NK lytic-associated molecule: a novel gene selectively expressed in cells with cytolytic function.
NK cells are most effective in killing a broad spectrum of primary tumor cells after stimulation with cytokines. We have cloned a novel gene, designated NKLAM (for NK lytic-associated molecule), whose expression is associated with this cytokine-enhanced process. NKLAM expression is up-regulated in NK cells by IL-2 and IFN-beta. NKLAM is also selectively expressed by activated macrophages and CTL. Treatment of NK cells and CTL with NKLAM antisense oligonucleotides specifically decreases their cytolytic activity, while having no effect on cell growth. The NKLAM gene encodes a 62-kDa ring finger-containing protein that localizes to the cytoplasmic granules in NK cells. Further study of this gene may add to our understanding of cytotoxic processes common to NK cells, CTL, and activated macrophages.
Kozlowski
M
M
Department of Pathology, St. Louis University School of Medicine, Veterans Administration Medical Center, MO 63106, USA.
Schorey
J
J
Portis
T
T
Grigoriev
V
V
Kornbluth
J
J
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002999:Clone Cells; D003594:Cytoplasmic Granules / Q000201:enzymology / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D005786:Gene Expression Regulation / Q000276:immunology*; D053804:Granzymes; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers / Q000235:genetics / Q000276:immunology
D008565:Membrane Proteins; C120864:NK lytic-associated molecule; D016899:Interferon-beta; C509213:GZMB protein, human; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases