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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4109-4116. Prepublished online as a Blood First Edition Paper on September 10, 2008; DOI 10.1182/blood-2008-02-139527. This Article Full Text (PDF) All Versions of this Article: blood-2008-02-139527v1 112/10/4109    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tassi, I. Articles by Colonna, M. Search for Related Content PubMed PubMed Citation Articles by Tassi, I. Articles by Colonna, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 22, 2008 Accepted July 31, 2008 NK cell activating receptors require PKC for sustained signaling, transcriptional activation and IFN- secretion Ilaria Tassi, Marina Cella, Rachel Presti, Angela Colucci, Susan Gilfillan, Dan R Littman, and Marco Colonna* Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, United States Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, United States * Corresponding author; email: mcolonna{at}pathology.wustl.edu. 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 motif (ITAM)-containing adapters, which trigger both cytotoxicy and secretion of interferon-gamma (IFN-). Within the ITAM pathway, distinct signaling intermediates are variably involved in cytotoxicity and/or IFN- secretion. In this study, we have evaluated the role of protein kinase C (PKC) in NK cell secretion of lytic mediators and IFN-. 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- secretion whereas it has no marked influence on the release of cytolytic mediators. Moreover, we found that PKC deficiency preferentially impairs sustained ERK signaling as well as activation of JNK and the transcription factors AP-1 and NFAT, but does not affect activation of NF-B. 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- production. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. I. Aguilo, J. Garaude, J. Pardo, M. Villalba, and A. Anel Protein Kinase C-{theta} Is Required for NK Cell Activation and In Vivo Control of Tumor Progression J. Immunol., February 15, 2009; 182(4): 1972 - 1981. [Abstract] [Full Text] [PDF] D. Kumar, J. Hosse, C. von Toerne, E. Noessner, and P. J. Nelson JNK MAPK Pathway Regulates Constitutive Transcription of CCL5 by Human NK Cells through SP1 J. Immunol., January 15, 2009; 182(2): 1011 - 1020. [Abstract] [Full Text] [PDF]

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