Synergy between zinc and phorbol ester in translocation of protein kinase C to cytoskeleton

• Published in: FEBS letters Vol. 273; no. 1-2; pp. 131 - 134
• Main Authors: Zalewski, P.D., Forbes, I.J., Giannakis, C., Cowled, P.A., Betts, W.H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 29.10.1990; Elsevier
• Subjects: 1,10-phenanthroline; Biological and medical sciences; Blood Platelets - enzymology; calcium; Cell Line; Cell physiology; Chlorides - pharmacology; Cytoskeleton; Cytoskeleton - enzymology; Drug Synergism; Fundamental and applied biological sciences. Psychology; Humans; Kinetics; Lymphocytes - enzymology; Molecular and cellular biology; Nonidet P-40; NP40; PDBu; Phe; phenylmethylsulphonyl fluoride; Phorbol 12,13-Dibutyrate - metabolism; Phorbol 12,13-Dibutyrate - pharmacology; phorbol dibutyrate; Phorbol ester; PKC; PMSF; Protein Binding; Protein kinase C; Protein Kinase C - blood; Protein Kinase C - metabolism; zinc; Zinc - pharmacology; Zinc Compounds; Zinc ionophore; Protein kinase C; PDBu; Zn; PMSF; Zinc ionophore; Phorbol ester; Cytoskeleton; PKC; NP40; Phe; Ca; Human; Ionic channel; Enzyme; Zinc
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(90)81067-X

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 α-, β- and γ-isozymes of protein kinase C. Treatment of cells for 40 min with a combination of zinc (2–50 μM), 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.