PP2A and DUSP6 are involved in sphingosylphosphorylcholine-induced hypopigmentation

详细信息    查看全文

• 作者：Hyo-Soon Jeong (1)
  Kyoung-Chan Park (2)
  Dong-Seok Kim (1) ds_kim@cau.ac.kr
• 关键词：ERK – ; Melanocytes – ; DUSP6 – ; PP2A – ; Sphingosylphosphorylcholine
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2012
• 出版时间：August 2012
• 年：2012
• 卷：367
• 期：1-2
• 页码：43-49
• 全文大小：434.4 KB
• 参考文献：1. Desai NN, Spiegel S (1991) Sphingosylphosphorylcholine is a remarkably potent mitogen for a variety of cell lines. Biochem Biophys Res Commun 181:361–366
  2. Desai NN, Carlson RO, Mattie ME, Olivera A, Buckley NE, Seki T, Brooker G, Spiegel S (1993) Signaling pathways for sphingosylphosphorylcholine-mediated mitogenesis in Swiss 3T3 fibroblasts. J Cell Biol 121:1385–1395
  3. Kim DS, Park SH, Kwon SB, Park ES, Huh CH, Youn SW, Park KC (2006) Sphingosylphosphorylcholine-induced ERK activation inhibits melanin synthesis in human melanocytes. Pigment Cell Res 19:146–153
  4. Kim DS, Park SH, Kwon SB, Kwon NS, Park KC (2010) Sphingosylphosphorylcholine inhibits melanin synthesis via pertussis toxin-sensitive MITF degradation. J Pharm Pharmacol 62:181–187
  5. Costin GE, Hearing VJ (2007) Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J 21:976–994
  6. Levy C, Khaled M, Fisher DE (2006) MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol Med 12:406–414
  7. Villareal MO, Han J, Yamada P, Shigemori H, Isoda H (2010) Hirseins inhibit melanogenesis by regulating the gene expressions of Mitf and melanogenesis enzymes. Exp Dermatol 19:450–457
  8. Zhang W, Liu HT (2002) MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res 12:9–18
  9. Chuderland D, Seger R (2005) Protein–protein interactions in the regulation of the extracellular signal-regulated kinase. Mol Biotechnol 29:57–74
  10. Kim DS, Hwang ES, Lee JE, Kim SY, Kwon SB, Park KC (2003) Sphingosine-1-phosphate decreases melanin synthesis via sustained ERK activation and subsequent MITF degradation. J Cell Sci 116:1699–1706
  11. Englaro W, Bertolotto C, Busca R, Brunet A, Pages G, Ortonne JP, Ballotti R (1998) Inhibition of the mitogen-activated protein kinase pathway triggers B16 melanoma cell differentiation. J Biol Chem 273:9966–9970
  12. Seufferlein T, Rozengurt E (1995) Sphingosylphosphorylcholine activation of mitogen-activated protein kinase in Swiss 3T3 cells requires protein kinase C and a pertussis toxin-sensitive G protein. J Biol Chem 270:24334–24342
  13. Higuchi K, Kawashima M, Ichikawa Y, Imokawa G (2003) Sphingosylphosphorylcholine is a melanogenic stimulator for human melanocytes. Pigment Cell Res 16:670–678
  14. Gomez N, Cohen P (1991) Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases. Nature 353:170–173
  15. Anderson NG, Maller JL, Tonks NK, Sturgill TW (1990) Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase. Nature 343:651–653
  16. Zhou B, Wang ZX, Zhao Y, Brautigan DL, Zhang ZY (2002) The specificity of extracellular signal-regulated kinase 2 dephosphorylation by protein phosphatases. J Biol Chem 277:31818–31825
  17. Ng DC, Bogoyevitch MA (2000) The mechanism of heat shock activation of ERK mitogen-activated protein kinases in the interleukin 3-dependent ProB cell line BaF3. J Biol Chem 275:40856–40866
  18. Kim DS, Park SH, Kwon SB, Youn SW, Park ES, Park KC (2005) Heat treatment decreases melanin synthesis via protein phosphatase 2A inactivation. Cell Signal 17:1023–1031
