THE CALPAIN CASCADE - MU-CALPAIN ACTIVATES M-CALPAIN

m-Calpain, which usually requires near-millimolar Ca2+ for activation, undergoes autolysis at 25 mu M Ca2+ in the presence of mu-calpain, m- Calpain in itself exhibits no sign of autolysis around this Ca2+ conce ntration. Half-maximal rate of the reaction occurs at 30 mu M Ca2+, sh owing that it is mu-calpain that catalyzes the limited proteolysis of m-calpain in an intermolecular reaction (''heterolysis''). This hetero lytic step is accompanied by the activation of m-calpain: mu- and m-ca lpain preincubated together at 25 mu M Ca2+ show significantly higher activity than the sum of activities of mu- and m-calpains preincubated separately, m-Calpain is sensitized to Ca2+ by mu-calpain-mediated ac tivation: the half-maximal value of 160 mu M for activation is lowered to 64 mu M, which is similar to the shift found in m-calpain autoacti vation. We suggest that these in vitro observations are relevant in vi vo and the calpain cascade may play an important role in coordinating the functioning of calpains in living cells.