PKC-theta Is Required for TCR-induced NF-kappaB Activation in Mature but Not Immature T Lymphocytes

Nature. 2000 Mar 23;404(6776):402-7. doi: 10.1038/35006090.

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-theta is unique in being rapidly recruited to the site of TCR clustering. Here we show that PKC-theta is essential for TCR-mediated T-cell activation, but is dispensable during TCR-dependent thymocyte development. TCR-initiated NF-kappaB activation was absent from PKC-theta(-/-) mature T lymphocytes, but was intact in thymocytes. Activation of NF-kappaB by tumour-necrosis factor alpha and interleukin-1 was unaffected in the mutant mice. Although studies in T-cell lines had suggested that PKC-theta regulates activation of the JNK signalling pathway, induction of JNK was normal in T cells from mutant mice. These results indicate that PKC-theta functions in a unique pathway that links the TCR signalling complex to the activation of NF-kappaB in mature T lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Female
  • Hemocyanins / immunology
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Leukopoiesis
  • Lymphocyte Activation*
  • Male
  • Mice
  • Mutagenesis
  • NF-kappa B / physiology*
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology

Substances

  • Antigens, CD
  • Isoenzymes
  • NF-kappa B
  • Receptors, Antigen, T-Cell
  • Hemocyanins
  • PRKCQ protein, human
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta
  • keyhole-limpet hemocyanin