Biological activities of granzyme K are conserved in the mouse and account for residual Z-Lys-SBzl activity in granzyme A-deficient mice.
Tryptase-like activities of T and NK cells contribute to the induction of target cell apoptosis, but only granzyme A (GzmA) has been shown to exhibit Z-Lys-SBzl esterase activity in murine T cells. GzmA-deficient mice exhibit residual Z-Lys-SBzl hydrolyzing activity and almost normal levels of lymphocyte-mediated cytotoxicity. Here we report the cloning and biochemical characterization of recombinant mouse granzyme K (GzmK). The purified murine protein shows Z-Lys-SBzl hydrolyzing activity and is inhibited by bikunin, the light chain of inter-alpha-trypsin inhibitor, like the human homolog. We conclude that GzmK expressed by GzmA-deficient T cells accounts for the remaining Z-Lys-SBzl activity. Functional similarities between GzmA and GzmK may explain the subtle immunological deficits observed in GzmA-deficient mice.
Wilharm
E
E
Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Am Klopferspitz 18A, D-82152, Martinsried, Germany.
Tschopp
J
J
Jenne
D E
DE
D000818:Animals; D053818:Chymases; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D004926:Escherichia coli; D006023:Glycoproteins / Q000378:metabolism; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008562:Membrane Glycoproteins; D051379:Mice; D008958:Models, Molecular; D011994:Recombinant Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism; D013379:Substrate Specificity; D014360:Trypsin Inhibitor, Kunitz Soybean; D053802:Tryptases
D018076:DNA, Complementary; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C109148:SPINT2 protein, human; D015842:Serine Proteinase Inhibitors; C509190:Tpsb2 protein, mouse; D014360:Trypsin Inhibitor, Kunitz Soybean; D053804:Granzymes; C000602229:GzmK protein, mouse; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; C509222:Tpsab1 protein, mouse; D053802:Tryptases; C509212:GZMA protein, human; D008239:Lysine