Processing, subcellular localization, and function of 519 (granulysin), a human late T cell activation molecule with homology to small, lytic, granule proteins.
CTL and NK cells share a common cytolytic mechanism that involves regulated exocytosis of lytic molecules stored within cytoplasmic granules. Here we describe the processing, subcellular localization, and function of a T and NK cell-specific granule protein that shares homology with small, lytic granule-associated molecules. The gene coding for this protein, 519, is expressed late after T cell activation. Antisera raised against a 519/glutathione-S-transferase fusion protein and a series of peptides derived from the 519 protein sequence permitted the identification of two small CTL protein products of 15 and 9 kDa that are exocytosed after stimulation through the TCR. The 9-kDa product is a processed form of 519 and differs from the 15-kDa product in both its amino and carboxyl terminus. While both 519 proteins are found in cytoplasmic granules, the 9-kDa form is also present in dense, highly cytolytic granules. Functional studies indicate that this protein is lytic against tumor cell targets. The cell type- and stage-specific expression pattern of 519 along with its subcellular localization are reminiscent of molecules that play a vital role in granule-mediated cytolysis by CTL and NK cells. Its lytic activity suggests the involvement of 519 in CTL effector function.
Peña
S V
SV
Department of Pediatrics, Stanford University School of Medicine, CA 94305, USA.
Hanson
D A
DA
Carr
B A
BA
Goralski
T J
TJ
Krensky
A M
AM
D000595:Amino Acid Sequence; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D005089:Exocytosis / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; C075005:GNLY protein, human; D011948:Receptors, Antigen, T-Cell