title: The tyrosinase gene family--interactions of melanogenic proteins to regulate melanogenesis.
abstract: 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 melanogenic functions, the brown locus encodes TRP1 (tyrosinase-related protein-1), and the slaty locus encodes TRP2, another tyrosinase related-protein. TRP2 functions as DOPAchrome tautomerase, an enzyme that preserves the carboxylic acid content of melanins, which would be spontaneously lost in its absence, while TRP1 is able to oxidize the DHICA produced by TRP2. In this study we have used three different systems (immune-affinity purified melanogenic enzymes, mutant melanocytes, and transfected cells) to examine the enzymatic interactions of these proteins, and their stabilization in a complex which significantly increases their physiological half-life. When extrapolated to the melanocyte, our results demonstrate the catalytic functions of these proteins and suggest how they might stably interact within a melanogenic complex in the melanosome to regulate the quantity and quality of melanin synthesized.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Winder
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: K
authors.initials: K
authors.lastname: Urabe
authors.forename: P
authors.initials: P
authors.lastname: Aroca
authors.forename: K
authors.initials: K
authors.lastname: Kameyama
authors.forename: V J
authors.initials: VJ
authors.lastname: Hearing
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D002460:Cell Line; D006706:Homeostasis; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000096:biosynthesis / Q000378:metabolism*; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000378:metabolism; D008546:Melanoma, Experimental; D008562:Membrane Glycoproteins; D051379:Mice; D014442:Monophenol Monooxygenase / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism*; D005810:Multigene Family; D010088:Oxidoreductases; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D008543:Melanins; D008562:Membrane Glycoproteins; D011506:Proteins; D010088:Oxidoreductases; D014446:Tyrosine 3-Monooxygenase; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase