Met-ase: Cloning and distinct chromosomal location of a serine protease preferentially expressed in human natural killer cells
- Austin Research Institute, Austin Hospital, Victoria (Australia)
- NCI-Frederick Cancer Research and Development Center, Frederick, MD (United States)
- Georgia Institute of Technology, Atlanta, GA (United States)
A cDNA clone encoding a human NK serine protease was obtained by screening a [lambda]-gt10 library from the Lopez NK leukemia with the rat natural killer Met-ase (RNK-Met-1) cDNA clone. In Northern blot analysis human Met-ase (Hu-Met-1) cDNA hybridized with a 0.9-kb mRNA in two human NK leukemia cell lines, unstimulated human PBMC, and untreated purified CD3[sup [minus]]CD56[sup +] large granular lymphocytes. Unlike other members of the granzyme family that are highly expressed in activated peripheral T cells, the Hu-Met-1 transcript was barely detected in a population of PMA and ionomycin or IL-2-treated high density T cells. Several in vitro cultured Burkitt lymphomas, chronic- and promyeloid leukemias, acute lymphoblastic leukemias, and colon and ovarian carcinomas did not express Hu-Met-1 mRNA. Hu-Met-1 mRNA expression in a small number of human T cell tumor lines did not correlate with any particular phenotype or stage of development. The presence of Hu-Met-1 mRNA closely correlated with the Met-ase activity of cellular lysates prepared from these various human peripheral blood subsets and in vitro cultured cell lines. Met-ase activity detected in whole cell lysates of cytotoxic lymphocytes was associated with the cytoplasmic granules of these cells. The nucleotide sequence of the Hu-Met-1 cDNA clone encodes a predicted serine protease of 257 amino acids. The predicted protein is an active enzyme of 232 amino acids with a calculated unglycosylated m.w. of 27,100. Hu-Met-1 is 66% identical to RNK-Met-1 at the amino acid level. The human and rat mature protein sequences conserve the active site His, Asp, and Ser amino acids that form the catalytic triad of serine proteases, all 8 cysteine residues, and several amino acids critical in the formation of the substrate binding pocket. The gene for the Hu-Met-1 serine protease is located on chromosome 19, which distinguishes it from any other member of the human granzyme family. 46 refs., 5 figs., 2 tabs.
- OSTI ID:
- 7309258
- Journal Information:
- Journal of Immunology; (United States), Journal Name: Journal of Immunology; (United States) Vol. 151:11; ISSN 0022-1767; ISSN JOIMA3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHROMOSOMES
CLONING
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
ENZYMES
GENE REGULATION
GENES
GENETIC MAPPING
HUMAN CHROMOSOME 19
HUMAN CHROMOSOMES
HYBRIDIZATION
HYDROLASES
LEUKOCYTES
MAPPING
MATERIALS
NATURAL KILLER CELLS
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PROTEINS
SERINE PROTEINASES
STRUCTURAL CHEMICAL ANALYSIS