The extracellular-signal-regulated protein kinases (Erks) are required forUV-induced AP-1 activation in JB6 cells

Mitogen activated protein (MAP) kinase belongs to a large family of serine/ threonine protein kinases, including extracellular-signal-regulated protein kinases (Erks), P38 kinase and c-Jun N-terminal kinases (JNKs), Although p revious work has shown that both Erks and JNKs are activated in cells in re sponse to ultraviolet (UV) irradiation, most studies have focused only on t he role of JNKs in UV-induced AP-1 activation. Hence, the role of Erks in U V-induced AP-1 activity is not well defined. We here have investigated this issue by using MAP kinase kinase (MEK,) inhibitor PD098059 and a dominant negative Erk2, as a ell as wild-type Erk2, in a JB6 cell model. PD098059 in hibited UVB- or UVC-induced AP-1 activity and phosphorylation of MEK1, and Erks, but not JNKs, in JB6 Cl 41 cells. Overexpression of mild-type Erk2 in Cl 30.7b cells that contain small amounts of Erks caused a 46.6- or 138.1- fold increase of AP-1 activity by UVB and UVC, respectively; introduction o f a dominant negative Erk2 into Cl 41 cells significantly blocked the UV-in duced Erks activation as well as the AP-1 activation. In contrast, overexpr ession of wild-type Erk2 in Cl 30.7b cells and dominant negative Erk2 in Cl 41 cells did not show a marked influence on the phosphorylation of JNKs, T hese results demonstrate that activation of Erks, in addition to the previo usly reported JNKs, is required for UV-induced AP-1 activation.