CALCIUM SIGNALS AND PROTEIN-TYROSINE KINASES ARE REQUIRED FOR THE INDUCTION OF C-JUN IN JURKAT CELLS STIMULATED BY THE T-CELL-RECEPTOR COMPLEX AND OXIDATIVE SIGNALS

The regulation of c-jun plays an important role in T cell activation, proliferation, and expression of interleukin-2, In the present study, we determined whether Ca2+ signals and the activity of protein tyrosin e kinases (PTKs) were required for the induction of c-jun in Jurkat ce lls stimulated with cross-linked anti-T cell receptor/CD3 antibodies o r exposed to oxidative stress in the form of micromolar concentrations of H2O2. Jurkat cells exhibited rapid elevations in intracellular cal cium [Ca2+](i) levels in response to H2O2 and cross-linked anti-CD3 an tibodies that mainly reflected the influx of extracellular Ca2+. The C a2+ flux in response to oxidative signals was distinguished by an exqu isite sensitivity to inhibition with Ni2+, suggesting the involvement of cation channels, PTK activity was needed for [Ca2+](i) elevations i n response to both oxidative and anti-CD3 signals, although H2O2 induc tion of [Ca2+](i) increases was more resistant to inhibition by genist ein than anti-CD3 [Ca2+](i) responses, Both oxidative signals and anti -CD3 stimulation induced increased levels of c-jun and c-fos mRNA. The increased expression of c-jun with H2O2 was preceded by [Ca2+](i) inc reases and accompanied by activation of c-Jun aminoterminal kinases (J NKs), as well as increased AP-1 binding activity, Induction of c-jun w ith oxidative signals and anti-CD3 was also shown to be crucially depe ndent on [Ca2+](i) elevations because the chelation of [Ca2+](i) with BAPTA resulted in a dose-dependent inhibition of c-jun expression, Fur thermore, inhibition studies demonstrated that the optimal induction o f c-jun mRNA in response to oxidative signals required PTK as well as protein kinase C (PKC), Thus, these findings suggest that both [Ca2+]( i) signals and the activity of PTKs are essential for the optimal expr ession of c-jun in response to TCR/CD3 signals and changes in redox po tentials.