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    DAP12 impacts trafficking and surface stability of killer cell immunoglobulin-like receptors on natural killer cells

    Cover for DAP12 impacts trafficking and surface stability of killer cell immunoglobulin-like receptors on natural killer cells
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    View/Open: Mulrooney_georgetown_0076D_11934.pdf (1.6MB) Bookview

    Creator
    Mulrooney, Tiernan
    Advisor
    Hurley, Carolyn
    Abstract
    Killer cell immunoglobulin-like receptors (KIR) aid in the regulation of natural killer (NK) cell activity. In this study, the effect of the interaction between the two domain stimulatory KIR (KIR2DS) and their adapter, DAP12, was investigated beyond the previously defined signaling function. Flow cytometry analysis showed enhanced KIR2DS surface expression on NKL cells when co-transfected with DAP12. Conversely, KIR2DS4 surface expression on primary cells was decreased when the cells were treated with DAP12 specific siRNA. Treatment of the KIR2DS and DAP12 transfected cells with either cycloheximide or brefeldin A repressed KIR2DS surface expression revealing a role for DAP12 in trafficking newly synthesized KIR to the cell surface. Immunoprecipitation of DAP12 revealed an interaction of DAP12 with an immature isoform of KIR2DS indicating the interaction between these proteins initiates early in the maturation process, likely within the endoplasmic reticulum. An internalization assay demonstrated a significant impact of DAP12 on KIR2DS surface stability. Confocal microscopy showed internalized KIR2DS molecules are recruited to lysosomal compartments independent of DAP12 expression. Our results suggest in vivo conditions that adversely affect DAP12 expression will indirectly reduce surface expression and stability of KIR2DS. These effects could significantly impact ligand recognition and strength of signaling through KIR2DS molecules.
    Description
    Ph.D.
    Permanent Link
    http://hdl.handle.net/10822/557908
    Date Published
    2012
    Subject
    Immunology; Molecular biology; Oncology; Immunology; Molecular biology; Oncology;
    Type
    thesis
    Publisher
    Georgetown University
    Extent
    115 leaves
    Collections
    • Graduate Theses and Dissertations - Tumor Biology
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    Georgetown University Seal
    ©2009 - 2022 Georgetown University Library
    37th & O Streets NW
    Washington DC 20057-1174
    202.687.7385
    digitalscholarship@georgetown.edu
    Accessibility