Mitogen- and stress-activated protein kinase 1 is critical for interleukin-1-induced, CREB-mediated, c-fos gene expression in keratinocytes

Oncogene
M SchillerA Mauviel

Abstract

c-fos, which encodes a transcription factor of the AP-1 family, is a prototypical immediate-early gene induced by a number of proinflammatory cytokines including interleukin-1 (IL-1), the latter being an important regulator of skin homeostasis. Using the human keratinocyte cell line HaCaT as an in vitro model, we dissected the molecular pathways leading to IL-1-induced c-fos gene induction. Phosphorylation of the transcription factor cAMP response element binding protein (CREB) at Ser133 was found to be essential for IL-1-induced c-fos gene induction and was closely paralleled by protein kinase A (PKA) activation. In contrast to other cell types, the cyclooxygenase/prostaglandin pathway, known to activate the cAMP/PKA cascade, plays little, if any, role in c-fos expression downstream of the IL-1 receptor in keratinocytes. Simultaneous activation of several of the mitogen-activated protein kinase (MAPK) cascades occurred in response to IL-1, but each differentially contributed to c-fos induction by IL-1, with the p38/MAPK being the most crucial of all, the extracellular signal-regulated kinase pathway contributing in an additive manner and the Jun N-terminal kinase pathway playing little, if any, role. We also demonstrate that p...Continue Reading

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Citations

Apr 27, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jeongim HaHong-Hee Kim
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