vanderSpek J C, Sutherland J, Sampson E, Murphy J R
Evans Department of Clinical Research, Boston University Medical Center Hospital, MA 02118, USA.
Protein Eng. 1995 Dec;8(12):1317-21. doi: 10.1093/protein/8.12.1317.
A gene fusion encoding DAB389 sIL-15 was constructed in which the catalytic and transmembrane domains of native diphtheria toxin (DAB389) are genetically linked to the N-terminus of simian interleukin 15 (sIL-15). It was demonstrated that the cytotoxic action of DAB389 sIL-15 is mediated through the IL-15 receptor. Since toxicity may be blocked with chloroquine, it was concluded that following binding to the IL-15 receptor, the fusion toxin is internalized by receptor-mediated endocytosis and must pass through an acidic compartment in order to facilitate the delivery of the catalytic domain to the cytosol of target cells. As a non-toxic control, the ADP-ribosyltransferase defective mutant DA(E149S)B389 sIL-15 was constructed. It was demonstrated that both sIL-15 and DA(E149S)B389 sIL-15 stimulate protein and DNA synthesis in IL-15 receptor-positive CTLL-2 cells in vitro.
