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Biochem J. Jan 15, 1997; 321(Pt 2): 497–501.
PMCID: PMC1218096

Interleukin 1-beta-induced protein kinase C-zeta activation is mimicked by exogenous phospholipase D.

Abstract

Interleukin 1-beta (IL1-beta) is a pleiotropic cytokine that stimulates a number of signal transduction pathways in cells, leading to different cellular responses. In this study we investigated the signal transduction pathways activated by IL1-beta in two different human cell lines: RD/TE671, a rhabdomyosarcoma, and EJ, a bladder-derived carcinoma. We showed that this cytokine induced the activation of protein kinase C-zeta (PKC-zeta) and the accumulation of a putative physiological PKC-zeta activator, phosphatidic acid [Limatola, Schaap, Moolenaar and van Blitterswijk (1994) Biochem. J. 304, 1001-1008]. Exogenously supplied phospholipase D, which generated cellular phosphatidic acid, was able to mimic the cytokine effect, supporting the hypothesis that this lipid second messenger might contribute to cytokine-induced PKC-zeta activation. In addition, we show that IL1-beta stimulation of BOSC23 cells, transiently overexpressing PKC-zeta, induced an increase in PKC-zeta autophosphorylation. These results give the first direct evidence that IL1-beta can activate this atypical PKC isoform and suggest that this enzyme might be involved in mediating some of the biological effects induced by IL1-beta.

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