Protein Kinase C θ Affects Ca2+ Mobilization and NFAT Activation in Primary Mouse T Cells
C Pfeifhofer, K Kofler, T Gruber… - The Journal of …, 2003 - rupress.org
The Journal of experimental medicine, 2003•rupress.org
Protein kinase C (PKC) θ is an established component of the immunological synapse and
has been implicated in the control of AP-1 and NF-κB. To study the physiological function of
PKCθ, we used gene targeting to generate a PKCθ null allele in mice. Consistently,
interleukin 2 production and T cell proliferative responses were strongly reduced in PKCθ-
deficient T cells. Surprisingly, however, we demonstrate that after CD3/CD28 engagement,
deficiency of PKCθ primarily abrogates NFAT transactivation. In contrast, NF-κB activation …
has been implicated in the control of AP-1 and NF-κB. To study the physiological function of
PKCθ, we used gene targeting to generate a PKCθ null allele in mice. Consistently,
interleukin 2 production and T cell proliferative responses were strongly reduced in PKCθ-
deficient T cells. Surprisingly, however, we demonstrate that after CD3/CD28 engagement,
deficiency of PKCθ primarily abrogates NFAT transactivation. In contrast, NF-κB activation …
Protein kinase C (PKC)θ is an established component of the immunological synapse and has been implicated in the control of AP-1 and NF-κB. To study the physiological function of PKCθ, we used gene targeting to generate a PKCθ null allele in mice. Consistently, interleukin 2 production and T cell proliferative responses were strongly reduced in PKCθ-deficient T cells. Surprisingly, however, we demonstrate that after CD3/CD28 engagement, deficiency of PKCθ primarily abrogates NFAT transactivation. In contrast, NF-κB activation was only partially reduced. This NFAT transactivation defect appears to be secondary to reduced inositol 1,4,5-trisphosphate generation and intracellular Ca2+ mobilization. Our finding suggests that PKCθ plays a critical and nonredundant role in T cell receptor–induced NFAT activation.
rupress.org
