Abstract
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 previous work has shown that both Erks and JNKs are activated in cells in response to ultraviolet (UV) irradiation, most studies have focused only on the role of JNKs in UV-induced AP-1 activation. Hence, the role of Erks in UV-induced AP-1 activity is not well defined. We here have investigated this issue by using MAP kinase kinase (MEK1) inhibitor PD098059 and a dominant negative Erk2, as well as wild-type Erk2, in a JB6 cell model. PD098059 inhibited UVB- or UVC-induced AP-1 activity and phosphorylation of MEK1 and Erks, but not JNKs, in JB6 Cl 41 cells. Overexpression of wild-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 of a dominant negative Erk2 into Cl 41 cells significantly blocked the UV-induced Erks activation as well as the AP-1 activation. In contrast, overexpression 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. These results demonstrate that activation of Erks, in addition to the previously reported JNKs, is required for UV-induced AP-1 activation.
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Abbreviations
- UV:
-
ultraviolet
- AP-1:
-
activated protein-1
- EGF:
-
epidermal growth factor
- Erk:
-
extracellular signal-regulated protein kinase
- MAP kinase:
-
mitogen-activated protein kinase
- JNK:
-
c-Jun N-terminal kinase
- P+:
-
tumor promotion-sensitive
- P−:
-
tumor promotion-resistant
- TPA:
-
12-O-tetradecanoyl phorbol-13-acetate
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Acknowledgements
We thank Drs HHO Schmid and Douglas Bibus for their critical reading and Ms Jeanne Ruble for secretarial assistance. This work was supported in part by the Hormel Foundation.
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Huang, C., Ma, Wy. & Dong, Z. The extracellular-signal-regulated protein kinases (Erks) are required for UV-induced AP-1 activation in JB6 cells. Oncogene 18, 2828–2835 (1999). https://doi.org/10.1038/sj.onc.1202639
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DOI: https://doi.org/10.1038/sj.onc.1202639
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