Differential interactions of human kallikrein-binding protein and alpha 1-antitrypsin with human tissue kallikrein.
The characteristics of a new kallikrein-binding protein in human serum and its activities were studied. Both the kallikrein-binding protein and alpha 1-antitrypsin form 92 kDa SDS-stable and heat-stable complexes with human tissue kallikrein. In non-SDS/PAGE, the mobility of these complexes differ. Complex-formation between kallikrein and the binding protein is inhibited by heparin, whereas that between kallikrein and alpha 1-antitrypsin is heparin-resistant. In normal or alpha 1-antitrypsin-deficient-serum, the amount of 92 kDa SDS-stable complex formed upon addition of kallikrein is not related to serum alpha 1-antitrypsin levels. The rate of complex-formation between kallikrein and the binding protein is 12 times higher than that between kallikrein and alpha 1-antitrypsin. Purified alpha 1-antitrypsin, which exhibits normal elastase binding, has a kallikrein-binding activity less than 5% of that of serum. Binding of tissue kallikrein in serum is not inhibited by increasing elastase concentrations, and elastase binding in serum is not inhibited by excess tissue kallikrein. A specific monoclonal antibody to human alpha 1-antitrypsin does not bind to either 92 kDa endogenous or exogenous kallikrein complexes isolated from human serum. The studies demonstrate a new tissue kallikrein-binding protein, distinct from alpha 1-antitrypsin, is present in human serum.
Chen
L M
LM
Department of Pharmacology, Medical University of South Carolina, Charleston 29425.
Chao
L
L
Mayfield
R K
RK
Chao
J
J
D001667:Binding, Competitive; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007610:Kallikreins / Q000378:metabolism*; D007700:Kinetics; D008970:Molecular Weight; D010196:Pancreatic Elastase / Q000378:metabolism; D015843:Serpins; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D002352:Carrier Proteins; D015843:Serpins; D000515:alpha 1-Antitrypsin; C051324:kallistatin; D006493:Heparin; D007610:Kallikreins; D010196:Pancreatic Elastase