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

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 zeta isoform, while high levels of the PKC beta 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 zeta antibody diminished both NO production and proliferation in tumor cells. These results suggest that atypical PKC zeta isoform expression and its association with NOS activity regulation would participate in the multistep process leading to BW5147 cell malignant transformation.