Back to Search
Start Over
NK cell-activating receptors require PKC-theta for sustained signaling, transcriptional activation, and IFN-gamma secretion.
- Source :
-
Blood [Blood] 2008 Nov 15; Vol. 112 (10), pp. 4109-16. Date of Electronic Publication: 2008 Sep 10. - Publication Year :
- 2008
-
Abstract
- Natural killer (NK) cell sense virally infected cells and tumor cells through multiple cell surface receptors. Many NK cell-activating receptors signal through immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters, which trigger both cytotoxicy and secretion of interferon-gamma (IFN-gamma). Within the ITAM pathway, distinct signaling intermediates are variably involved in cytotoxicity and/or IFN-gamma secretion. In this study, we have evaluated the role of protein kinase C- (PKC-) in NK-cell secretion of lytic mediators and IFN-gamma. We found that engagement of NK-cell receptors that signal through ITAMs results in prompt activation of PKC-. Analyses of NK cells from PKC--deficient mice indicated that PKC- is absolutely required for ITAM-mediated IFN-gamma secretion, whereas it has no marked influence on the release of cytolytic mediators. Moreover, we found that PKC- deficiency preferentially impairs sustained extracellular-regulated kinase signaling as well as activation of c-Jun N-terminal kinase and the transcription factors AP-1 and NFAT but does not affect activation of NF-kappaB. These results indicate that NK cell-activating receptors require PKC- to generate sustained intracellular signals that reach the nucleus and promote transcriptional activation, ultimately inducing IFN-gamma production.
- Subjects :
- Animals
Interferon-gamma immunology
Isoenzymes genetics
Isoenzymes immunology
JNK Mitogen-Activated Protein Kinases immunology
JNK Mitogen-Activated Protein Kinases metabolism
Killer Cells, Natural immunology
Mice
Mice, Knockout
NF-kappa B immunology
NF-kappa B metabolism
NFATC Transcription Factors immunology
NFATC Transcription Factors metabolism
Protein Kinase C genetics
Protein Kinase C immunology
Protein Kinase C-theta
Transcription Factor AP-1 immunology
Transcription Factor AP-1 metabolism
Interferon-gamma metabolism
Isoenzymes metabolism
Killer Cells, Natural enzymology
Protein Kinase C metabolism
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 112
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 18784374
- Full Text :
- https://doi.org/10.1182/blood-2008-02-139527