Protein kinase C‐activating phorbol esters augment expression of T cell receptor genes

Tumor‐promoting phorbol esters (PE) can modulate cellular functions and cell surface determinant expression in a variety of cell types, including T lymphocytes, presumably by activating the enzyme, protein kinase C (PKC). To examine whether PKC might be involved in regulating the expression of genes encoding the antigen‐specific T cell receptor (TCR), we cultured the murine thymoma line, EL4, in the presence of 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) and analyzed the expression of TCR α or β‐chain genes by Northern blots. TPA stimulation of an interleukin 2 (IL 2)‐producing variant, EL4⁺, induced a 3–4‐fold increase in TCR β, but not α, chain mRNA. Maximal increase was obtained with 3 ng/ml TPA and 12 h of stimulation. This effect appeared related to PKC activation because other tumor‐promoting PE known to be PKC activators, but not inactive PE, induced the same increase. TPA stimulation of EL4⁺ cells also induced de novo expression of the IL 2 gene and subsequent secretion of this lymphokine. However, the increased expression of the TCR β‐chain gene and the induction of the IL 2 gene were not linked since (a) expression of TCR β‐chain mRNA was increased to a similar degree in EL4⁺ and IL 2‐nonproducing EL4⁻ sublines, and (b) cyclosporin A selectively blocked TPA‐induced IL 2‐gene expression in EL4⁺ cells without affecting the increase in TCR β‐chain mRNA. These findings suggest that PKC activation, an event that supposedly occurs after antigen‐mediated triggering of the TCR, can regulate the expression of at least some of the genes encoding this receptor.