p38/SAPK2-dependent gene expression in Jurkat T cells.

The stress-activated protein kinase p38/SAPK2 is known to regulate the activity of transcription factors and to control expression of several genes at the transcriptional or post-transcriptional level. In order to identify genes whose expression is under the control of p38/SAPK2 activity, we have compared the mRNA levels of a pattern of 588 genes between human Jurkat T cells with anisomycin-activated p38/SAPK2 and cells in which p38/SAPK2 was inhibited by the compound SB203580. Genes strongly expressed at the transcript level as a result of p38/SAPK2 activation are the transcription factors c-jun, fos-related antigen 1 (fra-1), the growth-arrest and DNA-damage gene gadd153 and early-growth-related gene 1 (egr-1) as well as the c-srk kinase csk and the nucleotide exchange factor ras-GRF. mRNAs significantly down-regulated include the insulin receptor IR, the adapter grb2, the transcription factor c-myc and the defender against apoptotic death, dad-1. For six selected genes, p38/SAPK2-regulated expression was confirmed and further analysed by Northern blot experiments, demonstrating a complex regulation of these genes under stress conditions.