a carboxy-terminal hydrophobic domain. In addition, the existence of a soluble form of ACE lacking the transmembrane domain has been reported. We show evidence for the existence of an mRNA specific for this isoform produced by alternative splicing. In human umbilical vein endothelial cells, two ACE mRNAs of different length (4.3 and 3.5 kb) were detected by Northern blot. Ribonuclease protection assays and the sequence of a PCR-amplified cDNA fragment show that the shortened ACE mRNA lacks the exons coding for the transmembrane domain of the protein. As this mRNA could be the source of soluble ACE, plasma ACE activity may be regulated on the level of mRNA processing.
Sugimura
K
K
Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, Berlin-Buch, D-13122, Germany. sugimura@mdc.berlin.de
Tian
X L
XL
Hoffmann
S
S
Ganten
D
D
Bader
M
M
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D019105:Random Amplified Polymorphic DNA Technique; D012995:Solubility
D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A