MEK7-dependent activation of p38 MAP kinase in keratinocytes

Previous studies suggest that a PKC/Ras/MEKK1 cascade regulates involucrin (hINV) gene expression in human epidermal keratinocytes. MEK7, which is exp ressed in epidermis, has been identified as a member of this cascade (Efimo va, T., LaCelle, P., Welter, J. F., and Eckert, R. L. (1998) J. Biol. Chem. 273, 24387-24395 and Efimova, T., and Eckert, R. L. (2000) J. Biol. Chem. 275, 1601-1607). However, the kinase that functions downstream of MEK7 has not been identified. Our present studies show that MEK7 expression in kerat inocytes markedly activates p38 alpha and modestly activates JNK. Activatio n of p38 MAPK by MEK7 is a novel finding, as previous reports have assigned MEK7 as a JNK regulator. We also demonstrate that this regulation is physi ologically important, as the p38 alpha- and JNK-dependent activities regula te hINV promoter activity and expression of the endogenous hINV gene.