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-θ(-/-) mature T lymphocytes, but was intact in thymocytes. Activation of NF-κB by tumour- necrosis factor a 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.
Original language | English (US) |
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Pages (from-to) | 402-407 |
Number of pages | 6 |
Journal | Nature |
Volume | 404 |
Issue number | 6776 |
DOIs | |
State | Published - Mar 23 2000 |
ASJC Scopus subject areas
- General