The Tpl-2 protooncoprotein activates the nuclear factor of activated T cells and induces interleukin 2 expression in T cell lines

Tpl-2 expression is induced within 30-60 min after ConA stimulation of rat splenocytes, suggesting that it may contribute to the induction of IL-2 during T cell activation, Herein we show that wild-type and carboxyl-terminally truncated (activated) Tpl-2 activate the nuclear factor of activated T cells (NEAT) and induce interleukin 2 (IL-2) expression in EL4 cells, In Jurkat cells the truncated Tpl-2 activates NEAT and induces IL-2, whereas wild-type Tpl-2 activates NFAT only when cotransfected with NEAT expression constructs, suggesting that Tpl-2 may induce NFAT activation signals, Experiments in NIH 3T3 cells revealed that the NFATp isoform, but not the NFATc or NFATx isoform, undergoes nuclear translocation when coexpressed with wildtype Tpl-2 and confirmed this hypothesis, Activation of NEAT by anti-CD3 stimulation but not by phorbol 12-myristate 13-acetate and ionomycin in Jurkat cells was inhibited by the kinase-dead Tpl-2K167M, suggesting that Tpl-2 contributes to the transduction of NEAT activation signals originating in the T cell receptor, The Tpl-2-mediated induction of IL-2 was not observed in T cell lymphoma lines other than EL3 and Jurkat, as well as in normal T cells, NFAT activation by Tpl-2, however, was observed in several cell lines including some of nonhematopoietic origin, The activation of NFAT by Tpl-2 in different cell types defines a molecular mechanism that may contribute to its oncogenic potential.