We previously demonstrated that the oncogenic
kinase PAK4, which both
melanomas and normal melanocytes express at a very high level, is essential for their melanogenesis. In the present study, using the highly sensitive "Macaroni-Western" (IP-
ATP-Glo)
kinase assay, we investigated the melanogenic potential of another oncogenic
kinase PAK1, which
melanoma (B16F10) cells express only at a very minute level. After transfecting
melanoma cells with PAK1-shRNA for silencing PAK1 gene,
melanin content,
tyrosinase activity, and
kinase activity of PAK1 were compared between the wild-type and transfectants. We found that (i) PAK1 is significantly activated by melanogenic
hormones such as
IBMX (3-isobutyl-1-methyl xanthine) and α-
MSH (
melanocyte-stimulating hormone), (ii) silencing the endogenous PAK1 gene in
melanoma cells through PAK1-specific
shRNA reduces both
melanin content and
tyrosinase activity in the presence of both serum and melanogenic
hormones to the basal level, (iii) the exogenously added wild-type PAK1 in the
melanoma cells boosts the α-
MSH-inducible
melanin level by several folds without affecting the basal, and (iv) α-
MSH/
IBMX-induced melanogenesis hardly takes place in the absence of either serum or PAK1, clearly indicating that PAK1 is essential mainly for serum- and α-
MSH/
IBMX-dependent melanogenesis, but not the basal, in
melanoma cells. The outcome of this study might provide the first scientific basis for explaining why a wide variety of herbal PAK1-blockers such as CAPE (
caffeic acid phenethyl ester),
curcumin and
shikonin in
cosmetics are useful for skin-whitening.