Cathepsin L, but not cathepsin B, is a potential kininogenase.
Although papain-like enzymes are strongly inhibited by their natural tight-binding inhibitors of the cystatin superfamily, cathepsins B and L may still retain some residual proteolytic activity toward Z-Phe-Arg-AMC in the presence of an excess of kininogen. This activity is abolished by adding E-64 or chicken cystatin. Cathepsins B and L show a single band of gelatinolytic activity when subjected to gelatin-SDS-PAGE. Adding high Mr kininogen, low Mr kininogen, T-kininogen, or chicken cystatin to cathepsin L results in additional intense bands of enzyme activity corresponding to the protease-inhibitor complexes. Cathepsin B does not produce these additional bands. This gelatinolytic activity was inhibited by E-64, but not by EDTA, PMSF or Pefabloc. Cathepsin L also specifically generated kinins from high and low molecular weight kininogens in vitro, but cathepsin B did not. T-kininogen did not release any immunoreactive kinins when complexed with cathepsin L, as previously observed using tissue kallikreins. The ability of cathepsin L to generate vasoactive peptides raises the question of the physiological significance of this mechanism during inflammation.
Desmazes
C
C
Laboratory of Enzymology and Protein Chemistry, INSERM EMI-U 00-10, University François Rabelais, Faculty of Medicine, Tours, France.
Gauthier
F
F
Lalmanach
G
G
D000818:Animals; D002401:Cathepsin B / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002645:Chickens; D015891:Cystatins / Q000378:metabolism; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000378:metabolism; D019679:Kininogen, High-Molecular-Weight / Q000378:metabolism; D019728:Kininogen, Low-Molecular-Weight / Q000378:metabolism; D007704:Kininogens / Q000378:metabolism; D007705:Kinins / Q000378:metabolism; D011485:Protein Binding
D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D005456:Fluorescent Dyes; D019679:Kininogen, High-Molecular-Weight; D019728:Kininogen, Low-Molecular-Weight; D007704:Kininogens; D007705:Kinins; D002403:Cathepsins; D007610:Kallikreins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L