PROTEIN-KINASE C-EPSILON IS LOCALIZED TO THE GOLGI VIA ITS ZINC-FINGER DOMAIN AND MODULATES GOLGI FUNCTION

Protein kinase C (PKC) is a multigene family of serine/threonine kinas es that are central to many signal transduction pathways. Among the PK C isozymes, only PKC epsilon has been reported to exhibit full oncogen ic potential. PKC epsilon also displays unique substrate specificity a nd intracellular localization. To examine the interrelationship betwee n the biological effects and domain structure of PKC epsilon, NIH 3T3 cells were stably transfected to overexpress different epitope-tagged fragments of PKC epsilon. The overexpressed proteins each contain the epsilon-tag peptide at the C terminus to allow ready detection with an antibody specific for the tag. The holo-PKC epsilon was found to loca lize with the Golgi network and other compartments, whereas the zinc-f inger domain localized exclusively at the Golgi. Golgi-specific glycos aminoglycan sulfation was strongly inhibited in cells overexpressing e ither holo-PKC epsilon or its zinc-finger domain, while the secretion of sulfated glycosaminoglycans into the medium was impaired in cells e xpressing the PKC epsilon zinc-finger domain. Thus, these results sugg est that PKC epsilon may be involved in specifically regulating Golgi- related processes. Further, the results indicate that PKC epsilon doma ins other than the kinase domain may also have biological activity and that the zinc-finger domain may function as a subcellular localizatio n signal.