Insulin proteinase liberates from glucagon a fragment known to have enhanced activity against Ca2+ + Mg2+-dependent ATPase.
We find, contrary to previous reports, that substantial cleavage of glucagon by insulin proteinase occurs at only one region, namely the double-basic sequence -Arg17-Arg18-. Cleavage takes place almost exclusively between these two residues, liberating fragments glucagon-(1-17) and glucagon-(18-29). Others have shown that the fragment glucagon-(19-29) is 1000-fold more efficient compared with intact glucagon, at inhibiting the Ca2+-activated and Mg2+-dependent ATPase activity and the Ca2+ pump of liver plasma membranes. We show that this fragment is not liberated in detectable quantities by our insulin proteinase preparation. On the other hand, others have shown that glucagon-(18-29), though less active than glucagon-(19-29), was still 100-fold more active than glucagon itself in the above-mentioned system. Our observations represent the first demonstration of the release by insulin proteinase of a hormone fragment having enhanced activity, although it has yet to be shown that the activity of this fragment is important in vivo. Since the formation of glucagon-(19-29) from glucagon-(18-29) would involve merely removal of Arg18, a second enzyme might exist to provide the more active fragment.
Rose
K
K
Département de Biochimie Médicale, Centre Médical Universitaire, Geneva, Switzerland.
Savoy
L A
LA
Muir
A V
AV
Davies
J G
JG
Offord
R E
RE
Turcatti
G
G
D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid; D005934:Glucagon / Q000378:metabolism*; D007339:Insulysin / Q000378:metabolism*; D013058:Mass Spectrometry; D010446:Peptide Fragments / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*
D010446:Peptide Fragments; D005934:Glucagon; D010447:Peptide Hydrolases; D007339:Insulysin; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases