Cytotoxic lymphocytes are characterized by their inclusion of cytoplasmic granules that fuse with the plasma membrane following target cell recognition. We previously identified a cytotoxic granule membrane protein designated p15-TIA-1 that is immunochemically related to an RNA-recognition motif (RRM)-type RNA-binding protein designated p40-TIA-1, Although it was suggested that p15-TIA-1 might be derived from p40-TIA-1 by proteolysis, N-terminal amino acid sequencing of p15-TIA-1 immunoaffinity purified from a natural killer (NK) cell line by using monoclonal antibody (mAb) 2G9 revealed that p15-TIA-1 is identical to the deduced amino acid sequence of NKG7 and GIG-1, cDNAs isolated from NK cells and granulocyte-colony-stimulating factor-treated mononuclear cells, respectively, Epitope mapping revealed that mAb 2G9 recognizes the C terminus of p15-TIA-1 and p40-TIA-1, The deduced amino acid sequence of p15-TIA-1/NKG7/GIG-1 predicts that the protein possesses four transmembrane domains, and immune-electron microscopy localizes the endogenous protein to the membranes of cytotoxic granules in NK cells, Given its subcellular localization, we propose to rename this protein GMP-17, for granule membrane protein of 17 kDa, Immunofluorescence microscopy of freshly isolated NK cells confirms this granular localization, Target cell-induced NK cell degranulation results in translocation of GMP-17 from granules to the plasma membrane, suggesting a possible role for GMP-17 in regulating the effector function of lymphocytes and neutrophils.
