PMID- 10449094 OWN - NLM STAT- MEDLINE DCOM- 19990823 LR - 20190826 IS - 0161-5890 (Print) IS - 0161-5890 (Linking) VI - 36 IP - 7 DP - 1999 May TI - Biosynthesis of granulysin, a novel cytolytic molecule. PG - 413-22 AB - Granulysin is a newly described lytic molecule expressed by CTL and NK cells. Three mRNA (519, 520, and 522) and two protein products of 15 and 9 kDa are encoded by the granulysin gene. Stable transfectants overexpressing the predominate 520 mRNA were generated to determine the protein products originating from the translation of this message. A transfectant of the NK cell tumor YT overexpressed both 15 and 9 kDa proteins while a transfectant of the T cell tumor HuT78 produced mainly 15 kDa granulysin. Thus the 520 mRNA is sufficient for production of both 15 and 9 kDa granulysin. 9 kDa granulysin accumulated via post-translational processing of 15 kDa protein and was present intracellularly but not in the cell culture supernatant, indicating specific retention of the 9 kDa protein. An inhibitor of granule acidification, concanamycin A, blocked the processing of 15 kDa granulysin to the 9 kDa form. A deduced structural difference between the two forms of the protein and a decrease in lytic activity of 9 kDa granulysin at granule pH suggest two mechanisms by which a granulysin expressing cell is protected from autolysis during the biosynthesis of this potentially harmful molecule. FAU - Hanson, D A AU - Hanson DA AD - Department of Pediatrics, Stanford University School of Medicine, CA 94305-5208, USA. FAU - Kaspar, A A AU - Kaspar AA FAU - Poulain, F R AU - Poulain FR FAU - Krensky, A M AU - Krensky AM LA - eng GR - AI43348/AI/NIAID NIH HHS/United States GR - R01 DK35008/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Anti-Bacterial Agents) RN - 0 (Antigens, Differentiation, T-Lymphocyte) RN - 0 (Enzyme Inhibitors) RN - 0 (GNLY protein, human) RN - 0 (Macrolides) RN - 80890-47-7 (concanamycin A) SB - IM MH - Anti-Bacterial Agents/pharmacology MH - Antigens, Differentiation, T-Lymphocyte/*biosynthesis/chemistry/immunology/metabolism MH - Dose-Response Relationship, Drug MH - Enzyme Inhibitors MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Hydrogen-Ion Concentration MH - Killer Cells, Natural/*chemistry/immunology MH - Kinetics MH - *Macrolides MH - Precipitin Tests MH - T-Lymphocytes, Cytotoxic/*chemistry/immunology MH - Transfection MH - Tumor Cells, Cultured EDAT- 1999/08/17 00:00 MHDA- 1999/08/17 00:01 CRDT- 1999/08/17 00:00 PHST- 1999/08/17 00:00 [pubmed] PHST- 1999/08/17 00:01 [medline] PHST- 1999/08/17 00:00 [entrez] AID - S0161589099000632 [pii] AID - 10.1016/s0161-5890(99)00063-2 [doi] PST - ppublish SO - Mol Immunol. 1999 May;36(7):413-22. doi: 10.1016/s0161-5890(99)00063-2.