The gene encoding a human natural killer cell granule serine protease,Met-ase 1, maps to chromosome 19p13.3
✍ Scribed by Elizabeth Baker; Grant R. Sutherland; Mark J. Smyth
- Publisher
- Springer-Verlag
- Year
- 1994
- Tongue
- English
- Weight
- 184 KB
- Volume
- 39
- Category
- Article
- ISSN
- 0093-7711
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✦ Synopsis
Cytotoxic lymphocytes play a pivotal role in immune responses against tumors, viruses, and transplanted tissue . Lymphocyte-mediated cytolysis by both cytotoxic T lymphocytes (CTL) and natural killer (NK) cells is generally associated with the formation of membrane lesions on target cells, caused by exocytosis of cytoplasmic granule serine proteases (granzymes; Tschopp and Jongeneel 1988) and a poreforming protein, perforin . Granzymes represent about 90% of the total granule proteins of CTL and NK cells. Little is known, however, about their gene regulation and biological function. A putative role for granzymes in cytolysis has not been universally accepted despite the fact that DNA fragmenting properties have been postulated for two members of this granzyme family when combined with perforin (Shi et al. 1992a; Shi et al. 1992b). Until recently, granzymes cloned in humans, mouse, and rat encoded just three granzyme activities (tryptase, Asp-ase, and chymase) and all were expressed exclusively in T cells, their thymic precursors, and NK cells . We recently purified a novel 30 000 Mr granzyme that cleaves after methionine residues (a Met-ase; designated RNK-Met-1) from the cytotoxic granules of the rat NK cell leukemia, RNK-16 (Smyth et al. 1992). Isolation and sequencing of the cDNA encoding RNK-Met-l, and subsequently a human cDNA equivalent, human Met-ase 1 (Hu-Met-1), revealed these genes to encode unique granzymes (less than 45% identical to any other granzyme) with a restricted expression in CD3-NK cells ). Furthermore, our previous studies using somatic cell hybrids mapped the Hu-Met-1 gene locus to chromosome 19 ).