title: Interaction between protein kinase C and regulatory ligand is enhanced by a chelatable pool of cellular zinc.
abstract: At micromolar concentrations, zinc (Zn) and cadmium, but not other metals, greatly augmented binding of [3H]phorbol dibutyrate ([3H]PDBu) to protein kinase C (PKC) in cell homogenates and intact cells (in the presence of ionophore). Increased binding persisted for several hours. The heavy-metal chelating agent 1,10-phenanthroline completely reversed the increased [3H]PDBu binding in cells pretreated with 65Zn and ionophore and this was associated with a decline of about 20% in cell-associated 65Zn, suggesting that a relatively small pool of intracellular Zn acts on PKC. This may be a membrane-associated pool, since 65Zn readily bound to isolated erythrocyte inside-out membranes. Phenanthroline also partially inhibited binding of [3H]PDBu to PKC in untreated cells and extracts in a Zn-reversible manner. Therefore, cellular Zn appears to regulate the interaction of ligand with PKC. PKC bound to a Zn affinity column and was eluted by metal-chelator, confirming that Zn interacts directly with PKC.
authors.affiliation: Department of Medicine, University of Adelaide, Queen Elizabeth Hospital, Woodville, Australia.
authors.forename: I J
authors.initials: IJ
authors.lastname: Forbes
authors.forename: P D
authors.initials: PD
authors.lastname: Zalewski
authors.forename: C
authors.initials: C
authors.lastname: Giannakis
authors.forename: H S
authors.initials: HS
authors.lastname: Petkoff
authors.forename: P A
authors.initials: PA
authors.lastname: Cowled
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D002712:Chlorides / Q000494:pharmacology*; D002846:Chromatography, Affinity; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008024:Ligands; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology*; D017967:Zinc Compounds
chemical_list: D002712:Chlorides; D008024:Ligands; D017967:Zinc Compounds; D015240:Phorbol 12,13-Dibutyrate; C016837:zinc chloride; D011493:Protein Kinase C; D015032:Zinc