T cell expressed PKCtheta demonstrates cell-type selective function.

Abstract

T lymphocyte stimulation leading to interleukin-2 (IL-2) expression requires activation of protein kinase C (PKC); however, the relevant PKC isoform(s) have not yet been systematically defined. Here we examine seven major T cell expressed PKC isoforms (PKCalpha, delta, epsilon, zeta, nu, theta and iota) and identify PKCtheta to be essential for IL-2 expression (via the critical NF-AT and NF-kappaB enhancer) in Jurkat T cells. Employing a conditionally activated PKCtheta estrogen-receptor fusion mutant, a de novo synthesis-independent transactivation of JNK2 was established. Based on mRNA in situ hybridization to mouse whole body sections, PKCtheta was found to be highly expressed in lymphoid organs but also skeletal muscle and the nervous system. PKCtheta function appears to be cell-type specific, since its isoenzyme-selective function was not observed in ectopic expression studies, employing COS-1 or NIH3T3 cells. These results confirm PKCtheta to be the prime target for the activating effect of phorbol ester in T cell signaling and suggest that gene expression as well as gene function of PKCtheta is strictly controlled by the cell type.