Syndecan-2 regulates melanin synthesis via protein kinase C βII-mediated tyrosinase activation.
Syndecan-2, a transmembrane heparan sulfate proteoglycan that is highly expressed in melanoma cells, regulates melanoma cell functions (e.g. migration). Since melanoma is a malignant tumor of melanocytes, which largely function to synthesize melanin, we investigated the possible involvement of syndecan-2 in melanogenesis. Syndecan-2 expression was increased in human skin melanoma tissues compared with normal skin. In both mouse and human melanoma cells, siRNA-mediated knockdown of syndecan-2 was associated with reduced melanin synthesis, whereas overexpression of syndecan-2 increased melanin synthesis. Similar effects were also detected in human primary epidermal melanocytes. Syndecan-2 expression did not affect the expression of tyrosinase, a key enzyme in melanin synthesis, but instead enhanced the enzymatic activity of tyrosinase by increasing the membrane and melanosome localization of its regulator, protein kinase CβII. Furthermore, UVB caused increased syndecan-2 expression, and this up-regulation of syndecan-2 was required for UVB-induced melanin synthesis. Taken together, these data suggest that syndecan-2 regulates melanin synthesis and could be a potential therapeutic target for treating melanin-associated diseases.
['Jung|Hyejung|H|', 'Chung|Heesung|H|', 'Chang|Sung Eun|SE|', 'Choi|Sora|S|', 'Han|Inn-Oc|IO|', 'Kang|Duk-Hee|DH|', 'Oh|Eok-Soo|ES|']
D000818:Animals D045744:Cell Line, Tumor D002462:Cell Membrane D004789:Enzyme Activation D000078404:Epidermal Cells D004817:Epidermis D005786:Gene Expression Regulation D006801:Humans D008543:Melanins D008544:Melanocytes D008545:Melanoma D020460:Melanosomes D051379:Mice D058990:Molecular Targeted Therapy D014442:Monophenol Monooxygenase D009363:Neoplasm Proteins D064546:Protein Kinase C beta D021381:Protein Transport D034622:RNA Interference D034741:RNA, Small Interfering D053669:Syndecan-2 D014466:Ultraviolet Rays D015854:Up-Regulation
syndecan-2 tyrosinase melanogenesis melanosome protein kinase C β