Cell cycling through Cdc25A - Transducer of cytokine proliferative signals
Abbreviated Journal Title
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
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.
"Cell cycling through Cdc25A - Transducer of cytokine proliferative signals" (2006). Faculty Bibliography 2000s. 6299.