title: Characterization of GMP-17, a granule membrane protein that moves to the plasma membrane of natural killer cells following target cell recognition.
abstract: 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-T1A-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-T1A-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-T1A-1 and p40-T1A-1. The deduced amino acid sequence of p15-T1A-1/NKG7/GIG-1 predicts that the protein possesses four transmembrane domains, and immuno-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.
authors.affiliation: Division of Tumor Immunology Dana Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Q G
authors.initials: QG
authors.lastname: Medley
authors.forename: N
authors.initials: N
authors.lastname: Kedersha
authors.forename: S
authors.initials: S
authors.lastname: O'Brien
authors.forename: Q
authors.initials: Q
authors.lastname: Tian
authors.forename: S F
authors.initials: SF
authors.lastname: Schlossman
authors.forename: M
authors.initials: M
authors.lastname: Streuli
authors.forename: P
authors.initials: P
authors.lastname: Anderson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D018076:DNA, Complementary / Q000235:genetics; D018604:Epitope Mapping; D005455:Fluorescent Antibody Technique; D007694:Killer Cells, Natural / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D000074019:T-Cell Intracellular Antigen-1; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human