PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes

Z Sun, CW Arendt, W Ellmeier, EM Schaeffer… - Nature, 2000 - nature.com
Z Sun, CW Arendt, W Ellmeier, EM Schaeffer, MJ Sunshine, L Gandhi, J Annes, D Petrzilka…
Nature, 2000nature.com
Productive interaction of a T lymphocyte with an antigen-presenting cell results in the
clustering of the T-cell antigen receptor (TCR) and the recruitment of a large signalling
complex to the site of cell–cell contact,. Subsequent signal transduction resulting in cytokine
gene expression requires the activation of one or more of the multiple isoenzymes of
serine/threonine-specific protein kinase C (PKC). Among the several PKC isoenzymes
expressed in T cells, PKC-θ is unique in being rapidly recruited to the site of TCR clustering …
Abstract
Productive interaction of a T lymphocyte with an antigen-presenting cell results in the clustering of the T-cell antigen receptor (TCR) and the recruitment of a large signalling complex to the site of cell–cell contact,. Subsequent signal transduction resulting in cytokine gene expression requires the activation of one or more of the multiple isoenzymes of serine/threonine-specific protein kinase C (PKC). Among the several PKC isoenzymes expressed in T cells, PKC-θ is unique in being rapidly recruited to the site of TCR clustering. Here we show that PKC-θ is essential for TCR-mediated T-cell activation, but is dispensable during TCR-dependent thymocyte development. TCR-initiated NF-κB activation was absent from PKC-/- mature T lymphocytes, but was intact in thymocytes. Activation of NF-κB by tumour-necrosis factor α and interleukin-1 was unaffected in the mutant mice. Although studies in T-cell lines had suggested that PKC-θ regulates activation of the JNK signalling pathway,, induction of JNK was normal in T cells from mutant mice. These results indicate that PKC-θ functions in a unique pathway that links the TCR signalling complex to the activation of NF-κB in mature T lymphocytes.
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