Cell cycling through Cdc25A: transducer of cytokine proliferative signals.
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 p27Kip1, 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.
Kittipatarin
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C
BioMolecular Science Center, University of Central Florida, Orlando, Florida 32826, USA.
Li
W Q
WQ
Bulavin
D V
DV
Durum
S K
SK
Khaled
A R
AR
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology* / Q000502:physiology; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*; D020687:cdc25 Phosphatases / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016207:Cytokines; D015851:Interleukin-7; D048051:p38 Mitogen-Activated Protein Kinases; C517004:CDC25A protein, human; C517005:Cdc25a protein, mouse; D020687:cdc25 Phosphatases