PKC-theta is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes.
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.
Sun
Z
Z
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York 10016, USA.
Arendt
C W
CW
Ellmeier
W
W
Schaeffer
E M
EM
Sunshine
M J
MJ
Gandhi
L
L
Annes
J
J
Petrzilka
D
D
Kupfer
A
A
Schwartzberg
P L
PL
Littman
D R
DR
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D019891:Leukopoiesis; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D016296:Mutagenesis; D016328:NF-kappa B / Q000502:physiology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D015703:Antigens, CD; D007527:Isoenzymes; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D006433:Hemocyanins; C076233:PRKCQ protein, human; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; C032808:keyhole-limpet hemocyanin