Differential activation of PKC isozymes by 14-3-3 zeta protein

14-3-3 proteins are ubiquitous in eukaryotes associated with many fundamental functions in signal transduction pathways and cell cycle regulation. Protein kinase C comprises a large family of serine/threonine protein kinases that are involved in cell growth and differentiation. Different protein kinase C isozymes have distinct roles in signal transduction pathways; protein kinase C epsilon is of particular interest because its overexpression leads to oncogenic transformation. The 14-3-3 protein has been reported to regulate the activity of protein kinase C, although the nature of its effect is equivocal. In this study we report the differential activation of various protein kinase C isoforms by 14-3-3 zeta protein. The classical isozymes show approximately a twofold activation, protein kinase C delta shows no significant increase in activity, whereas protein kinase C epsilon, another novel isozyme, is highly activated. This activation shows strong positive cooperativity with a Hill coefficient of 6.1 +/- 0.2.