ISSN:
1365-3083
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Protein kinase C (PKC)-activating phorbol esters are known to induce the expression of several genes in monocytic cells. As the effect of serine-threonine kinases, such as PKC, is often counteracted by specific protein phosphatases, we have now examined the role of phosphatases in the regulation of the phorbol ester (PM A)-induced interleukin-B(IL-1 B) gene expression in theTHP-1 monocytic leukaemia cell line. Okadaic acid (OA) is a potent tumour promoter, the function of which is based on its activity to inhibit the serine/threonine specific phosphatases 1 and 2A (PPI and PP2A, respectively). Thus, it mimicks or potentiates the action of PKC activators in several cell types. Our data demonstrate that alone OA induced a very weak expression of IL-B mRNA, but it strongly enhanced the PMA-induced IL-1BS expression. To analyse the site of action of OA, the cells were transiently transfected with a chloramphenicol acetyl transferase (CAT) –reporter plasmid containing the AP-1 binding site as the enhancer. Alone, OA was a weak inducer of CAT–activity in these cells, but again it strongly enhanced the PMA-induced response. Similar data were obtained with cells transfected with a reporter plasmid containing the PMA-responsive element (containing a putative AP-1 binding site) of the IL-B gene. Thus, these data indicate that the PMA-induced AP-1 enhancer activity, which is required for the expression of the IL–lB gene, is controlled in these cells by PPI and/or PP2A. As OA did not synergize with PMA in the induction of expression of genes encoding the AP-1 proteins (c–fos, c–jun, junB), it is likely that OA potentiates the AP-1 enhancer activity by its effect on protein phosphorylation.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1365-3083.1993.tb03243.x
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