The natural killer cell serine protease geneLmet1maps to mouse chromosome 10

✍ Scribed by Kevin Y. T. Thia; Nancy A. Jenkins; Debra J. Gilbert; Neal G. Copeland; Mark J. Smyth

• Publisher: Springer-Verlag
• Year: 1995
• Tongue: English
• Weight: 356 KB
• Volume: 41
• Category: Article
• ISSN: 0093-7711
• DOI: 10.1007/bf00188433

✦ Synopsis

Cytotoxic lymphocytes play a key role in immune responses against viruses and tumors (Trinchieri 1989). Lymphocytemediated cytolysis by both cytotoxic T lymphocytes (CTL) and natural killer (NK) cells is often 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 pore-forming protein, perforin (Young 1989). A variety of granzymes have been found to reside within the cytoplasmic granules of cytotoxic lymphocytes (Jenne and Tschopp 1988), but unlike perforin, isolated serine proteases are not intrinsically lytic. However, a role for serine proteases in cellular cytotoxicity has been supported by the ability of protease inhibitors to completely abrogate lymphocyte cytotoxicity (Hudig et al. 1991), and the demonstration that serine proteases can initiate DNA fragmentation in target cells transfected (Shiver et al. 1992) or pretreated with a sublytic concentration of perforin (Shi et al. 1992 a, Shi et al. 1992 b). Granzymes cloned in human, mouse, and rat encode four granzyme activities (tryptase, Asp-ase, chymase, and Metase) and all are expressed in either T cells, their thymic precursors, and/or NK cells (Jenne and Tschopp 1988;Tschopp and Nabholz 1990;Garcia-Sanz et al. 1990). In particular, a rat granzyme that cleaves after methionine residues (a Met-ase), but not phenylalanine residues (a chymase), (designated RNK-Met-1; Smyth et al. 1992) and its human equivalent, human Met-ase 1 (designated Hu-Met-1), are unique granzymes (less than 45% identical to any other granzymes) with restricted expression in CD3-NK cells (Smyth et al. 1992;Smyth et al. 1993).

Previous gene mapping studies have divided the cytotoxic lymphocyte class of serine proteases into three chromosomal groups: 1) HFSP (Fink et al. 1993) and