Pineal and retinal protein kinase C isoenzymes: cooperative activation by calcium and zinc metallothionein.
Protein kinase C and its family of multiple subspecies play pivotal roles in cell-surface mediated signal transduction. For example, in the process of synthesizing melatonin, the activation of alpha 1-adrenergic receptor sites in the pineal gland causes translocation of protein kinase C, which in turn enhances the beta-adrenergic-activated accumulation of both cyclic AMP and cyclic GMP. In the retina, protein kinase C phosphorylates rhodopsin and hence is involved in visual transduction. The activation of protein kinase C depends on the presence of phospholipid and Ca++. In this communication, we report that the bovine pineal gland and retina possess unique protein kinase C isoenzymes that are distinct from those seen in the rat brain. Furthermore, in retinoblastoma cells in culture, protein kinase C is stimulated by a cooperative interaction between calcium and zinc. Moreover, the subcellular regions of retina that exhibit the highest activity of protein kinase C also possess the highest concentration of zinc. In view of the fact that the bovine pineal gland and retina continually synthesize metallothionein and other low molecular weight zinc binding proteins, we propose that zinc and metallothionein participate in signal transduction in the retina and pineal gland. The action of metallothionein, a zinc binding protein, in activating protein kinase C is opposite to that of calcium binding protein, which is a potent inhibitor of protein kinase C.
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Department of Pharmacology, University of Nebraska College of Medicine, Omaha.
Ebadi
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D000818:Animals; D001921:Brain / Q000201:enzymology; D002118:Calcium / Q000494:pharmacology*; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects; D005134:Eye Neoplasms / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000494:pharmacology*; D010870:Pineal Gland / Q000187:drug effects / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000187:drug effects / Q000201:enzymology*; D012175:Retinoblastoma / Q000201:enzymology; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000201:enzymology; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology
D007527:Isoenzymes; C021267:zinc thionein; D008668:Metallothionein; D011493:Protein Kinase C; D015032:Zinc; D002118:Calcium