Naoko Arai

T Cell Activation Signals and Regulation of Lymphokine Gene by Viral and Cellular Transactivators

T cells activated by antigen stimulation produce a set of lymphokines. By employing protein kinase C (PKC) which is active without stimulation or viral transactivator HTLV-I p40tax or BPV E2 protein, we characterized the T cell antigen receptor signal transduction pathway downstream of PKC. Consistent with the earlier observations that activation of PKC and Ca2+ influx are necessary for T cell activation, the IL-2 promoter is activated by actions of constitutively active PKC and Ca2+ ionophore in the human T cell leukemia line Jurkat. We found that p40tax or E2 protein activate transfected GM-CSF gene as well as SV40 and HIV promoters without external stimuli. The sequence of GM-CSF promoter required for stimulation by PMA/A23187 is localized between positions -95 and -73 (CLE2). The same region responds to p40tax or E2 protein. Another sequence, located between -113 and -96 (CLE1), mediates inducible response to p40tax but not to E2 protein or PMA/A23187 stimulation. Activation of the SV40 promoter by p40tax or E2 protein is dependent on SV40 enhancer sequences. Only one copy of the segment carrying the NF-κ B binding site is sufficient to mediate the induction by E2 protein, p40tax or PMA/A23187 stimulation. HIV LTR promoter also responds to E2 protein or p40tax through the same DNA element. These results indicate that p40tax or E2 protein activate GM-CSF and viral promoters by interacting with cellular component(s) in the T cell activation signal transduction pathway.