Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 413-422 |
| Number of pages | 10 |
| Journal | Molecular Immunology |
| Volume | 36 |
| Issue number | 7 |
| DOIs | |
| State | Published - May 1999 |
Funding
The authors thank Carol Clayberger and Elizabeth Mellins for helpful review of the manuscript. Alan M. Krensky is the Shelagh Galligan Professor of Pediatrics and a Burroughs Wellcome Scholar in Experimental Therapeutics. Dennis A. Hanson was the recipient of a Graduate Research Fellowship from the National Science Foundation. This work was supported by NIH grants R01 DK35008 and AI43348.
Keywords
- Biochemistry
- CTL
- Cytolytic granules
- NK cells
ASJC Scopus subject areas
- Molecular Biology
- Immunology