Role for zinc in a cellular response mediated by protein kinase C in human B lymphocytes.
Recent studies have suggested a role for Zn2+, distinct from that of Ca2+, in the subcellular distribution and activation of protein kinase C (PKC). Here we show that Zn2+ is required for a cellular response mediated by PKC, the rapid loss of expression of a human B cell receptor MER, detected by rosetting with mouse erythrocytes. Zn2+, in the presence of the Zn2+ ionophore pyrithione, caused rapid inhibition of MER rosetting at concentrations which induce the translocation and activation of PKC. This required cellular uptake of Zn2+ and was blocked by 1,10-phenanthroline and TPEN which chelate Zn2+ but not Ca2+. Gold, a metal with similar properties, also induced translocation of PKC and inhibition of MER. By contrast, Ca2+ ionophores A23187 and ionomycin, which induce a different pathway of translocation of PKC, had no effect on MER. Phenanthroline and TPEN also blocked the inhibition of MER induced by the PKC activators phorbol ester and sodium fluoride, suggesting that endogenous cellular Zn2+ is required. We propose that some cellular actions of PKC require a Zn(2+)-dependent event and that these may be a target for gold during chrysotherapy in rheumatoid arthritis.
Forbes
I J
IJ
Department of Medicine, University of Adelaide, Queen Elizabeth Hospital, Woodville, South Australia.
Zalewski
P D
PD
Giannakis
C
C
D001310:Auranofin / Q000494:pharmacology; D001402:B-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D010618:Phenanthrolines / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D011971:Receptors, Immunologic / Q000378:metabolism; D012397:Rosette Formation; D015032:Zinc / Q000502:physiology*
D002614:Chelating Agents; D010618:Phenanthrolines; D011971:Receptors, Immunologic; D015240:Phorbol 12,13-Dibutyrate; D001310:Auranofin; D011493:Protein Kinase C; D015032:Zinc; D002118:Calcium