Protein kinase C theta affects Ca2+ 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-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 Ca2+ mobilization. Our finding suggests that PKCtheta plays a critical and nonredundant role in T cell receptor-induced NFAT activation.
Pfeifhofer
Christa
C
Institute of Medical Biology and Human Genetics, University of Innsbruck, Schoepfstrasse 41, A-6020 Innsbruck, Austria.
Kofler
Kurt
K
Gruber
Thomas
T
Tabrizi
Nassim Ghaffari
NG
Lutz
Christina
C
Maly
Karl
K
Leitges
Michael
M
Baier
Gottfried
G
D000818:Animals; D001483:Base Sequence; D020013:Calcium Signaling; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D007527:Isoenzymes; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D014157:Transcription Factors; D004247:DNA; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta