PKCθ is necessary for efficient activation of NFκB, NFAT, and AP-1 during positive selection of thymocytes

While it has been shown in several publications that the serine-threonine kinase PKC theta is required for efficient activation of mature T lymphocytes, the role of PKC theta in T cell development in the thymus is somewhat controversial. In this study, using knockout mice, we show that PKC theta is important in positive selection. The thymus of PKC theta(-/-) animals contains significantly less mature single positive T cells compared to wild-type controls. Biochemically, PKC theta deficient thymocytes show defective activation of the transcription factors AP-1, NFAT and NF kappa B 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 PKC theta in positive selection of thymocytes in a pathway leading to the activation of ERR, AP-1, NFAT, and NF kappa B. (C) 2010 Elsevier B.V. All rights reserved.