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

Zuoming Sun, Christopher W. Arendt, Wilfried Ellmeier, Edward M. Schaeffer, Mary Jean Sunshine, Leena Gandhl, Justin Annes, Danlela Petrzilka, Abraham Kupfer, Pamela L. Schwartzberg, Dan R. Littman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

776 Scopus citations

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 languageEnglish (US)
Pages (from-to)402-407
Number of pages6
JournalNature
Volume404
Issue number6776
DOIs
StatePublished - Mar 23 2000

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes'. Together they form a unique fingerprint.

Cite this