Effects of zinc on phospholamban phosphorylation

The effects of zinc can the phosphorylation of phospholamban (PLB) were studied in sarcoplasmic reticulum (SR) membranes prepared from swine ventricular muscle. Zinc produced a dose dependent inhibition of PLB phosphorylation, With the use of phosphorylation site specific antibodies, it was shown that this inhibition was specific for the PLB phosphorylation at a Thr-17. Since phosphorylation of this site is known to be mediated by the Ca2+/calmodulin-dependent protein kinase endogenous to the cardiac SR (SRCaM kinase), the action of zinc on SRCaM kinase was investigated, It was found that (i) zinc inhibited the activity of SRCaM kinase (IC50: 15 mu M) and (ii) zinc concentrations, at the millimolar range, stimulated Ca2+-independent SRCaM kinase autophosphorylation. This ability of zinc to differentiate between autophosphorylation and substrate phosphorylation activities of SRCaM kinase raises the possibility that zinc mediated independent regulation of these processes can occuring the intact heart. (C) 1997 Academic Press.