title: The serum/PDGF-dependent "melanogenic" role of the minute level of the oncogenic kinase PAK1 in melanoma cells proven by the highly sensitive kinase assay.
abstract: 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.
authors.affiliation: PAK Research Center, University of the Ryukyus.
authors.forename: Pham Thi
authors.initials: PT
authors.lastname: Be Tu
authors.forename: Binh Cao Quan
authors.initials: BC
authors.lastname: Nguyen
authors.forename: Shinkichi
authors.initials: S
authors.lastname: Tawata
authors.forename: Cheong-Yong
authors.initials: CY
authors.lastname: Yun
authors.forename: Eung Gook
authors.initials: EG
authors.lastname: Kim
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maruta
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D008543:Melanins / Q000378:metabolism; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D034622:RNA Interference; D054462:p21-Activated Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D008543:Melanins; D010982:Platelet-Derived Growth Factor; D009074:Melanocyte-Stimulating Hormones; C515905:Pak1 protein, mouse; D054462:p21-Activated Kinases; D015056:1-Methyl-3-isobutylxanthine