Wilharm E, Tschopp J, Jenne D E
Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Am Klopferspitz 18A, D-82152, Martinsried, Germany.
FEBS Lett. 1999 Oct 1;459(1):139-42. doi: 10.1016/s0014-5793(99)01200-4.
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.
T细胞和自然杀伤（NK）细胞的类胰蛋白酶活性有助于诱导靶细胞凋亡，但在小鼠T细胞中，只有颗粒酶A（GzmA）被证明具有Z-赖氨酸-苄酯酶活性。GzmA缺陷小鼠表现出残余的Z-赖氨酸-苄酯水解活性和几乎正常水平的淋巴细胞介导的细胞毒性。在此，我们报告重组小鼠颗粒酶K（GzmK）的克隆及生化特性。纯化的小鼠蛋白显示出Z-赖氨酸-苄酯水解活性，并且像人同源物一样，被α-胰蛋白酶抑制剂轻链比库宁所抑制。我们得出结论，GzmA缺陷T细胞表达的GzmK导致了剩余的Z-赖氨酸-苄酯活性。GzmA和GzmK之间的功能相似性可能解释了在GzmA缺陷小鼠中观察到的细微免疫缺陷。
