Protein kinase C θ affects Ca2+ mobilization and NFAT cell activation in primary mouse T cells

被引:284
作者
Pfeifhofer, C
Kofler, K
Gruber, T
Tabriz, NG
Lutz, C
Maly, K
Leitges, M
Baier, G
机构
[1] Univ Innsbruck, Inst Med Biol & Human Genet, A-6020 Innsbruck, Austria
[2] Univ Innsbruck, Inst Med Biochem, A-6020 Innsbruck, Austria
[3] Max Planck Inst Expt Endocrinol, D-30625 Hannover, Germany
关键词
T lymphocyte; PKC theta; TCR/CD3; Ca(2+) response; NFAT;
D O I
10.1084/jem.20020234
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-kappaB. To study the physiological function of PKCtheta, we used gene targeting to generate a PKCtheta null allele in mice. Consistently, interleukin 2 production and T cell proliferative responses were strongly reduced in PKCtheta-deficient T cells. Surprisingly, however, we demonstrate that after CD3/CD28 engagement, deficiency of PKCtheta primarily abrogates NFAT transactivation. In contrast, NF-kappaB activation was only partially reduced. This NFAT transactivation defect appears to be secondary to reduced inositol 1,4,5-trisphosphate generation and intracellular Ca(2+) mobilization. Our finding suggests that PKCtheta plays a critical and nonredundant role in T cell receptor-induced NFAT activation.
引用
收藏
页码:1525 / 1535
页数:11
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