Cell cycling through Cdc25A: transducer of cytokine proliferative signals

Cell Cycle. 2006 May;5(9):907-12. doi: 10.4161/cc.5.9.2693. Epub 2006 May 1.

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 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.

MeSH terms

  • Animals
  • Cell Cycle / physiology*
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / pharmacology
  • Homeostasis
  • Humans
  • Interleukin-7 / pharmacology*
  • Interleukin-7 / physiology
  • Lymphocytes / cytology
  • Lymphocytes / enzymology*
  • Lymphocytes / immunology
  • Mice
  • Models, Biological
  • Signal Transduction / physiology*
  • cdc25 Phosphatases / physiology*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Cytokines
  • Interleukin-7
  • p38 Mitogen-Activated Protein Kinases
  • CDC25A protein, human
  • Cdc25a protein, mouse
  • cdc25 Phosphatases