The Mitogen-Induced Increase in T Cell Size Involves PKC and NFAT Activation of Rel/NF-κB-Dependent c-myc Expression

Abstract

Cell growth during the G1 stage of the cell cycle is partly controlled by inducing c-myc expression, which in B cells is regulated by the NF-κB1 and c-Rel transcription factors. Here, we show that c-myc-dependent growth during T cell activation requires c-Rel and RelA and that blocking this growth by inhibiting protein kinase C theta (PKCθ) coincides with a failure to upregulate c-myc due to impaired RelA nuclear import and inhibition of NFAT-dependent c-rel transcription. These results demonstrate that different Rel/NF-κB dimers regulate the mitogenic growth of mature T and B cells, with a signaling pathway incorporating PKCθ and NFAT controlling c-Rel/RelA-induced c-myc expression in activated T cells.