title: 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.
abstract: 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 tyrosine kinases (PTKs) were required for the induction of c-jun in Jurkat cells stimulated with cross-linked anti-T cell receptor/CD3 antibodies or exposed to oxidative stress in the form of micromolar concentrations of H2O2. Jurkat cells exhibited rapid elevations in intracellular calcium [Ca2+]i levels in response to H2O2 and cross-linked anti-CD3 antibodies that mainly reflected the influx of extracellular Ca2+. The Ca2+ flux in response to oxidative signals was distinguished by an exquisite sensitivity to inhibition with Ni2+, suggesting the involvement of cation channels. PTK activity was needed for [Ca2+]i elevations in response to both oxidative and anti-CD3 signals, although H2O2 induction of [Ca2+]i increases was more resistant to inhibition by genistein 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 increases and accompanied by activation of c-Jun aminoterminal kinases (JNKs), as well as increased AP-1 binding activity. Induction of c-jun with oxidative signals and anti-CD3 was also shown to be crucially dependent on [Ca2+]i elevations because the chelation of [Ca2+]i with BAPTA resulted in a dose-dependent inhibition of c-jun expression. Furthermore, inhibition studies demonstrated that the optimal induction of 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 expression of c-jun in response to TCR/CD3 signals and changes in redox potentials.
authors.affiliation: Department of Medical Biochemistry, William H. Davis Medical Research Center, Ohio State University, Columbus 43210-1228, USA.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.forename: K V
authors.initials: KV
authors.lastname: Hackshaw
authors.forename: R L
authors.initials: RL
authors.lastname: Whisler
mesh_terms: D000917:Antibody Formation / Q000187:drug effects; D001483:Base Sequence; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007938:Leukemia / Q000503:physiopathology*; D008832:Microchemistry; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D011948:Receptors, Antigen, T-Cell; D006861:Hydrogen Peroxide; D011494:Protein Kinases; D002118:Calcium