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Open Access research with a European policy impact...

The Strathprints institutional repository is a digital archive of University of Strathclyde's Open Access research outputs. Strathprints provides access to thousands of Open Access research papers by Strathclyde researchers, including by researchers from the European Policies Research Centre (EPRC).

EPRC is a leading institute in Europe for comparative research on public policy, with a particular focus on regional development policies. Spanning 30 European countries, EPRC research programmes have a strong emphasis on applied research and knowledge exchange, including the provision of policy advice to EU institutions and national and sub-national government authorities throughout Europe.

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Proteinase-activated receptor-2-mediated activation of stress-activated protein kinases and inhibitory kappa b kinases in NCTC 2544 keratinocytes

Kanke, T. and MacFarlane, S.R. and Seatter, M.J. and Davenport, E.L. and Paul, A. and McKenzie, R.C. and Plevin, R.J. (2001) Proteinase-activated receptor-2-mediated activation of stress-activated protein kinases and inhibitory kappa b kinases in NCTC 2544 keratinocytes. Journal of Biological Chemistry, 276 (34). pp. 31657-31666. ISSN 1083-351X

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In this study we examined the regulation of the stress-activated protein (SAP) kinases and inhibitory κB kinases (IKKs) through stimulation of the novel G-protein-coupled receptor proteinase-activated receptor-2 in the human keratinocyte cell line NCTC2544. Trypsin and the peptide SLIGKV stimulated a time-dependent increase in both c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activity. Trypsin also stimulated NFκB-DNA binding and the activation of the upstream kinases IKKα and -β. Phorbol 12-myristate 13-acetate also strongly activated both SAP kinases and IKK isoforms, suggesting the potential for a protein kinase C-mediated regulatory mechanism underlying the effects of trypsin. Pre-incubation with selective protein kinase C (PKC) inhibitors GF109203X and Gö6983, or transfection of dominant negative (DN)-PKCα, abolished phorbol 12-myristate 13-acetate-mediated c-Jun N-terminal kinase activity, although it only partially inhibited the response to trypsin. In contrast, Gö6983 reduced trypsin-stimulated p38 mitogen-activated protein kinase activity to a greater extent than GF109203X, although DN-PKCα or PKCζ had no substantial effect. Additionally, inhibitors of PKC partially reduced trypsin-stimulated IKKα activity but abolished that of IKKβ, whereas DN-PKCα but not DN-PKCζ substantially reduced trypsin-stimulated Flag-IKKβ activity. This study shows for the first time proteinase-activated receptor-2-mediated stimulation of both SAP kinase and IKK signaling and differing roles for PKC isoforms in the regulation of each pathway.