Browsing by Subject "Phosphoric Monoester Hydrolases"

Now showing 1 - 3 of 3
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    Phosphatase of regenerating liver in hematopoietic stem cells and hematological malignancies
    (Landes Bioscience, 2014) Kobayashi, Michihiro; Chen, Sisi; Gao, Rui; Bai, Yunpeng; Zhang, Zhong-Yin; Liu, Yan; Department of Pediatrics, IU School of Medicine
    The phosphatases of regenerating liver (PRLs), consisting PRL1, PRL2 and PRL3, are dual-specificity protein phosphatases that have been implicated as biomarkers and therapeutic targets in several solid tumors. However, their roles in hematological malignancies are largely unknown. Recent findings demonstrate that PRL2 is important for hematopoietic stem cell self-renewal and proliferation. In addition, both PRL2 and PRL3 are highly expressed in some hematological malignancies, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), multiple myeloma (MM) and acute lymphoblastic leukemia (ALL). Moreover, PRL deficiency impairs the proliferation and survival of leukemia cells through regulating oncogenic signaling pathways. While PRLs are potential novel therapeutic targets in hematological malignancies, their exact biological function and cellular substrates remain unclear. This review will discuss how PRLs regulate hematopoietic stem cell behavior, what signaling pathways are regulated by PRLs, and how to target PRLs in hematological malignancies. An improved understanding of how PRLs function and how they are regulated may facilitate the development of PRL inhibitors that are effective in cancer treatment.
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    The role of SHIP in the development and activation of mouse mucosal and connective tissue mast cells
    (The American Association of Immunologists, 2012-04-15) Ruschmann, Jens; Antignano, Frann; Lam, Vivian; Snyder, Kim; Kim, Connie; Essak, Martha; Zhang, Angela; Lin, Ann Hsu-An; Mali, Raghuveer Singh; Kapur, Reuben; Krystal, Gerald; Department of Pediatrics, IU School of Medicine
    Although SHIP is a well-established suppressor of IgE plus Ag-induced degranulation and cytokine production in bone marrow-derived mast cells (BMMCs), little is known about its role in connective tissue (CTMCs) or mucosal (MMCs) mast cells. In this study, we compared SHIP's role in the development as well as the IgE plus Ag and TLR-induced activation of CTMCs, MMCs, and BMMCs and found that SHIP delays the maturation of all three mast cell subsets and, surprisingly, that it is a positive regulator of IgE-induced BMMC survival. We also found that SHIP represses IgE plus Ag-induced degranulation of all three mast cell subsets and that TLR agonists do not trigger their degranulation, whether SHIP is present or not, nor do they enhance IgE plus Ag-induced degranulation. In terms of cytokine production, we found that in MMCs and BMMCs, which are poor producers of TLR-induced cytokines, SHIP is a potent negative regulator of IgE plus Ag-induced IL-6 and TNF-α production. Surprisingly, however, in splenic or peritoneal derived CTMCs, which are poor producers of IgE plus Ag-induced cytokines, SHIP is a potent positive regulator of TLR-induced cytokine production. Lastly, cell signaling and cytokine production studies with and without LY294002, wortmannin, and PI3Kα inhibitor-2, as well as with PI3K p85α(-/-) BMMCs and CTMCs, are consistent with SHIP positively regulating TLR-induced cytokine production via an adaptor-mediated pathway while negatively regulating IgE plus Ag-induced cytokine production by repressing the PI3K pathway.
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    SCP4: A Small Nuclear Phosphatase Having a Big Effect on FoxOs in Gluconeogenesis
    (American Diabetes Association, 2018-01) Dong, X. Charlie; Biochemistry and Molecular Biology, School of Medicine