MITOGEN STIMULATION OF T-CELLS INCREASES C-FOS AND C-JUN PROTEIN-LEVELS, AP-1 BINDING AND AP-1 TRANSCRIPTIONAL ACTIVITY

被引:28
作者
KVANTA, A
KONTNY, E
JONDAL, M
OKRET, S
FREDHOLM, BB
机构
[1] KAROLINSKA INST,DEPT IMMUNOL,S-10401 STOCKHOLM 60,SWEDEN
[2] KAROLINSKA INST,DEPT MED NUTR,S-10401 STOCKHOLM 60,SWEDEN
关键词
T-CELL ACTIVATION; T-CELL RECEPTOR; PROTEIN KINASE-C; TRANSCRIPTION FACTOR; GENE REGULATION;
D O I
10.1016/0898-6568(92)90067-I
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have analysed the effect of mitogenic lectins on c-Fos and c-Jun protein levels as well as on activator protein-1 (AP-1) binding and enhancer activity in Jurkat T-cells, Both c-Fos and c-Jun protein levels were increased after Con A and PHA stimulation. Since T-cell stimulation increases both intracellular Ca2+ and cAMP levels and activates protein kinase C (PKC), the possible involvement of these intracellular messengers in c-Fos and c-Jun induction was tested. PMA, which directly activates PKC. mimicked the effect of the lectins on c-Fos and c-Jun, but elevation of either intracellular Ca2+ or cAMP levels had little or no effect. The mitogen-induced increase of c-Fos and c-Jun immunoreactivity was inhibited by H-7, a kinase inhibitor with relatively high specificity for PKC, and less efficiently by H-8, a structurally related kinase inhibitor less active on PKC, but more active on cyclic nucleotide-dependent kinases. Con A stimulation was found to increase both binding of AP-I to the AP-1 consensus sequence, TRE, and AP-1 enhancer activity, in Jurkat cells. PMA was also found to increase the AP-1 enhancer activity, whereas elevation of Ca2+ or cAMP had only minor effects. We conclude that stimulation with mitogenic lectins is sufficient to increase both c-Fos and c-Jun protein levels, AP-1 binding and AP-1 enhancer activity in Jurkat cells and that they act via mechanisms that could involve the activation of PKC.
引用
收藏
页码:275 / 286
页数:12
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