Abstract
REGULATION of pigmentation is of considerable importance throughout the animal kingdom. Photoprotection, social behaviour, and a number of disorders like albinism, vitiligo, and melanoma are affected by the amount and distribution of melanin in the organism. Melanin is synthesised in melanosomes beginning with the oxidation of tyrosine to dihydroxy-phenyalanine (DOPA) by the enzyme tyrosinase. In Cloudman S91 melanoma cells, tyrosinase activity and melanisation are stimulated by elevated intracellular levels of cyclic AMP1, apparently through the inactivation of an inhibitor of tyrosinase2. We initiated a series of experiments to identify the molecules controlling tyrosinase activity. Kuo and Greengard's observations on the widespread occurrence of cyclic AMP-dependent protein kinases throughout the phyla suggested that protein phosphorylation reactions might be involved3. We describe here a cell-free system in which tyrosinase is activated following the addition of a cyclic AMP-dependent protein kinase isolated from melanoma cells. The kinetics of the reaction in the cell-free system are similar to those in intact cells. The activation of tyrosinase is completely dependent on the protein kinase and is enhanced by cyclic AMP, ATP, and magnesium. The activation involves the removal of an inhibitor of tyrosinase; in addition, a phosphoprotein phosphatase is present which is distinct from the inhibitor but which appears to antagonize the kinase-mediated reaction.
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KÖRNER, A., PAWELEK, J. Activation of melanoma tyrosinase by a cyclic AMP-dependent protein kinase in a cell-free system. Nature 267, 444–447 (1977). https://doi.org/10.1038/267444a0
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DOI: https://doi.org/10.1038/267444a0
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