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    Engaging Ly‐6A/Sca‐1 triggers lipid raft‐dependent and ‐independent responses in CD4+ T‐cell lines

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    Author
    Lang, M.A.
    Jenkins, S.A.
    Balzano, P.
    Date
    2017
    Journal
    Immunity Inflammation and Disease
    Publisher
    Wiley-Blackwell
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://www.doi.org/10.1002/iid3.182
    Abstract
    Introduction: The lymphocyte antigen 6 (Ly-6) supergene family encodes proteins of 12-14 kda in molecular mass that are either secreted or anchored to the plasma membrane through a glycosyl-phosphatidylinisotol (GPI) lipid anchor at the carboxy-terminus. The lipidated GPI-anchor allows localization of Ly-6 proteins to the 10-100 nm cholesterol-rich nano-domains on the membrane, also known as lipid rafts. Ly-6A/Sca-1, a member of Ly-6 gene family is known to transduce signals despite the absence of transmembrane and cytoplasmic domains. It is hypothesized that the localization of Ly-6A/Sca-1 with in lipid rafts allows this protein to transduce signals to the cell interior. Methods and Results: In this study, we found that cross-linking mouse Ly-6A/Sca-1 protein with a monoclonal antibody results in functionally distinct responses that occur simultaneously. Ly-6A/Sca-1 triggered a cell stimulatory response as gauged by cytokine production with a concurrent inhibitory response as indicated by growth inhibition and apoptosis. While production of interleukin 2 (IL-2) cytokine by CD4+ T cell line in response to cross-linking Ly-6A/Sca-1 was dependent on the integrity of lipid rafts, the observed cell death occurred independently of it. Growth inhibited CD4+ T cells showed up-regulated expression of the inhibitory cell cycle protein p27kip but not of p53. In addition, Ly-6A/Sca-1 induced translocation of cytochrome C to the cytoplasmalong with activated caspase 3 and caspase 9, thereby suggesting an intrinsic apoptotic cell death mechanism. Conclusions: We conclude that opposing responses with differential dependence on the integrity of lipid rafts are triggered by engaging Ly-6A/Sca-1 protein on the membrane of transformed CD4+ T cells. Copyright 2017 The Authors.
    Sponsors
    This work was supported by SRFG & SRG grants from Office of Research and Sponsored Projects (ORSP), Villanova University and Department of Biology, Villanova University.
    Keyword
    Apoptosis
    Cd4+ T cells
    Cell cycle
    GPI-anchored
    Lipid raft
    Ly-6A
    Membrane order
    Sca-1
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85040759563&doi=10.1002%2fiid3.182&partnerID=40&md5=59c891b36fb672a7ab39eda28da7761f; http://hdl.handle.net/10713/10019
    ae974a485f413a2113503eed53cd6c53
    10.1002/iid3.182
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