Functional properties of cloned melanogenic proteins.
Several genes critical to the regulation of melanin production in mammals have recently been cloned and characterized. They map to the albino, brown, and slaty loci in mice, and encode proteins with similar structures and features, but with distinct catalytic capacities. The albino locus encodes tyrosinase, an enzyme with three distinct catalytic activities--tyrosine hydroxylase, 3,4-dihydroxyphenylalanine (DOPA) oxidase and DHI (5,6-dihydroxyindole) oxidase. The brown locus encodes TRP-1 (tyrosinase-related protein-1), which has the same, but greatly reduced, catalytic potential. The slaty locus encodes TRP-2, another tyrosinase related-protein, which has DOPAchrome tautomerase activity. In this study we have examined the enzymatic interactions of these proteins, and their regulation by a novel melanogenic inhibitor. We observed that tyrosinase activity is more stable in the presence of TRP-1 and/or TRP-2, but that the catalytic function of TRP-2 is not affected by the presence of TRP-1 or tyrosinase. Other factors also may influence melanogenesis and a unique melanogenic inhibitor suppresses tyrosinase and DOPAchrome tautomerase activities, but does not affect the spontaneous rate of DOPAchrome decarboxylation to DHI. The results demonstrate the catalytic functions of these proteins and how they stably interact within a melanogenic complex in the melanosome to regulate the quantity and quality of melanin synthesized by the melanocyte.
Hearing
V J
VJ
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Tsukamoto
K
K
Urabe
K
K
Kameyama
K
K
Montague
P M
PM
Jackson
I J
IJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000502:physiology; D008543:Melanins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D008544:Melanocytes / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D008562:Membrane Glycoproteins; D051379:Mice; D008970:Molecular Weight; D014442:Monophenol Monooxygenase / Q000502:physiology; D010088:Oxidoreductases; D011506:Proteins / Q000502:physiology
D008543:Melanins; D008562:Membrane Glycoproteins; D011506:Proteins; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase