The protein inhibitor of calcium-dependent proteases: purification from bovine heart and possible mechanisms of regulation.
A bovine heart protein which specifically inhibits calcium-dependent proteases has been purified to near homogeneity. The purified inhibitor had a Stokes radius of 6.8 nm estimated by gel filtration and a molecular weight of 145,000 estimated by sodium dodecyl sulfate-gel electrophoresis. There is evidence that it may be a glycoprotein. The inhibitor could be phosphorylated by bovine heart cyclic AMP-dependent protein kinase, and its inhibitory effect on Peak II (high-calcium-requiring) protease was modestly increased. However, no other phosphorylating or dephosphorylating conditions significantly influenced its activity. The inhibitor was not hydrolyzed by calcium-dependent proteases, but it was very sensitive to proteolytic inactivation by trypsin or proteases present in a lysosomal fraction from rat heart. Thus, proteolysis may represent a mechanism for decreasing the activity of the inhibitor in different physiologic or pathologic conditions.
D000818:Animals; D002154:Calpain; D002417:Cattle; D000242:Cyclic AMP / Q000494:pharmacology; D010450:Endopeptidases / Q000302:isolation & purification* / Q000378:metabolism; D006023:Glycoproteins / Q000302:isolation & purification* / Q000502:physiology; D007672:Kidney Cortex / Q000201:enzymology; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology; D009132:Muscles / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011817:Rabbits; D051381:Rats
D006023:Glycoproteins; C039304:calpain inhibitors; D000242:Cyclic AMP; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D010450:Endopeptidases; D002154:Calpain