Protein Kinase C theta Affects Ca super(2+) Mobilization and NFAT Cell Activation in Primary Mouse T Cells

Protein kinase C (PKC) theta is an established component of the immunological synapse and has been implicated in the control of AP-1 and NF- Kappa B. To study the physiological function of PKC theta , we used gene targeting to generate a PKC theta null allele in mice. Consistently, interleukin 2 production and T cell proliferative responses were strongly reduced in PKC theta -deficient T cells. Surprisingly, however, we demonstrate that after CD3/CD28 engagement, deficiency of PKC theta primarily abrogates NFAT transactivation. In contrast, NF- Kappa B activation was only partially reduced. This NFAT transactivation defect appears to be secondary to reduced inositol 1,4,5-trisphosphate generation and intracellular Ca super(2+) mobilization. Our finding suggests that PKC theta plays a critical and nonredundant role in T cell receptor-induced NFAT activation.