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 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.
Limatola
C
C
Biophysics Laboratory, Centro Ricerca Sperimentale IRE, Rome, Italy.
Barabino
B
B
Nista
A
A
Santoni
A
A
D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D012208:Rhabdomyosarcoma; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000099221:Protein Kinase C zeta
D007375:Interleukin-1; D007527:Isoenzymes; D010712:Phosphatidic Acids; D010739:Phospholipase D; D011493:Protein Kinase C; D013108:Sphingomyelin Phosphodiesterase; D000099221:Protein Kinase C zeta