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 kinases that are central to many signal transduction pathways. Among the PKC isozymes, only PKC epsilon has been reported to exhibit full oncogenic potential. PKC epsilon also displays unique substrate specificity and intracellular localization. To examine the interrelationship between 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 localize with the Golgi network and other compartments, whereas the zinc-finger domain localized exclusively at the Golgi. Golgi-specific glycosaminoglycan sulfation was strongly inhibited in cells overexpressing either holo-PKC epsilon or its zinc-finger domain, while the secretion of sulfated glycosaminoglycans into the medium was impaired in cells expressing the PKC epsilon zinc-finger domain. Thus, these results suggest that PKC epsilon may be involved in specifically regulating Golgi-related processes. Further, the results indicate that PKC epsilon domains other than the kinase domain may also have biological activity and that the zinc-finger domain may function as a subcellular localization signal.
Lehel
C
C
Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Olah
Z
Z
Jakab
G
G
Anderson
W B
WB
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002451:Cell Compartmentation; D017931:DNA Primers / Q000737:chemistry; D006025:Glycosaminoglycans / Q000378:metabolism; D006056:Golgi Apparatus / Q000201:enzymology* / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051744:Protein Kinase C-epsilon; D011994:Recombinant Proteins; D013431:Sulfates / Q000378:metabolism; D014162:Transfection; D016335:Zinc Fingers
D017931:DNA Primers; D006025:Glycosaminoglycans; D007527:Isoenzymes; D011994:Recombinant Proteins; D013431:Sulfates; D015240:Phorbol 12,13-Dibutyrate; C497256:Prkce protein, mouse; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon