Calcium-dependent neural proteases, widespread occurrence of a species of protease active at lower concentrations of calcium.

A species of neutral protease having high affinity for Ca2+ in the 10(-5) M range, originally found in canine cardiac muscle (Mellgren, R.L. (1980) FEBS Lett. 109, 129-133), is detected in a wide variety of rat tissues when a sensitive assay with 125I-iodinated casein as substrate is employed. This species of protease absolutely requires Ca2+, and other divalent cations are practically inactive. Although the activity of this enzyme apparently shows striking diversity among tissues tested, the enzymes obtained from various sources reveal similar physical and kinetic properties, and are capable of activating as Ca2+-activated, phospholipid-dependent protein kinase by limited proteolysis. The enzyme has a pH optimum at 7.5 to 8.0 and a molecular weight of about 8.8 X 10(4). The enzyme in its purified form is very sensitive to leupeptin and other thiol-protease inhibitors, but that in crude preparations is far less susceptible to the same inhibitors.