Inhibition of the Mitogen-activated Protein Kinase Pathway Triggers B16 Melanoma Cell Differentiation

• DOI: 10.1074/jbc.273.16.9966
• Publication Date: 2002-07-26T15:04:43Z
• Authors: Walter Englaro; Corine Bertolotto; Roser Buscà; Anne Brunet; Gilles Pagès; Jean-Paul Ortonne; Robert Ballotti
• Keywords: c-Raf; ASK1

In B16 melanoma cells, mitogen-activated protein (MAP) kinases are activated during cAMP-induced melanogenesis (Englaro, W., Rezzonico, R., Durand-Clément, M., Lallemand, D., Ortonne, J. P., and Ballotti, R. (1995) <i>J. Biol. Chem.</i>270, 24315–24320). To establish the role of MAP in melanogenesis, we studied effects a specific kinase (MEK) inhibitor PD 98059 on different melanogenic parameters. We showed that inhibits activation extracellular signal-regulated 1 by cAMP, but does not impair cAMP either morphological differentiation, characterized an increase dendrite outgrowth, or up-regulation tyrosinase is key enzyme melanogenesis. On contrary, promotes itself cell dendricity increases amount activity. Moreover, down-regulation pathway 98059, with dominant negative mutants p21^ras MEK, triggers stimulation promoter activity enhances effect this parameter. Conversely, pathway, using constitutive active leads to inhibition basal gene transcription. These results demonstrate required for Furthermore, induces while sustained impairs cAMP-elevating agents.