SEARCH:   Advanced

Blood, 1 October 2008, Vol. 112, No. 7, pp. 2869-2877. Prepublished online as a Blood First Edition Paper on July 21, 2008; DOI 10.1182/blood-2007-11-121590. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-11-121590v1 112/7/2869    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Whittaker, G. C. Articles by McVicar, D. W. Search for Related Content PubMed PubMed Citation Articles by Whittaker, G. C. Articles by McVicar, D. W. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Analysis of the linker for activation of T cells and the linker for activation of B cells in natural killer cells reveals a novel signaling cassette, dual usage in ITAM signaling, and influence on development of the Ly49 repertoire Gillian C. Whittaker1, Deborah N. Burshtyn2, Selinda J. Orr1, Laura Quigley1, Deborah L. Hodge1, Véronique Pascal1, Weiguo Zhang3, and Daniel W. McVicar1 1 Cancer and Inflammation Program, National Cancer Institute-Frederick, Frederick MD; 2 Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB; and 3 Department of Immunology, Duke University Medical Center, Durham, NC The linker for activation of T cells (LAT) and the linker for activation of B cells (LAB/NTAL/LAT2) are integral proteins in receptor coupling to downstream events. Both proteins are expressed in natural killer (NK) cells and LAT is phosphorylated during target cell interactions or ligation of the immunoreceptor tyrosine-based activation motif (ITAM)–coupled CD16. Regardless, Lat–/– mice exhibit normal natural and antibody-mediated killing. Here we place both LAT and LAB in the DAP12 pathway of NK cells. Moreover, we unveil a LAT-independent pathway that requires expression of Syk. Mice lacking either LAT or LAB have a skewed Ly49 repertoire, and activated NK cells from Lat–/– mice have reduced responses to the ITAM-coupled receptor NK1.1. In contrast, resting Lat–/– NK cells show intact NK1.1 responses, whereas NK cells without LAB are hyperactive. Elimination of both adaptors severely reduces NK1.1 signaling under both conditions. Together these data show that NK ITAMs preferentially use a signaling cassette regulated by interplay between LAT and LAB. Activation by interleukin-2 causes a shift to greater dependency on LAT due to suppression of Syk signaling. The overlapping use of multiple adaptors permits fine-tuning of NK-cell ITAM responses over the course of an immune response. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020