Activation of MAP kinase family members triggered by TPA or ionomycin occurs via the protein phosphatase 4 pathway in Jurkat leukemia T cells.
Protein phosphatase 4 (PP4) is a protein phosphatase 2A (PP2A)-related, okadaic acid-sensitive, serine/threonine protein phosphatase that shares 65% amino acid identity with PP2A. Numerous studies have shown that protein phosphatase is involved in the regulation of T cell signaling and activation. In this study, we investigated the effect of overexpression of PP4 on the expression of members of the MAP kinase family in Jurkat leukemia T cells, which had previously been stimulated with UV, 12-O-tetradecanoylphorbol-13-acetate (TPA), ionomycin and okadaic acid. We found that the overexpression of PP4 expressed relatively low activity in the absence of any kind of stimulation. However, TPA, UV or ionomycin treatment strongly increased the activity of PP4. In addition, Jurkat T cells, transfected with various expression plasmids and/or stimulated with TPA, UV or ionomycin strongly induced the c-Jun N-terminal kinase (JNK) and p38, whereas the extracellular signal-regulated kinase (ERK)-1/2 kinase pathway was weekly activated. Treatment of Jurkat T cells with okadaic acid, an inhibitor of PP2, also inhibited the increase of JNK and p38 activity induced by PP4. The effect of okadaic acid on the activity of PP4 was similar to that observed in Jurkat T cells treated with a dominant negative c-Jun (dn-jun). These results indicate that the activation of JNK and p38, but not ERKs, is a target for the PP4 activity in Jurkat leukemia T cells.
Biomedical Experimental Laboratory, Faculty of Sciences, University of Tarapaca, Arica, Chile. eparra@uta.cl
Eduardo
E
Parra
D061207:Calcium Ionophores / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D061207:Calcium Ionophores; D004791:Enzyme Inhibitors; D019319:Okadaic Acid; D015759:Ionomycin; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; C080406:protein phosphatase 4; D013755:Tetradecanoylphorbol Acetate