Human tyrosinase related protein‐1 (TRP‐1) does not function as a DHICA oxidase activity in contrast to murine TRP‐1

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Abstract
Tyrosinase related protein‐1 is a melanocyte specific protein and a member of the tyrosinase gene family which also includes tyrosinase and TRP‐2 (DOPAchrome tautomerase). In murine melanocytes, TRP‐1 functions as a 5,6‐dihydroxyindole‐2‐carboxylic acid [DHICA] oxidase during the biosynthetic conversion of tyrosine to eumelanin and mutations affecting TRP‐1 result in the synthesis of brown rather than black pelage coloration. In this study, we examined the putative DHICA oxidase activity of TRP‐1 in human melanocytes using several approaches. We first utilized a line of cultured melanocytes established from a patient with a form of oculocutaneous albinism completely lacking expression of TRP‐1 (OCA3). This line of melanocytes endogenously exhibited the same amount of DHICA oxidase activity as control melanocytes expressing TRP‐1. In other experiments, cultured human fibroblasts were transfected with a cDNA for TRP‐1, in either the sense or antisense direction, or with the retroviral vector alone. TRP‐1 expression was induced in fibroblasts transfected with the TRP‐1 cDNA in the sense direction only. Although TRP‐1 was expressed by sense‐transfected cells, there was no significant DHICA oxidase activity above controls. These results demonstrate that human TRP‐1 does not use DHICA as a substrate for oxidation.