  19. Jeffrey KL, Camps M, Rommel C, Mackay CR (2007) Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses. Nat Rev Drug Discov 6:391–403
  20. Bermudez O, Jouandin P, Rottier J, Bourcier C, Pages G, Gimond C (2011) Post-transcriptional regulation of the DUSP6/MKP-3 phosphatase by MEK/ERK signaling and hypoxia. J Cell Physiol 226:276–284
  21. Molina G, Vogt A, Bakan A, Dai W, Queiroz de Oliveira P, Znosko W, Smithgall TE, Bahar I, Lazo JS, Day BW, Tsang M (2009) Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages. Nat Chem Biol 5:680–687
  22. Dooley TP, Gadwood RC, Kilgore K, Thomasco LM (1994) Development of an in vitro primary screen for skin depigmentation and antimelanoma agents. Skin Pharmacol 7:188–200
  23. Tsuboi T, Kondoh H, Hiratsuka J, Mishima Y (1998) Enhanced melanogenesis induced by tyrosinase gene-transfer increases boron-uptake and killing effect of boron neutron capture therapy for amelanotic melanoma. Pigment Cell Res 11:275–282
  24. Neviani P, Santhanam R, Trotta R, Notari M, Blaser BW, Liu S, Mao H, Chang JS, Galietta A, Uttam A, Roy DC, Valtieri M, Bruner-Klisovic R, Caligiuri MA, Bloomfield CD, Marcucci G, Perrotti D (2005) The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein. Cancer Cell 8:355–368
  25. Kim DS, Kim SY, Chung JH, Kim KH, Eun HC, Park KC (2002) Delayed ERK activation by ceramide reduces melanin synthesis in human melanocytes. Cell Signal 14:779–785
  26. Karlsson AM, Lerner MR, Unett D, Lundstrom I, Svensson SP (2000) Melatonin-induced organelle movement in melanophores is coupled to tyrosine phosphorylation of a high molecular weight protein. Cell Signal 12:469–474
  27. Xu Y, Zhu K, Hong G, Wu W, Baudhuin LM, Xiao Y, Damron DS (2000) Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1. Nat Cell Biol 2:261–267
  28. Xu Y, Zhu K, Hong G, Wu W, Baudhuin LM, Xiao Y, Damron DS (2006) Retraction; sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1. Nat Cell Biol 8:299
  29. Nixon GF, Mathieson FA, Hunter I (2008) The multi-functional role of sphingosylphosphorylcholine. Prog Lipid Res 47:62–75
• 作者单位：1. Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong Dongjak-gu, Seoul, 156-756 Republic of Korea2. Department of Dermatology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Kyoungki-do 463-707, Republic of Korea
• ISSN：1573-4919

文摘

Activation of extracellular signal-related kinase (ERK) is involved in decreased melanogenesis by sphingosylphosphorylcholine (SPC). In the present study, we confirmed that SPC activated ERK and that a specific inhibitor of the ERK pathway (PD98059) recovered SPC-induced hypopigmentation. Moreover, we found that SPC significantly reduces protein phosphatase 2A (PP2A) activity in Mel-Ab cells, and that PP2A activator treatment abrogated SPC-induced hypopigmentation. We determined that α-melanocyte-stimulating hormone (α-MSH) increased the expression of dual-specificity phosphatase 6 (DUSP6), an ERK phosphatase, in a time-dependent manner. In contrast, SPC decreased the level of DUSP6 in Mel-Ab cells. Furthermore, inhibiting DUSP6 increased ERK activation and subsequently augmented the SPC-induced hypopigmenting effects. Taken together, our data suggest that SPC-induced phosphatase inhibition is also responsible for the hypopigmentary effects.