TYROSINASE-RELATED PROTEIN-1 (TRP1) FUNCTIONS AS A DHICA OXIDASE IN MELANIN BIOSYNTHESIS
TYROSINASE-RELATED PROTEIN-1 (TRP1) FUNCTIONS AS A DHICA OXIDASE IN MELANIN BIOSYNTHESIS
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DOI：
10.1002/j.1460-2075.1994.tb06925.x
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发表时间：
1994-12-15
期刊：
影响因子：
11.4
通讯作者：
HEARING, VJ
中科院分区：
文献类型：
--
作者：
KOBAYASHI, T;URABE, K;HEARING, VJ
最近已经克隆了几个对哺乳动物黑色素产生的酶调节至关重要的基因，并将其定位于小鼠的白化病、棕色和板色基因座。所有这三个基因编码的蛋白质具有相似的结构和特征，但具有不同的催化能力;其中两个基因产物的功能以前已经被确定。白化病基因座编码酪氨酸酶，一种具有三种不同的黑素生成功能的酶，而板状基因座编码酪氨酸酶相关蛋白2（TRP 2），一种具有单一特异性但不同功能的酶，如多巴色素互变异构酶。虽然编码TRP 1的棕色基因座实际上是酪氨酸酶基因家族中第一个被克隆的成员，但其催化功能（导致产生黑色而不是棕色黑色素）一直存在争议。在这项研究中，我们使用了两种不同的技术（TRP 1在转染的成纤维细胞中的表达和TRP 1从黑素细胞中的免疫亲和纯化）来检查TRP 1的酶功能。数据表明，TRP 1的特定黑素生成功能是在黑素生物合成途径的下游点将5，6-二羟基吲哚-2-羧酸（DHICA）氧化为羧基化吲哚醌。这种酶活性似乎对DHICA进一步代谢为高分子量着色生物聚合物至关重要。
Several genes critical to the enzymatic regulation of melanin production in mammals have recently been cloned and mapped to the albino, brown and slaty loci in mice. All three genes encode proteins with similar structures and features, but with distinct catalytic capacities; the functions of two of those gene products have previously been identified. The albino locus encodes tyrosinase, an enzyme with three distinct melanogenic functions, while the slaty locus encodes tyrosinase-related protein 2 (TRP2), an enzyme with a single specific, but distinct, function as DOPAchrome tautomerase. Although the brown locus, encoding TRP1, was actually the first member of the tyrosinase gene family to be cloned, its catalytic function (which results in the production of black rather than brown melanin) has been in general dispute. In this study we have used two different techniques (expression of TRP1 in transfected fibroblasts and immunoaffinity purification of TRP1 from melanocytes) to examine the enzymatic function(s) of TRP1. The data demonstrate that the specific melanogenic function of TRP1 is the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) to a carboxylated indole-quinone at a downstream point in the melanin biosynthetic pathway. This enzyme activity appears to be essential to the further metabolism of DHICA to a high molecular weight pigmented biopolymer.