Cell cycling through Cdc25A - Transducer of cytokine proliferative signals

Authors

    Authors

    C. Kittipatarin; W. Q. Li; D. V. Bulavin; S. K. Durum;A. R. Khaled

    Comments

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    Abbreviated Journal Title

    Cell Cycle

    Keywords

    interleukin-7; lymphocyte; p38 MAPK; homeostasis; Cdc25A; cell cycle; p27kip1; growth arrest; proliferation; cytokine; RECEPTOR-DEFICIENT MICE; DEFECTIVE LYMPHOID DEVELOPMENT; DEPENDENT; KINASE INHIBITOR; RESCUES T-LYMPHOPOIESIS; COMMON GAMMA-CHAIN; S-PHASE; CHECKPOINT; IN-VIVO; HOMEOSTATIC PROLIFERATION; INTRACELLULAR PH; CDK; INHIBITORS; Cell Biology

    Abstract

    A balance between survival and proliferative signals maintains a constant number of T lymphocytes that populate the mammalian immune system, a process termed "homeostasis". Central to this process is the availability of a stromal cell product-the cytokine interleukin-7 (IL-7). We recently showed that IL-7, in addition to protecting cells from apoptosis, drives the cell cycling of lymphocytes through regulation of the stability of the phosphatase, Cdc25A, a key activator of cyclin-dependent kinases (cdks). IL-7 achieves this by controlling the activity of p38 MAP kinase (MAPK), which can phosphorylate Cdc25A, triggering its degradation. Sustained expression of Cdc25A had diverse effects: it promoted cell cycling, even in presence of cell cycle inhibitors such p27(Kip1), and prevented cell shrinkage in response to cytokine deprivation. Herein we show a role for Cdc25A as a transducer of cytokine-driven proliferation and discuss novel implications for cell growth from the perspective of the requirements for maintenance of lymphocyte homeostasis.

    Journal Title

    Cell Cycle

    Volume

    5

    Issue/Number

    9

    Publication Date

    1-1-2006

    Document Type

    Article

    Language

    English

    First Page

    907

    Last Page

    912

    WOS Identifier

    WOS:000238575200001

    ISSN

    1538-4101

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