A comparative analysis of protein kinase C-theta (PKC theta) protein expression was performed in various mouse organs and tissues, freshly isolated populations of mouse and human hematopoietic cells, primary leukemias, and established cell lines of different histological origins. Results demonstrated a predominant expression of PHC theta in lymphoid tissues and skeletal muscle. Expression levels of PKC theta, as well as PKC alpha, delta, epsilon, zeta, and eta in the thymus, were not markedly changed during postnatal development. High levels of expression were observed in CD4(+) and CD8(+) single-positive T cells and CD4(+)CD8(+) double-positive thymocytes, while B cells were completely devoid of PRC theta. PKC theta was found also in platelets, but relatively low levels or no detection of PKC theta expression were observed in neutrophils, monocytes, and macrophages. Highly proliferating leukemic T cells of established lines or primary tumors, but not freshly isolated resting peripheral blood T cells, exhibited high levels of membrane-bound PKC theta. Increased proportions of PKC theta in the particulate fraction was not restricted to malignant cells but correlated with the extent of proliferation of the T cells. Thus, human peripheral blood T cells that were induced to proliferate by exposure to mitogen and IL-2 expressed increased levels of PKC theta in the particulate fraction. Significantly lower proportions of membrane-bound PKC were observed for five other isoenzymes expressed in T cells. The occurrence of PKC theta in T, but not B, cells and its subcellular distribution in proliferating cells implicate PKC theta in cellular mechanisms regulating the sustained proliferation of T cells. (C) 1999 Academic Press.