Interleukin 1-β-induced protein kinase C-ζ activation is mimicked by exogenous phospholipase D

Abstract

Interleukin 1-β (IL1-β) 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-β 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-ζ (PKC-ζ) and the accumulation of a putative physiological PKC-ζ activator, phosphatidic acid. 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-ζ activation. In addition, we show that IL1-β stimulation of BOSC23 cells, transiently overexpressing PKC-ζ induced an increase in PKC-ζ autophosphorylation. These results give the first direct evidence that IL1-β can activate this atypical PKC isoform and suggest that this enzyme might be involved in mediating some of the biological effects induced by IL1-β.