Subunit autolysis of mammalian m-calpain upon activation was examined
in kinetic terms using a set of antibodies recognizing different porti
ons of the protease. Activation of m-calpain by calcium resulted in no
apparent autolysis in the large catalytic subunit, whereas the small
regulatory subunit underwent immediate autolysis followed by substrate
proteolysis. This profile of subunit autolysis is distinct from that
of the other ubiquitous isozyme, mu-calpain, in which autolysis of the
large subunit and then of the small subunit precedes substrate proteo
lysis under the normal conditions. The activation state of m-calpain t
hus is not reflected by the large subunit autolysis. The mode and role
of autolysis may vary among calpain isozymes.