title: Different susceptibility of human tissue prokallikrein to cleavage by neutrophil proteinases.
abstract: The recent discovery of tissue prokallikrein (TproK) on the cell surface of human neutrophils prompted this study to test the sensitivity of the kallikrein precursor to proteolysis by neutrophil-derived elastase and cathepsin G. Purified recombinant human TproK was readily degraded by cathepsin G via distinct cleavage sites into two major fragments of 5 and 8 kDa which are devoid of enzymatic activity. Leukocyte elastase caused a rapid conversion of TproK into [des-Ile1]-TK, a differentially processed tissue kallikrein (TK) isoform with truncated N-terminus that appeared to be resistant to further cleavage by elastase. Kinetic data demonstrated the cleavage of amidolytic kallikrein substrates and the release of kinin from HMW kininogen, but the single amino acid deletion results in a severe reduction of catalytic activity for [des-Ile1]-TK compared to the mature enzyme. These in vitro observations support the possibility that the inter-relationships among TproK and neutrophil proteinases may provide a sensitive regulatory system to balance the kallikrein-kinin cascade during inflammatory events.
authors.affiliation: Institute for Biochemistry, Darmstadt University of Technology, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Podlich
authors.forename: M
authors.initials: M
authors.lastname: Kemme
mesh_terms: D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007610:Kallikreins / Q000378:metabolism*; D019272:Leukocyte Elastase / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*; D011499:Protein Processing, Post-Translational; D012697:Serine Endopeptidases
chemical_list: D004792:Enzyme Precursors; D002403:Cathepsins; D007610:Kallikreins; D012697:Serine Endopeptidases; C052910:prokallikrein, tissue; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase