Differential expression of protein kinase C isoenzymes related to high nitric oxide synthase activity in a T lymphoma cell line

Abstract

Protein kinase C (PKC) is critical for T lymphocyte activation and proliferation, while nitric oxide synthase (NOS) may function both as an activator or inhibitor of T cell apoptosis. Both enzymatic activities were studied in T lymphoma cells in comparison to normal and activated T lymphocytes. Here we show a higher translocation of PKC in BW5147 lymphoma cells than in mitogen-stimulated T lymphocytes. Tumor cells overexpressed PKC ζ isoform, while high levels of the PKC β isotype were found in mitogen-stimulated T lymphocytes. Moreover, tumoral T cells showed high NOS activity, almost undetectable in normal or stimulated T lymphocytes. PKC and NOS inhibitors or the intracellular delivery of an anti-PKC ζ antibody diminished both NO production and proliferation in tumor cells. These results suggest that atypical PKC ζ isoform expression and its association with NOS activity regulation would participate in the multistep process leading to BW5147 cell malignant transformation.