Mitogen and stress-activated protein kinase 1 mediates activation of Akt by ultraviolet B irradiation

In this study, we investigated the mechanism by which UVB irradiation activ ates Akt (also known as protein kinase B (PKB)) in mouse epidermal JB6 cell s. Treatment with a phosphatidylinositol 3-kinase inhibitor, LY 294002, or expression of a dominant negative mutant of p85 (regulatory component of ph osphatidylinositol 3-kinase) inhibited UVB-induced Akt activation. Interest ingly, Akt activation by UVB was attenuated by treatment with PD 98059, a s pecific mitogen-activated protein kinase/extracellular signal-regulated pro tein kinase (Erk) kinase 1 inhibitor, or SE 202190, a specific p38 kinase i nhibitor. Furthermore, the expression of a dominant negative mutant of Erk2 or p38 kinase, but not that of c-dun N-terminal kinase 1 (JNK1), blocked U VB-induced Akt activation. The expression of a dominant negative mutant of p85 or treatment with LY 294002 also inhibited UVB-induced Erk phosphorylat ion. The UVB-activated mitogen-activated protein kinase members, which were immunoprecipitated from cells exposed to UVB, did not phosphorylate Akt, I nstead, Akt was phosphorylated at both threonine 308 and serine 473 and act ivated by UVB-activated mitogen- and stress-activated protein kinase 1 (Msk 1). The expression of a Msk1 C-terminal kinase-dead mutant inhibited UVB-in duced phosphorylation and activation of Akt. These data thus suggested that UVB-induced Akt activation was mediated through Msk1, which is a downstrea m kinase of the Erk and p38 kinase signaling pathways.