Winder A, Kobayashi T, Tsukamoto K, Urabe K, Aroca P, Kameyama K, Hearing V J
Sir William Dunn School of Pathology, University of Oxford, United Kingdom.
Cell Mol Biol Res. 1994;40(7-8):613-26.
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.
最近，几个对哺乳动物黑色素生成调控至关重要的基因已被克隆并进行了表征。它们定位于小鼠的白化、棕色和石板色基因座，并编码具有相似结构和特征但催化能力不同的蛋白质。白化基因座编码酪氨酸酶，一种具有三种不同黑色素生成功能的酶；棕色基因座编码TRP1（酪氨酸酶相关蛋白-1）；石板色基因座编码TRP2，另一种酪氨酸酶相关蛋白。TRP2作为多巴色素互变异构酶发挥作用，该酶可保留黑色素中的羧酸含量，若没有它，羧酸会自发丢失，而TRP1能够氧化TRP2产生的DHICA。在本研究中，我们使用了三种不同的系统（免疫亲和纯化的黑色素生成酶、突变黑素细胞和转染细胞）来研究这些蛋白质的酶促相互作用，以及它们在一个能显著延长其生理半衰期的复合物中的稳定性。将我们的结果外推至黑素细胞时，结果表明了这些蛋白质的催化功能，并提示了它们如何在黑素小体的黑色素生成复合物中稳定相互作用，以调节合成黑色素的数量和质量。
