Mode of cleavage of porcine big endothelin-1 by aspartic proteinases.
Cleavage sites of porcine big endothelin-1 (big ET-1, 1-39) by cathepsin D were examined and compared with those by other aspartic proteinases including pepsin. Cathepsin D cleaved not only the Trp21-Val22 bond, but also the Asp18-Ile19 bond of big ET-1[1-39]. The mature ET-1[1-21], generated by the cleavage between Trp21 and Val22, was subsequently degraded by removal of the C-terminal tripeptide (Ile19-Ile20-Trp21). On the other hand, pepsin cleaved the Trp21-Val22 bond of big ET-1[1-39] to produce ET-1[1-21], but did not degrade the generated ET-1[1-21]. These results indicate that aspartic proteinases such as cathepsin D and pepsin are capable of converting big ET-1[1-39] to ET-1[1-21], whereas the former proteinase is by no means specific for the Trp21-Val22 bond of big ET-1[1-39].
Takaoka
M
M
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Hukumori
Y
Y
Shiragami
K
K
Ikegawa
R
R
Matsumura
Y
Y
Morimoto
S
S
D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002402:Cathepsin D / Q000378:metabolism; D019332:Endothelin-1; D016232:Endothelins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D010434:Pepsin A / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D013552:Swine
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D016282:Aspartic Acid Endopeptidases; D010434:Pepsin A; D002402:Cathepsin D