INTERLEUKIN 1-BETA-INDUCED PROTEIN-KINASE C-ZETA ACTIVATION IS MIMICKED BY EXOGENOUS PHOSPHOLIPASE-D

Interleukin 1-beta (IL1-beta) is a pleiotropic cytokine that stimulate s a number of signal transduction pathways in cells, leading to differ ent cellular responses. In this study we investigated the signal trans duction pathways activated by IL1-beta in two different human cell lin es: 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 PK C-zeta activator, phosphatidic acid [Limatola, Schaap, Moolenaar and v an Blitterswijk (1994) Biochem. J. 304, 1001-1008]. Exogenously suppli ed phospholipase D, which generated cellular phosphatidic acid, was ab le to mimic the cytokine effect, supporting the hypothesis that this l ipid second messenger might contribute to cytokine-induced PKC-zeta ac tivation. In addition, we show that IL1-beta stimulation of BOSC23 cel ls, transiently overexpressing PKC-zeta induced an increase in PKC-zet a autophosphorylation. These results give the first direct evidence th at IL1-beta can activate this atypical PKC isoform and suggest that th is enzyme might be involved in mediating some of the biological effect s induced by IL1-beta.