International Immunology, Vol. 15, No. 9, pp. 1089-1098,
September 2003
© 2003 Japanese Society for Immunology
Protein kinase Cß1, a major regulator of TCR–CD28-activated signal transduction leading to IL-2 gene transcription and secretion
1 Institute of Pharmacology, Medical School Hannover, 30623 Hannover, Germany
The first two authors contributed equally to this work
Correspondence to: M. Szamel; E-mail: Szamel.Marta{at}MH-Hannover.de
Transmitting editor: T. Hünig
The aim of this study was to investigate the influence of protein kinase C (PKC) 
and ß on the TCR–CD28-stimulated protein kinase cascades participating in regulation of IL-2 gene transcription and secretion. Inhibition of the synthesis of PKC and ß by specific phosphorothioate-modified antisense oligonucleotides (ODN) resulted in suppression of phosphorylation and activation of Raf-1, mitogen-activated extracellular-regulated kinase kinases and extracellular-regulated kinases in stimulated Jurkat T cells. Furthermore, a marked reduction of I
B kinase--catalyzed IB phosphorylation was observed in both PKC- and ß-specific antisense oligonucleotide-treated cells. In sharp contrast, TCR–CD28-stimulated phosphorylation and activation of the Jun-N-terminal kinase (JNK) cascade was specifically suppressed upon treatment with PKCß-specific antisense ODN, suggesting that PKCß was a specific upstream regulator of the JNK protein kinase cascade. Significant inhibition of high-affinity NF-AT binding and transactivation, IL-2 gene expression, reduction of IL-2 mRNA synthesis, and, most impressively, a complete suppression of IL-2 secretion were observed in PKCß antisense ODN-treated cells. The data indicate a highly specific function of PKCß for regulation of TCR–CD28 induced-signaling, IL-2 gene expression and secretion in Jurkat T cells.
Keywords: cytokine, protein kinase/phosphatase, signal transduction, T lymphocyte, transcription factor