title: Synergy between zinc and phorbol ester in translocation of protein kinase C to cytoskeleton.
abstract: Protein kinase C was measured in the cytoskeletal fraction of lymphocytes, platelets and HL60 cells, by specific binding of [3H]phorbol dibutyrate and by immunoblotting with antibody to a consensus sequence in the regulatory domain of alpha-, beta- and gamma-isozymes of protein kinase C. Treatment of cells for 40 min with a combination of zinc (2-50 microM), zinc ionophore pyrithione and unlabelled phorbol dibutyrate (200 nM) caused up to a ten-fold increase in cytoskeletal protein kinase C and a corresponding decrease in other cellular compartments. Omission of any of the reagents resulted in much less or no translocation. These effects were inhibited by 1,10-phenanthroline, which chelates zinc, and were not seen with calcium. Increase in cytoskeletal protein kinase C persisted for several hours and appeared to involve attachment of the enzyme to actin microfilaments. We propose that zinc, like calcium, regulates the distribution of PKC in cells. However, unlike calcium which controls the binding of PKC to the lipid component on cell membranes, zinc controls the distribution of PKC to membrane cytoskeleton, possibly actin.
authors.affiliation: Department of Medicine, University of Adelaide, Australia.
authors.forename: P D
authors.initials: PD
authors.lastname: Zalewski
authors.forename: I J
authors.initials: IJ
authors.lastname: Forbes
authors.forename: C
authors.initials: C
authors.lastname: Giannakis
authors.forename: P A
authors.initials: PA
authors.lastname: Cowled
authors.forename: W H
authors.initials: WH
authors.lastname: Betts
mesh_terms: D001792:Blood Platelets / Q000201:enzymology*; D002460:Cell Line; D002712:Chlorides / Q000494:pharmacology*; D003599:Cytoskeleton / Q000201:enzymology*; D004357:Drug Synergism; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000201:enzymology*; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011493:Protein Kinase C / Q000097:blood / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology*; D017967:Zinc Compounds
chemical_list: D002712:Chlorides; D017967:Zinc Compounds; D015240:Phorbol 12,13-Dibutyrate; C016837:zinc chloride; D011493:Protein Kinase C; D015032:Zinc