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 alpha or beta-chain genes by Northern blots. TPA stimulation of an interleukin 2 (IL 2)-producing variant, EL4+, induced a 3-4-fold increase in TCR beta, but not alpha, 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 beta-chain gene and the induction of the IL 2 gene were not linked since expression of TCR beta-chain mRNA was increased to a similar degree in EL4+ and IL 2-nonproducing EL4- sublines, and cyclosporin A selectively blocked TPA-induced IL 2-gene expression in EL4+ cells without affecting the increase in TCR beta-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.
D002460:Cell Line; D003101:Collodion; D004075:Diglycerides / Q000502:physiology; D004587:Electrophoresis, Agar Gel; D004789:Enzyme Activation / Q000187:drug effects*; D005796:Genes / Q000187:drug effects; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000235:genetics*; D013601:T-Lymphocytes / Q000201:enzymology*; D013945:Thymoma; D013997:Time Factors
D004075:Diglycerides; D007376:Interleukin-2; D010703:Phorbol Esters; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D003101:Collodion; D011493:Protein Kinase C