PKC-theta is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes.

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.

• Authors: Z Sun, C W Arendt, W Ellmeier, E M Schaeffer, M J Sunshine, L Gandhi, J Annes, D Petrzilka, A Kupfer, P L Schwartzberg, D R Littman
• Journal: Nature (Nature) Vol. 404 Issue 6776 Pg. 402-7 (Mar 23 2000) ISSN: 0028-0836 [Print] England
• PMID: 10746729 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 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

Topics

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