title: Role and regulation of STAT3 phosphorylation at Ser727 in melanocytes and melanoma cells.
abstract: The transcription factor signal transducer and activator of transcription 3 (STAT3) has two important phosphorylation sites, Tyr705 and Ser727, for its activation. Ser727 phosphorylation has been considered to be a secondary event after Tyr705 phosphorylation. In this study, the role and regulation of Ser727 phosphorylation in STAT3 in melanocytic cells were examined. STAT3 was phosphorylated on Ser727 in the absence of Tyr705 phosphorylation in melanocytes. 12-O-tetradecanoylphorbol-13-acetate-induced increase in cell survival activity and nuclear translocation of STAT3 was associated with Ser727 phosphorylation. Ser727 was constitutively phosphorylated in all melanoma cell lines examined irrespective of Tyr705 phosphorylation. The possible involvement of Ser727 phosphorylation in STAT3 in cell survival activity and nuclear translocation of STAT3 in melanocytes was demonstrated also in melanoma cells. The constitutive Ser727 phosphorylation in melanoma cells was partially mediated by the B-Raf-MEK-ERK1/2 pathway. Immunohistochemical studies on specimens of primary lesions of acral lentiginous melanoma revealed that Ser727 phosphorylation precedes Tyr705 phosphorylation in the early stages of melanoma progression. Our results indicate that Ser727 phosphorylation on STAT3 is not necessarily a secondary event after Tyr705 phosphorylation and suggest that it has a role in the regulation of cell survival activity and nuclear translocation of STAT3 in melanocytic cells.
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Oka
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Fukami
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
mesh_terms: D021581:Active Transport, Cell Nucleus; D045744:Cell Line, Tumor; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D006801:Humans; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D012694:Serine; D004247:DNA