Interleukin-1-induced signaling in T-cells. Evidence for the involvement of phosphatases PP1 and PP2A in regulating protein kinase C-mediated protein phosphorylation and interleukin-2 synthesis.
Binding of human recombinant interleukin-1 beta (IL-1 beta) to the cell surface receptors of EL-4 6.1 murine T-cells results in enhanced phosphorylation of several cellular proteins. Staurosporine abolished the enhanced phosphorylation in response to IL-1 for some of these proteins, suggesting that protein kinase C (PKC) was at least partially responsible. PKC-beta was translocated from the cytosol to the plasma membrane between 2 and 15 min after IL-1 binding. Activation of PKC-beta was enhanced by the protein phosphatase inhibitor okadaic acid. In fact, okadaic acid inhibited dephosphorylation of the PKC-specific peptide GS (Pro-Leu-Ser-Arg-Thr-Leu-Ser-Val-Ala-Ala-Lys-Lys). On the other hand, okadaic acid also led to elevation of IL-1-induced trans/autophosphorylation of PKC-beta. Accordingly, IL-1 induction of interleukin-2 synthesis was markedly enhanced by okadaic acid in EL-4 cells. These data suggest that activation of PKC-beta contributes to enhanced phosphorylation of cellular proteins in IL-1-treated cells and support the importance of protein phosphorylation and dephosphorylation in the regulation of IL-1-induced IL-2 synthesis in EL-4 6.1 T-cells.
Kracht
M
M
Institute of Molecular Pharmacology, Medical School of Hannover, Germany.
Heiner
A
A
Resch
K
K
Szamel
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D004789:Enzyme Activation; D004988:Ethers, Cyclic / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis*; D051379:Mice; D008969:Molecular Sequence Data; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D004988:Ethers, Cyclic; D007375:Interleukin-1; D007376:Interleukin-2; D019319:Okadaic Acid; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases