CHARACTERIZATION OF GMP-17, A GRANULE MEMBRANE-PROTEIN THAT MOVES TO THE PLASMA-MEMBRANE OF NATURAL-KILLER-CELLS FOLLOWING TARGET-CELL RECOGNITION

Cytotoxic lymphocytes are characterized by their inclusion of cytoplas mic granules that fuse with the plasma membrane following target cell recognition. We previously identified a cytotoxic granule membrane pro tein designated p15-TIA-1 that is immunochemically related to an RNA-r ecognition 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 immun oaffinity purified from a natural killer (NK) cell line by using monoc lonal antibody (mAb) 2G9 revealed that p15-TIA-1 is identical to the d educed amino acid sequence of NKG7 and GIG-1, cDNAs isolated from NK c ells and granulocyte-colony-stimulating factor-treated mononuclear cel ls, respectively, Epitope mapping revealed that mAb 2G9 recognizes the C terminus of p15-TIA-1 and p40-TIA-1, The deduced amino acid sequenc e of p15-TIA-1/NKG7/GIG-1 predicts that the protein possesses four tra nsmembrane domains, and immune-electron microscopy localizes the endog enous protein to the membranes of cytotoxic granules in NK cells, Give n its subcellular localization, we propose to rename this protein GMP- 17, for granule membrane protein of 17 kDa, Immunofluorescence microsc opy 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 rol e for GMP-17 in regulating the effector function of lymphocytes and ne utrophils.