PKCtheta is necessary for efficient activation of NFkappaB, NFAT, and AP-1 during positive selection of thymocytes.
While it has been shown in several publications that the serine-threonine kinase PKCtheta is required for efficient activation of mature T lymphocytes, the role of PKCtheta in T cell development in the thymus is somewhat controversial. In this study, using knockout mice, we show that PKCtheta is important in positive selection. The thymus of PKCtheta(-/-) animals contains significantly less mature single positive T cells compared to wild-type controls. Biochemically, PKCtheta deficient thymocytes show defective activation of the transcription factors AP-1, NFAT and NFkappaB as well as impaired phosphorylation of the MAP kinase ERK after T cell receptor stimulation in vitro. Together, these results reveal a crucial role of PKCtheta in positive selection of thymocytes in a pathway leading to the activation of ERK, AP-1, NFAT, and NFkappaB.
Gruber
Thomas
T
Department of Medical Genetics, Clinical and Molecular Pharmacology, Medical University of Innsbruck, Schöpfstrasse 41, A-6020 Innsbruck, Austria. thomas.gruber@i-med.ac.at
Pfeifhofer-Obermair
Christa
C
Baier
Gottfried
G
D000818:Animals; D002454:Cell Differentiation; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D018808:Transcription Factor AP-1; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta