Interaction of human calpains I and II with high molecular weight and low molecular weight kininogens and their heavy chain: mechanism of interaction and the role of divalent cations.
Calpain I prepared from human erythrocytes was half-maximally and maximally activated at 23 and 35 microM calcium ion, and two preparations of calpain II from human liver and kidney were half-maximally activated at 340 and 220 microM calcium ion and maximally activated at 900 microM calcium ion, respectively. High molecular weight (HMW) and low molecular weight (LMW) kininogens isolated from human plasma and the heavy chain prepared from these proteins inhibited calpain I as well as calpain II. The molar ratios of calpains to HMW kininogen to give complete inhibition of calpains were 1.4 for calpain I and 2.0 for calpain II, and those of calpains to heavy chain were 0.40-0.66 for calpain I and 0.85 for calpain II. LMW kininogen did not completely inhibit the calpains even with an excess amount of kininogen. The apparent binding ratio of calpain to HMW kininogen estimated from the disc gel electrophoretic analysis, however, was found to be 2:1, whereas those of calpain to LMW kininogen and of calpain to heavy chain were found to be 1:1. Calpains and kininogens failed to form complexes in the absence of calcium ion. In the presence of calcium ion, however, they formed the complexes, which were dissociable by the addition of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. The minimum concentrations of calcium ion required to induce complex formation between calpain I and kininogens and calpain II and kininogens were 70 and 100 microM, respectively. Some other divalent cations such as Mn2+, Sr2+, and Ba2+ were also able to induce the complex formation between calpains and kininogens.(ABSTRACT TRUNCATED AT 250 WORDS)
D002118:Calcium / Q000494:pharmacology; D002154:Calpain / Q000378:metabolism*; D002413:Cations, Divalent; D006801:Humans; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D007704:Kininogens / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D046911:Macromolecular Substances; D008970:Molecular Weight
D002413:Cations, Divalent; D007704:Kininogens; D046911:Macromolecular Substances; D002154:Calpain; D002118:Calcium